Conditions: Diabetes Mellitus, Type 2
Keywords: Pharmacodynamics Safety Albiglutide Tolerability Type 2 Diabetes Mellitus Efficacy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 308
Healthy volunteers: no

Brief summary:
This is a phase III, randomized, double-blind, multicenter, parallel group, repeat-dose, study of 26 weeks duration to evaluate the efficacy, safety, tolerability and pharmacodynamic response of albiglutide liquid drug product relative to the commercial lyophilized drug product. The study will specifically evaluate the potential for immunogenicity (example \[e.g.\] incidences of anti-drug antibodies \[ADA\]) and injection site reactions (ISRs).

Albiglutide is a novel analogue of glucagon-like peptide-1 (GLP-1) with a sufficiently long half-life to permit once a week injection. Currently, lyophilized albiglutide and the diluent are provided in a dual chamber cartridge (DCC), single-dose pen injector, requiring reconstitution prior to use. A liquid formulation of albiglutide will enable the commercialization of a liquid product in a single dose, ready-to-use prefilled syringe in an auto-injector.

The primary hypothesis of this study is to test that liquid drug product will provide glycemic control (as measured by HbA1c change from baseline) non-inferior to lyophilized drug product for a period of 26 weeks of treatment in subjects with T2DM.

This study will comprise of 3 study periods : screening (2 weeks), treatment (26 weeks) and for those subjects not entering the extension study a follow-up period (8 weeks). Approximately 300 subjects will be randomized in a 1:1 ratio to either Albiglutide active liquid auto-injector (LAI) plus Placebo lyophilized DCC pen injector (lyophilized DCC PI); or, Albiglutide lyophilized DCC PI plus Placebo LAI.

Detailed description:

Arms:
arm 1: Subjects will receive 30 milligrams (mg) of albiglutide liquid drug product via auto injector and matching placebo via lyophilized DCC pen injector for 4 weeks. The dose will then be up-titrated to 50mg albiglutide for the remaining 22 weeks of the study. The study treatment will be administered once weekly by subcutaneous injection in the abdomen, thigh, or upper arm. arm 2: Subjects will receive 30mg of albiglutide lyophilized drug product via DCC pen injector and matching placebo via auto injector for 4 weeks. The dose will then be up-titrated to 50mg albiglutide for the remaining 22 weeks of the study. The study treatment will be administered once weekly by subcutaneous injection in the abdomen, thigh, or upper arm.

Interventions: intervention 1: Lyophilized albiglutide DCC pen injector intervention 2: Lyophilized albiglutide DCC pen injector matching placebo intervention 3: Albiglutide liquid auto-injector intervention 4: Albiglutide liquid auto-injector matching placebo
Intervention descriptions: intervention 1: A fixed-dose, fully disposable pen injector system with a prefilled dual chamber glass cartridge (DCC) containing lyophilized albiglutide (30mg or 50mg) delivering an injection volume of 0.5mL. intervention 2: A fixed-dose, fully disposable pen injector system with a prefilled DCC containing matching placebo delivering an injection volume of 0.5mL intervention 3: A fixed-dose, single use, disposable auto-injector containing albiglutide liquid (30mg or 50mg) in a prefilled glass syringe. The auto-injector delivers the albiglutide liquid in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose. intervention 4: A fixed-dose, single use, disposable auto-injector containing matching placebo in a prefilled glass syringe. The auto-injector delivers the matching placebo in an injection volume of 0.6 mL for the 30mg dose and 1.0 mL for the 50mg dose.

Protocol document:
Prot_000.pdf: 
2014N210004_02
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The GlaxoSmithKline group of companies
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TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
A Repeat-dose Study in Subjects with Type 2 Diabetes Mellitus 
to Assess the Efficacy, Safety, Tolerability and 
Pharmacodynamics, of Albiglutide Liquid Drug Product
Compound Number:
GSK716155
Development Phase:
III
Effective Date:
26-MAY-2016
Protocol Amendment Number:  02
Author (s):
 
Copyright 2016 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD


2014N210004_02
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Revision Chronology
GlaxoSmithKline
Document Number
Date
Version
2014N210004_00
2015-OCT-28
Original
2014N210004_01
2016-MAR-23
Amendment No. 1
Benefit risk table modified to provide further details relating to mitigation strategies.
New text to clarify visit windows.
Exclusion criteria related to abnormal TSH modified.
Exclusion criteria numbering corrected. 
Exclusion criteria relating to positive urine drug screen result at Screening modified.
Time and Event Table modified to add HbA1c sample at Week 12
Time and Event Table modified to remove the Week 13 PK sample and add a PK sample 
at Week 12.
Details for collection of PK samples moved to SPM.
Timings for handling of missing data changed.
2014N210004_02
2016-MAY-26
Amendment No. 2
Protocol modified to allow subjects who discontinue investigational product to be
followed for safety and efficacy unless the subject is “lost to follow-up” or withdraws 
consent.
Minor updates to benefit risk table 
Clarification in inclusion criteria that those subjects on a stable dose of metforim must be 
receiving metformin as monotherapy.
Exclusion criteria relating to use of dipeptidyl peptidase-IV inhibitors updated to include 
GLP 1 receptor agonists and other antidiabetic medications.
Clarification of metformin dose adjustment.
Text relating to prohibited medications modified to provide details on dipeptidyl 
peptidase-IV inhibitors, GLP 1 receptor agonists and other antidiabetic medications.
Addition of visit windows to Time and Events Table.
Footnotes to Time and Events Table updated
Modifications made to the primary analysis, secondary analyses, supportive primary 
analyses, impact of missing data on primary analysis, and sensitivity analysis.


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Minor typographical errors


PPD
PPD


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MEDICAL MONITOR/SPONSOR INFORMATION PAGE
Medical Monitor/SAE Contact Information: 
Role
Name
Day Time Phone 
Number and email 
address
After-hours 
Phone/Cell/
Pager Number
Fax 
Number
Site 
Address
Primary Medical 
Monitor 
MD
PPD 
Pharmacovigilance
24-hour Safety 
Hotline
Email – N/A
24-hour Safety 
Hotline
N/A
Secondary 
Medical Monitor
MD
PPD 
Pharmacovigilance
24-hour Safety 
Hotline
Email – N/A
24-hour Safety 
Hotline
N/A
SAE Coordinator
PPD 
Pharmacovigilance
North America
24-hour Safety 
Hotline
24-hour Safety 
Hotline
N/A
FAX number for 
SAE reporting
Sponsor Legal Registered Address: 
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
PPD is the contract research organization for this study
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline Affiliate 
Company (or designee). If applicable, the details of the alternative Sponsor and contact 
person in the territory will be provided to the relevant regulatory authority as part of the 
clinical trial application.   
Regulatory Agency Identifying Number(s):  US IND 124228
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


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INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol number 2014N210004_02
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
Investigator Name:
Investigator Address:
Investigator Phone Number:
Investigator Signature
Date


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TABLE OF CONTENTS
PAGE
1.
PROTOCOL SYNOPSIS FOR STUDY 200952......................................................10
2.
INTRODUCTION....................................................................................................13
2.1.
Study Rationale ..........................................................................................13
2.2.
Brief Background ........................................................................................13
3.
OBJECTIVE(S) AND ENDPOINT(S) ......................................................................15
4.
STUDY DESIGN ....................................................................................................15
4.1.
Overall Design ............................................................................................15
4.2.
Treatment Arms and Duration.....................................................................16
4.3.
Type and Number of Subjects.....................................................................17
4.4.
Design Justification.....................................................................................17
4.5.
Dose Justification........................................................................................18
4.6.
Benefit:Risk Assessment ............................................................................18
4.6.1.
Risk Assessment .........................................................................19
4.6.2.
Benefit Assessment.....................................................................27
4.6.3.
Overall Benefit: Risk Conclusion..................................................27
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA .............28
5.1.
Inclusion Criteria.........................................................................................28
5.2.
Exclusion Criteria........................................................................................29
5.3.
Screening/Baseline/Run-in Failures............................................................32
5.4.
Hyperglycemia Rescue...............................................................................32
5.5.
Withdrawal/Stopping Criteria.......................................................................33
5.5.1.
Permanent Discontinuation of Investigational Product .................33
5.5.1.1.
Procedures for Subject Follow-up Following 
Discontinuation of Investigational Product ..................34
5.5.2.
Subjects Who Fail to Attend Clinic Visits......................................34
5.5.3.
Withdrawal from Study.................................................................35
5.5.4.
Liver Chemistry Stopping Criteria ................................................35
5.5.4.1.
Study Treatment Restart or Rechallenge....................36
5.5.5.
QTc Stopping Criteria ..................................................................36
5.6.
Subject and Study Completion....................................................................37
6.
STUDY TREATMENT ............................................................................................37
6.1.
Investigational Product and Other Study Treatment....................................37
6.2.
Treatment Assignment................................................................................40
6.3.
Planned Dose Adjustments.........................................................................40
6.4.
Blinding.......................................................................................................40
6.5.
Packaging and Labeling..............................................................................41
6.6.
Preparation/Handling/Storage/Accountability..............................................41
6.7.
Compliance with Study Treatment Administration.......................................42
6.8.
Treatment of Study Treatment Overdose....................................................42
6.9.
Treatment after the End of the Study ..........................................................42
6.10.
Concomitant Medications and Non-Drug Therapies....................................43
6.10.1.
Permitted Medications and Non-Drug Therapies..........................43
6.10.2.
Prohibited Medications and Non-Drug Therapies.........................43


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7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................45
7.1.
Time and Events.........................................................................................46
7.2.
Screening and Critical Baseline Assessments ............................................50
7.3.
Efficacy.......................................................................................................50
7.4.
Safety .........................................................................................................50
7.4.1.
Adverse Events (AE) and Serious Adverse Events (SAEs)..........50
7.4.1.1.
Time period and Frequency for collecting AE 
and SAE information...................................................50
7.4.1.2.
Method of Detecting AEs and SAEs ...........................51
7.4.1.3.
Follow-up of AEs and SAEs........................................51
7.4.1.4.
Cardiovascular and Death Events ..............................51
7.4.1.5.
AEs of Special Interest ...............................................52
7.4.1.6.
Regulatory Reporting Requirements for SAEs............52
7.4.2.
Pregnancy ...................................................................................53
7.4.3.
Physical Exams ...........................................................................53
7.4.4.
Vital Signs....................................................................................54
7.4.5.
Electrocardiogram (ECG).............................................................54
7.4.6.
Clinical Safety Laboratory Assessments ......................................54
7.4.7.
Estimated Glomerular Filtration Rate (eGFR) ..............................57
7.4.8.
Diabetic Dietary, Exercise, and Home Plasma Glucose 
Monitoring Advice ........................................................................57
7.4.9.
Hypoglycemic Events...................................................................57
7.5.
Tracking of Albiglutide Lyophilized DCC Pen Injector and Liquid 
Auto-injector Failures and User Errors........................................................58
7.6.
Pharmacokinetics .......................................................................................58
7.6.1.
Blood Sample Collection..............................................................58
7.6.2.
Sample Analysis ..........................................................................59
7.7.
Immunogenicity...........................................................................................59
7.8.
Genetics .....................................................................................................59
8.
DATA MANAGEMENT ...........................................................................................60
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................60
9.1.
Hypotheses.................................................................................................60
9.2.
Sample Size Considerations.......................................................................60
9.2.1.
Sample Size Assumptions ...........................................................60
9.2.2.
Sample Size Sensitivity................................................................61
9.2.3.
Sample Size Re-estimation or Adjustment...................................61
9.3.
Data Analysis Considerations .....................................................................62
9.3.1.
Analysis Populations....................................................................62
9.3.2.
Interim Analysis ...........................................................................62
9.4.
Key Elements of Analysis Plan ...................................................................62
9.4.1.
Primary Analyses.........................................................................62
9.4.2.
Secondary Analyses ....................................................................63
9.4.3.
Other Analyses ............................................................................64
9.4.4.
Supportive Analyses for Primary Endpoint...................................64
9.4.5.
Missing Data................................................................................65
9.4.5.1.
Impact of Missing Data on Primary Endpoint ..............65
9.4.5.2.
Extent of Missing Primary Analysis Data ....................65
9.4.5.3.
Reasons for Withdrawal .............................................65
9.4.5.4.
Handling of Missing Data............................................65


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10. STUDY GOVERNANCE CONSIDERATIONS........................................................67
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............67
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................67
10.3.
Quality Control (Study Monitoring) ..............................................................68
10.4.
Quality Assurance.......................................................................................68
10.5.
Study and Site Closure ...............................................................................68
10.6.
Records Retention......................................................................................69
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................70
10.8.
Review Committees....................................................................................70
11. REFERENCES.......................................................................................................71
12. APPENDICES........................................................................................................72
12.1.
Appendix 1: Abbreviations and Trademarks................................................72
12.2.
Appendix 2: GSK Modified List of Highly Effective Methods for 
Avoiding Pregnancy in Females of Reproductive Potential (FRP)...............75
12.3.
Appendix 3: Liver Safety Required Actions and Follow up
Assessments ..............................................................................................76
12.4.
Appendix 4: Genetic Research ...................................................................80
12.5.
Appendix 5: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events...............................................83
12.5.1.
Definition of Adverse Events........................................................83
12.5.2.
Definition of Serious Adverse Events...........................................84
12.5.3.
Definition of Cardiovascular Events .............................................85
12.5.4.
Recording of AEs and SAEs ........................................................86
12.5.5.
Evaluating AEs and SAEs............................................................86
12.5.6.
Reporting of SAEs to GSK...........................................................88
12.6.
Appendix 6: Collection of Pregnancy Information........................................89
12.7.
Appendix 7: Immunogenicity Testing Algorithm...........................................90
12.8.
Appendix 8: Country Specific Requirements...............................................92
12.9.
Appendix 9: Protocol Amendment Changes................................................93


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1.
PROTOCOL SYNOPSIS FOR STUDY 200952
Rationale
Albiglutide is a novel analogue of glucagon-like peptide-1 (GLP-1) with a sufficiently 
long half-life to permit once a week injection. Albiglutide has been developed for the 
treatment of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise, as 
monotherapy, or in combination with existing therapies and has been approved by the US 
Food and Drug Administration (FDA), the European Medicines Agency (EMA) and other 
regulatory agencies. 
Currently, lyophilized albiglutide and the diluent are provided in a dual chamber 
cartridge (DCC), single-dose pen injector, requiring reconstitution prior to use. A liquid 
formulation of albiglutide will enable the commercialization of a liquid product in a 
single dose, ready-to-use prefilled syringe in an auto-injector. Study 201287, a healthy 
volunteer bioequivalence study will be conducted as the first component of the 
comparability assessment and the proposed study, Study 200952, will be conducted as the 
final component. This study will compare the efficacy, safety, tolerability and 
pharmacodynamic (PD) response of the lyophilized DCC pen injector product to the 
liquid auto-injector product.  Specifically, potential for immunogenicity (e.g. incidences 
of anti-drug antibodies [ADA]) and injection site reactions (ISRs) will be evaluated.
Objective(s)/Endpoint(s)
Objectives
Endpoints
Primary

To evaluate the efficacy of albiglutide liquid 
product as measured by glycated 
hemoglobin (HbA1c) change from baseline 
at Week 26.

Change from baseline in HbA1c at Week 26
Secondary

To assess safety and tolerability of 
albiglutide specifically immunogenicity and 
ISRs.

Adverse events (AEs) and serious AEs 
(SAEs), physical examinations, clinical 
laboratory evaluations, vital signs, and 12-
lead electrocardiograms (ECGs).

Anti-albiglutide antibody production and 
rates of ISRs over time.

To evaluate the PD effect of albiglutide on 
fasting plasma glucose (FPG) change from 
baseline at Week 26.

Change from baseline in FPG at Week 26

To assess the PD effect of albiglutide over 
time

Change from baseline in HbA1c over time

Change from baseline in FPG over time

To evaluate trough PK concentrations of 
albiglutide following repeat dosing

Trough concentrations of albiglutide


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Overall Design

This is a phase III, randomized, double-blind, multicenter, parallel-group, repeat-
dose, study of 26 weeks duration to evaluate the efficacy, safety, tolerability and PD 
response of albiglutide liquid drug product relative to the commercial lyophilized 
drug product in subjects with T2DM failing to achieve optimal glycemic control on 
their current regimen of diet and exercise or stable dose of metformin.

At randomization, subjects will be stratified by age (<65 or ≥65 years of age), weight 
(<90 kg or ≥90 kg), and background antidiabetic therapy (diet and exercise or stable 
dose of metformin).
Treatment Arms and Duration

This study will comprise 3 study periods: screening (2 weeks), treatment (26 weeks) 
and for those subjects not entering the extension study a follow-up period (8 weeks).

Subjects will be randomized in a 1:1 ratio to either: 

Albiglutide active liquid auto-injector  + placebo lyophilized DCC pen injector; 
or,

Albiglutide active lyophilized DCC pen injector + placebo liquid auto-injector.

Study treatment will be administered once weekly by subcutaneous (s.c.) injection in 
the abdomen, thigh, or upper arm.

Subjects will receive 30 mg of albiglutide for 4 weeks and will then be up-titrated to 
50 mg albiglutide for the remaining 22 weeks of the study. 
Type and Number of Subjects

The study will recruit subjects with T2DM (>3 months since diagnosis) who are 
failing to achieve optimal glycemic control (HbA1c 7-10%) on their current regimen 
of diet and exercise or stable dose of metformin (maintained for approximately 8 
weeks prior to screening).

Approximately 300 subjects will be randomized. 
Analysis
Primary analyses:
HbA1c change from baseline at Week 26 will be analyzed using a mixed-effect model 
with repeated measures (MMRM) in the intent-to-treat (ITT) population.  MMRM will 
use all available data, including post-hyperglycemia rescue data, and will include data 
from subjects who discontinue treatment.  Imputation under the non-inferiority null 
hypothesis for missing data will be incorporated. Non-inferiority testing will be 
performed at a one-sided alpha of 0.025 and non-inferiority margin of 0.4.


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Secondary analyses:
The evaluation of the safety and tolerability as assessed by immunogenicity and ISRs of 
albiglutide liquid drug product and the lyophilized drug product will be provided by 
reporting the event rates, and the associated 95% CI. 
The overall general safety and tolerability of albiglutide liquid drug product versus 
lyophilized drug product will be evaluated in tabular and/or graphical format and 
summarized descriptively.
The secondary endpoint FPG change from baseline at Week 26 will be analyzed using 
MMRM without imputation. 
To assess the PD effect of albiglutide over time for the secondary endpoints change from
baseline in HbA1c and in FPG over time MMRM models will be used.
PK trough plasma concentration data will be summarized by treatment. 


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2.
INTRODUCTION
Albiglutide is a novel analogue of GLP-1 with a sufficiently long half-life to permit once 
a week injection. Albiglutide has been developed for the treatment of T2DM as an 
adjunct to diet and exercise, as monotherapy, or in combination with existing therapies. 
2.1.
Study Rationale
Currently, lyophilized albiglutide and the diluent are provided in a DCC, single-dose pen 
injector, requiring reconstitution prior to use. A liquid formulation of albiglutide will 
enable the commercialization of a liquid product in a single dose, ready-to-use prefilled 
syringe in an auto-injector.  To support the development of the liquid auto-injector 
product, Study 201287, a healthy volunteer bioequivalence study will be conducted as the 
first component of the comparability assessment and the proposed study, Study 200952, 
will be conducted as the final component of the overall comparability assessment.
Extensive release and characterization testing has been utilized in studies to establish the 
comparability between samples of the liquid product and commercial lyophilized 
product.  These studies were performed to evaluate the relevant differences in the quality 
attributes of the liquid and lyophilized products. However, non clinical studies are not 
suitable for predicting clinically relevant comparability of immunogenicity potential.    
The albiglutide lyophilized products has been evaluated in an international program of 
studies involving approximately 9000 subject-years of overall exposure to date (including 
over 4000 subject-years of exposure to albiglutide) and has been found to have a 
favorable benefit:risk profile, including a low immunogenicity profile.  In the clinical 
program with the lyophilized product, a low incidence (4.4%) of ADA was detected. 
Antibodies were non-neutralizing and mostly low titer and transient in nature.  None of 
the antibodies impacted the pharmacokinetic (PK), PD or efficacy of the drug.  There was 
a higher frequency of ISRs in antibody positive subjects, however most subjects with an 
ISR (including those ISRs classified as serious) were antibody negative.  There was no 
apparent relationship between antibody positive status and other AEs that could be 
attributed to albiglutide. 
This repeat-dose study in T2DM patients will determine if there are any clinically 
relevant differences between liquid drug product stored under recommended storage 
conditions to lyophilized drug product with respect to efficacy, safety, tolerability and PD 
response. Specifically, the immunogenicity potential (e.g., incidences of ADA) and ISRs 
will be evaluated as part of the overall safety assessment in this study.
2.2.
Brief Background
Diabetes affects an estimated 347 million people worldwide, T2DM accounting for more 
than 90% of cases [World Health Organization, 2013]. The primary manifestation of this 
disease is chronic hyperglycemia, resulting from resistance to insulin action at a cellular 
and molecular level and a relative inadequacy in the secretion of endogenous insulin 
[American Diabetes Association, 2014]. Chronic hyperglycemia has been firmly 
established as a key factor in the development of microvascular complications 


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(retinopathy, nephropathy, and neuropathy) and to a lesser extent, macrovascular 
complications. The rapidly increasing incidence and prevalence of T2DM is a major 
worldwide healthcare issue due to increased patient morbidity and mortality and the costs 
associated with the management of these complications.
The management of glycemia in individuals with T2DM consists of diet, exercise, and 
weight reduction together with oral anti-diabetic drugs, injectable agents such as GLP-1 
receptor agonists or insulin therapy, to achieve near normoglycemia as reflected by a 
target HbA1c level of 7%, where possible, without significant hypoglycemia or other 
adverse effects of treatment. Despite the large number of available therapeutic agents, a 
high proportion of subjects fail to achieve or maintain target HbA1c levels [Khunti, 2013] 
owing to the inexorable decline in endogenous insulin production characteristic of the 
disease, and limitations in existing treatments. New agents with complementary 
mechanisms (permitting combination use) or more favorable safety profiles are needed to 
help more subjects achieve glycemic targets.
Glucagon-like peptide-1 receptor agonists (e.g., exenatide, liraglutide, lixisenatide, 
dulaglutide) are therapeutic agents for the treatment of T2DM that stimulate insulin 
secretion in a glucose-dependent manner, suppress glucagon secretion with a low risk of 
hypoglycemia, delay gastric emptying, increase satiety, and are associated with modest
weight reduction. The GLP-1R agonists lower FPG levels and reduce postprandial 
glucose excursions. In addition, in preclinical models GLP-1R agonists stimulated 
transcription of genes important for glucose-dependent insulin secretion and promoted 
-cell neogenesis [Gautier, 2005]. 
Albiglutide is a novel analogue of GLP-1 generated through a genetic fusion of 2 
modified recombinant human GLP-1 molecules linked in tandem to recombinant human 
albumin. Albiglutide is licensed for the treatment of T2DM as an adjunct to diet and 
exercise, as monotherapy, or in combination with existing therapies (oral antidiabetic 
therapies or basal insulin). It has been granted marketing authorization by the EMA 
(March 2014), the FDA (April 2014), Switzerland (Sep 2014) and Health Canada (2015). 
Details of the clinical trial results can be found in the Investigator Brochure (IB).


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3.
OBJECTIVE(S) AND ENDPOINT(S)
Objectives
Endpoints
Primary

To evaluate the efficacy of albiglutide 
liquid product as measured by glycated 
hemoglobin (HbA1c) change from baseline 
at Week 26.

Change from baseline in HbA1c at 
Week26
Secondary

To assess safety and tolerability of 
albiglutide specifically immunogenicity 
and ISRs.

Adverse events (AEs) and serious AEs 
(SAEs), physical examinations, clinical 
laboratory evaluations, vital signs, and 
12-lead electrocardiograms (ECGs).

Anti-albiglutide antibody production and 
rates of ISRs over time.

To evaluate the PD effect of albiglutide on 
fasting plasma glucose (FPG) change 
from baseline at Week 26.

Change from baseline in FPG at Week 26

To assess the PD effect of albiglutide 
over time

Change from baseline in HbA1c over time

Change from baseline in FPG over time

To evaluate trough PK concentrations of 
albiglutide following repeat dosing

Trough concentrations of albiglutide
4.
STUDY DESIGN
4.1.
Overall Design

This is a phase III, randomized, double-blind, multicenter, parallel-group, repeat-
dose, study of 26 weeks duration to evaluate the efficacy, safety, tolerability and PD 
response of albiglutide liquid drug product relative to the commercial lyophilized 
drug product. 

The study will recruit subjects with T2DM who are failing to achieve optimal 
glycemic control on their current regimen of diet and exercise or stable dose of 
metformin. Subjects will continue on their current regimen for the duration of their 
participation in the study.

An overview of the study design is provided in Figure 1: 


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Figure 1
Study Schematic
Screening
Study Week
0
Albiglutide active lyophilized DCC pen injector1 + 
placebo liquid autoinjector (N= 150)
Albiglutide active liquid autoinjector1 + placebo 
lyophilized DCC pen injector   (N=150)
Treatment Period
−2
Primary Endpoint
T2DM
HbA1c 7% to 10%
34
26
Extension Study
or
Follow-up2
Baseline/
Randomization
DCC dual chamber glass cartridge
1.
At baseline/randomization, albiglutide will be started at 30 mg once weekly with uptitration to albiglutide 50 mg 
once weekly at Week 4. 
2.
Follow-up visit only for those subjects who discontinued investigational product (see Section 5.5), were withdrawn 
from the study, or who have completed the 26 week treatment period, but do not consent and/or are not eligible to 
participate in the 26 week extension study (Study 204682).

During the screening period, subjects will provide written informed consent and 
undergo procedures to determine eligibility for study participation. Screening will 
occur within 2 weeks of randomization. (Time and Events Table Section 7.1).

At randomization, subjects will be stratified by age (<65 or ≥65 years of age), weight 
(<90 kg or ≥90 kg), and background antidiabetic therapy (diet and exercise or stable 
dose of metformin).

Subjects who completed the 26 week treatment period, did not discontinue 
investigational product, and meet all eligibility criteria may consent to participate in 
Study 204682, a 26 week extension study. 
4.2.
Treatment Arms and Duration

This study will comprise 3 study periods (Figure 1): screening (2 weeks), treatment 
(26 weeks) and for those subjects not entering the extension study a follow-up period 
(8 weeks).

Subjects will be randomized in a 1:1 ratio to either: 

Albiglutide active liquid auto-injector  + placebo lyophilized DCC pen injector; 
or,

Albiglutide active lyophilized DCC pen injector + placebo liquid auto-injector.

Study treatment will be administered once weekly by s.c. injection in the abdomen, 
thigh, or upper arm.

Study personnel will administer study treatment at clinic visits.


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
Subjects will receive 30 mg of albiglutide for 4 weeks and will then be up-titrated to 
50 mg albiglutide for the remaining 22 weeks of the study. 

Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT 
permitted (see Section 4.4).  If a subject experiences tolerability issues with the 
higher 50mg dose then the subject may discontinue investigational product (at the 
discretion of the investigator) and will be followed for safety and efficacy.

During the study, any potential events of pancreatitis will be adjudicated by an 
independent pancreatitis adjudication committee (PAC) (Section 10.8).
4.3.
Type and Number of Subjects

The study will recruit subjects with T2DM (>3 months since diagnosis) who are 
failing to achieve optimal glycemic control (HbA1c 7-10%) on their current regimen 
of diet and exercise or stable dose of metformin (maintained for approximately 8 
weeks prior to screening).

Approximately 300 subjects will be randomized. 
4.4.
Design Justification
Based on a review of data from Phase IIb and Phase III studies with the lyophilized 
albiglutide product a primary endpoint of 26 weeks was selected. In Phase IIb and Phase 
III studies the peak incidences of immunogenicity and titers were observed between 16 to 
26 weeks of treatment.  Therefore, the selected 26 week treatment duration should 
appropriately capture the rate of immunogenicity with the albiglutide liquid drug product. 
The treatment duration of 26 weeks will also allow for appropriate evaluation of 
glycemic control as measured by HbA1c and FPG.
The current study is also applying the concept of design and objectives from the multiple-
dose phase of Study GLP114856 which demonstrated the clinical comparability of 
Process 2 and Process 3 albiglutide lyophilized products in subjects with T2DM by 
showing that there were no clinically significant differences between Process 2 and 
Process 3 albiglutide lyophilized products with regards to safety and PD effects (i.e., 
HbA1c, FPG) after 12 weeks of repeat dosing. To further strengthen the design, the 
current study is expanded by extending the repeat dosing period to 26 weeks and by 
adding the uptitration dosing scheme of 30 mg to 50 mg to allow for a comprehensive 
assessment of the efficacy, safety, tolerability and PD of the albiglutide liquid drug 
product and lyophilized drug product.  
Subjects will receive 30 mg of albiglutide for 4 weeks and will then be up-titrated to 
50 mg albiglutide for the remaining 22 weeks of the study. The intent of the dose titration 
scheme is to mimic real-world utilization of albiglutide as well as to maintain 
consistencies with what was done in the Phase III program.  In the Phase III program, 
most studies used dose uptitration based on pre-specified glycemic criteria or clinical 
response. Based on the experience from pivotal Phase III studies for registration, the 
number of subjects withdrawing due to AEs or intolerance to albiglutide is expected to be 
low.  


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4.5.
Dose Justification
Phase III studies confirmed the glycemic efficacy of both 30 mg and 50 mg doses of 
albiglutide lyophilized product, and both were generally well-tolerated. Although the 
30 mg dose was effective at controlling glycemia for at least 2 years in many subjects 
with T2DM, an increase in dose to 50 mg weekly offered additional benefit without 
significant safety issues (See IB for further details).
In this study subjects will receive 30 mg of either albiglutide liquid drug product or 
albiglutide lyophilized drug product once weekly for 4 weeks and will then be up-titrated 
to 50 mg albiglutide for the remaining 22 weeks of the study.
4.6.
Benefit:Risk Assessment
The following sections outline the risk assessment and mitigation strategy for this 
protocol which would apply to both the approved lyophilized drug product and the new 
liquid drug product in development.
Albiglutide lyophilized drug product has been evaluated in an international program of 
studies involving over 4000 subject-years of exposure to albiglutide. The program 
included 8 well-controlled Phase III studies ranging in duration from 32 weeks to 3 years, 
and using both 30 mg and 50 mg once weekly dosing.  This has permitted a thorough 
assessment of efficacy, safety, and tolerability in a population of subjects with T2DM 
that spanned newly diagnosed individuals treated with diet and exercise alone through to 
subjects on background oral monotherapy, oral dual therapy, oral triple therapy, and basal 
insulin.  
Summaries of findings from both clinical and non-clinical studies conducted with the 
albiglutide (GSK716155) lyophilized drug product can be found in the IB and in the 
product labeling for those countries where marketing authorization has been granted. 
This is the first clinical investigation of the albiglutide liquid drug product in subjects 
with T2DM. A detailed description of the characteristics of the liquid product in the auto-
injector device and results of nonclinical studies with this investigational drug product are 
presented in the IB Supplement. 
Summary characteristics of the liquid formulation and the lyophilized formulation are 
shown in Table 1.


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Table 1
Composition of Albiglutide (Liquid and Lyophilized for Injection, 30 
mg/DCC and 50 mg/DCC)
Component
Liquid Albiglutide
Commercial Lyophilized Albiglutide
30 mg dose
50 mg dose
30 mg dose
50 mg dose
Injector type
Pre-filled syringe with auto-
injector  
DCC in Pen injector 
Final formulation pH
5.9
7.0
Final albiglutide
concentration
50 mg/mL
60 mg/mL
100 mg/mL
Injection volume
0.6 mL
1.0 mL
0.5 mL
Stability data thus far suggest that the same product-related variants/impurity profiles are 
present in the liquid and commercial lyophilized products when stored at the 
recommended conditions.  Based on the current understanding of albiglutide degradation 
pathways and clinical outcomes from exposure to variants/impurities; similar PK, PD, 
and clinical comparability between the liquid product and the lyophilized product is 
expected. 
4.6.1.
Risk Assessment
Key identified and potential risks associated with administration of albiglutide 
formulations in this study and mitigation strategies included in the protocol are 
summarized in Table 2. At this stage, the risk profile and associated pharmacovigilance 
and mitigation strategies are considered generally applicable to both the approved 
lyophilized product and the investigational liquid auto-injector. No risks specific to the 
liquid product have been identified in non-clinical studies to date.  Mitigation strategies 
for this study have been incorporated for those risks (e.g. immunogenicity, ISRs) where a 
potential for differences between the formulations have been recognized.
Please also refer to the IB and any IB supplements as well as the complete Guidance for 
the Investigator and local approved product labeling.


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Table 2
Risk Assessment for Albiglutide (GSK716155)
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) (albiglutide [GSK716155])
Identified Risks
Pancreatitis
Acute pancreatitis has been reported in association with 
albiglutide and other GLP-1 receptor agonists in clinical 
trials and during postmarketing experience.
Albiglutide has not been studied in subjects with a history 
of pancreatitis to determine whether they are at increased 
risk for pancreatitis. 
Subjects with a history of acute or chronic pancreatitis are 
excluded from entering the study (See Section 5.2).
Subjects will be informed of the characteristic symptom of 
pancreatitis: persistent severe abdominal pain. If 
pancreatitis is suspected, albiglutide should be promptly 
discontinued and if pancreatitis is confirmed, study 
treatment will not be restarted (see Section 5.5).
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.
Gastrointestinal (GI) events.
Albiglutide has not been studied in subjects with severe GI 
disease, including severe gastroparesis. 
Use of albiglutide can be associated with GI side effects 
such as diarrhea, nausea, and vomiting.
Subjects with severe gastroparesis are excluded from 
entering the study (See Section 5.2).
Subjects with a history of significant GI surgery that in the 
opinion of the investigator is likely to significantly affect 
upper GI or pancreatic function are excluded from 
entering the study (See Section 5.2).
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Hypoglycemia.
Albiglutide’s mechanism of action is associated with a low 
intrinsic risk of significant hypoglycemia when used as 
monotherapy or in combination with agents such as 
metformin which also have low intrinsic risk for significant 
hypoglycemia. 
To reduce the risk of hypoglycemia when starting 
albiglutide all subjects are required to have HbA1c ≥7.0 at 
screening (see Section 5.1). 
Subjects are neither allowed to use insulin nor insulin 
secretagogues during the study except as part of 
hyperglycemia rescue (see Section 5.4)
Risk communication via guidance for investigators (see the 
albiglutide IB) and informed consent form for subjects.
Immunogenicity 
(e.g., including anti-drug antibodies, clinical sequelae of 
antidrug antibodies, severe hypersensitivity reactions, and 
other potential immune-related AEs).
Risk assessment of the albiglutide molecule predicted low 
immunogenic potential, which was substantiated for the 
commercial lyophilized DCC pen injector product in the 
registration program. Treatment-emergent anti-drug 
antibodies were detected in ~5% subjects over studies of 
up to 3 years duration and were generally transient, of low 
titer, and not neutralizing.
Subjects who tested positive for anti-albiglutide antibodies 
experienced a similar glycemic response (HbA1c and 
fasting plasma glucose) to those who did not test positive 
for antibodies. Other than injection site reactions (see 
below), the overall safety profile appeared similar among 
the subset of subjects who did and those who did not test 
positive for anti-albiglutide antibodies. 
Changes in the propensity of the liquid product to form 
aggregates could have an impact on anti-drug antibody 
characteristics or immune related AEs.  However, the 
likelihood of clinically important changes in anti-drug 
antibody characteristics or immune related AEs with the 
liquid albiglutide drug product compared to the lyophilized 
drug product is considered low based on the absence of 
substantive qualitative differences between formulations.
A pre-exposure baseline serum sample will be taken and 
tested for pre-existing ADAs.
The development of anti-albiglutide antibodies will be 
assessed as part of this study.
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for the subject.
Hypersensitivity Reactions
Systemic allergic/hypersensitivity reactions are of potential 
concern with any injected protein and were reported rarely 
in the Phase III program with lyophilized albiglutide. Data 
Subjects with a known allergy to albiglutide or any product 
components (including yeast and human albumin) are 


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
have not demonstrated an association of albiglutide with 
an increased incidence of anaphylaxis, angioedema, or 
urticaria. However, there was one non-serious 
hypersensitivity event (rash and itching associated with 
dyspnea upon rechallenge) that was consistent with a 
possible albiglutide-related systemic hypersensitivity 
reaction in a female subject who was anti-albiglutide 
antibody negative. See albiglutide IB.
excluded from the study (See Section 5.2).  
Subjects will be informed of the symptoms of severe 
hypersensitivity or allergy and be advised to seek medical 
assistance immediately. 
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.
Injection site reactions (ISRs)
Albiglutide injections may cause rash, erythema or itching 
and/or other reactions at the site of injection. 
In the Phase III program with the lyophilized drug product, 
most subjects with ISRs did not test positive for anti-
albiglutide antibodies. However, injection site reactions 
were reported more frequently among those who did test 
positive for anti-albiglutide antibodies (41% of the ADA 
positive subjects reported one or more injection site 
reactions) than among those who were consistently 
antibody negative (14% of the antidrug antibody negative 
subjects reported one or more injection site reactions).  
Overall, for albiglutide, injection site reactions have not 
been associated with clinically significant sequelae; 
although they can be a tolerability issue and were the most 
common reason for withdrawal of study medication for 
subjects (approximately 2.0%) in the albiglutide group.
Differences between formulation characteristics (e.g. lower 
pH and larger volume for the 50 mg dose of the liquid 
formulation) may impact the injection site reaction profile.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via guidance for investigators (see 
albiglutide IB)) and informed consent form for subjects.
The development of injection site reactions will be 
assessed as part of this study where the investigator or 
designee will administer both the albiglutide liquid drug 
product and the albiglutide lyophilized drug product.
Other adverse reactions
(e.g., pneumonia, atrial fibrillation/atrial flutter, and 
appendicitis) 
In the Phase III program in T2DM, other possible 
albiglutide related adverse reactions were identified. These 
events occurred at a cumulative incidence <3% in studies 
up to 3 years in duration. These events were reported 
more frequently with albiglutide than comparators. See 
albiglutide IB.
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) (albiglutide [GSK716155])
Potential Risks
Thyroid C-cell tumors
GLP-1 receptor agonists, including albiglutide increase 
serum calcitonin in rodents and other GLP-1 receptor 
agonists are associated with thyroid C-cell focal 
hyperplasia and C-cell tumors in rodents  It is unknown 
whether GLP-1 receptor agonists are associated with 
thyroid C-cell tumors in humans, including medullary 
thyroid cancer (MTC). 
Subjects with a personal or family history of MTC or 
subjects with Multiple Endocrine Neoplasia syndrome type 
2 (MEN-2) are excluded from the study (See Section 5.2).
Subjects with treatment emergent thyroid nodules should 
be referred to a specialist for evaluation in accordance with 
local treatment guidelines.  Routine monitoring of serum 
calcitonin is not recommended.  However, if serum 
calcitonin is found to be elevated the subject should be 
referred to a specialist for further evaluation. If MTC or 
other thyroid C-cell neoplasia is diagnosed, study 
treatment will be discontinued (see Section 5.5).
Other malignant neoplasms
Theoretical concerns have been raised regarding use of 
incretin based therapies and other malignancies such as 
pancreatic cancer [Egan, 2014] and malignancy when 
used in combination with insulin based on hypotheses of 
biological plausibility [European Public Assessment 
Report, 2014], and hematological malignancies [FDA
Summary Basis of Approval, 2014].
Relevant data on pancreatic cancer are summarized in the 
albiglutide IB.
Subjects with a history of cancer that has not been in full 
remission for at least 3 years before screening are 
excluded from the study (See Section 5.2). A history of 
squamous cell or basal cell carcinoma of the skin or 
treated cervical intra-epithelial neoplasia I or II is allowed.
Cardiovascular (CV) safety of antidiabetic therapy
T2DM is associated with an elevated risk of CV disease. 
Global regulatory agencies require new antidiabetic 
therapies to demonstrate that the new therapy is not 
associated with an unacceptable increase in CV risk. 
In the Phase III registration program, an independent 
Clinical Endpoint Committee prospectively adjudicated 
blinded CV events. The final CV meta-analysis showed no 
increased CV risk (MACE [major adverse cardiovascular 
event] + composed of CV death, myocardial infarction [MI], 
stroke, and hospitalization for unstable angina) with 
albiglutide versus all comparators (MACE+ hazard ratio = 
Relevant data on cardiovascular events are summarized in 
the albiglutide IB.
Subjects with clinically significant CV and/or 
cerebrovascular disease within 3 months before screening 
will be excluded from the study. Further details are 
provided in Section 5.2


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
1.00; 95% CI: 0.68, 1.49). See Section 5.4 of the IB.
Hepatotoxicity
Hepatotoxicity is an area of interest in drug development.  
Patients with T2DM are at increased risk for liver enzyme 
abnormalities and disease related liver conditions.  One 
subject treated with albiglutide in the Phase III clinical 
program developed probable drug induced liver injury with 
an asymptomatic elevation in alanine amino transferase 
(ALT) and total bilirubin although the cases had some 
atypical features and complicating factors . 
Routine liver safety laboratory evaluations will be 
conducted and specific withdrawal criteria for elevated liver 
function tests have been defined (See Section 5.5.4).


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) (albiglutide [GSK716155])
Additional Considerations
Subject population with severe renal impairment 
(estimated glomerular filtration rate (eGFR) 
<30 mL/min/1.73m2)
Experience in T2DM subjects with severe renal impairment 
is limited (in the Phase III programme a total of 19 subjects 
with eGFR <30 mL/min/1.73m2 received albiglutide). 
In a Phase III study of patients with varying degrees of 
renal impairment, in the albiglutide group, on-therapy GI 
AEs occurred with a higher incidence and higher event rate 
in subjects with moderate and severe renal impairment 
compared to those with mild renal impairment. GI events 
may lead to dehydration and worsen renal function. 
Subjects with an eGFR ≤30 mL/min/1.73 m2 (calculated 
using the Modification of Diet in Renal Disease (MDRD) 
formula) are excluded from the study (see Section 5.2).
Risk communication via guidance for investigators (see the 
albiglutide IB) and informed consent form for subjects.  
Drug interactions
Albiglutide causes a delay in gastric emptying, and thereby 
has the potential to impact the absorption of concomitantly 
administered oral medications.
During the development program, drug interactions 
studies were conducted with digoxin, warfarin, oral 
contraceptives, and simvastatin which demonstrated no 
clinically relevant PK or PD effects. 
Investigators will be advised to take the effect of albiglutide 
on gastric emptying into account when prescribing 
concomitant medication.
Fetal & neonatal developmental toxicity
Studies in animals have shown reproductive toxicity. The 
potential risk for humans is unknown.  Albiglutide 
administration during the major period of organogenesis in 
female mice resulted in embryofetal lethality, and 
bent/wavy ribs in the fetus at 50 mg/kg/day.  Offspring of 
mice dosed with 50 mg/kg/day during organogenesis had 
reduced pre-weaning body weight (which recovered after 
weaning), dehydration and coldness, and a delay in 
balanopreputial separation.
Given that albiglutide is an albumin-based protein 
therapeutic, it is likely to be transferred to breast milk. 
Decreased body weight in offspring was observed in mice 
treated with albiglutide during gestation and lactation.
Subjects who are breastfeeding, pregnant or planning a 
pregnancy during the course of the study are excluded. 
Additionally, all females of child-bearing potential must be 
taking adequate contraception during the study and have a 
negative pregnancy test prior to entry.  See Section 5.1 for 
further details.
Risk communication via guidance for investigators (see IB) 
and informed consent form for subjects.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Accelerated sexual maturation in juveniles
Long-acting GLP-1R agonists have the potential to 
accelerate sexual maturation in monkeys based on 
absolute testes weight and similar trends in prostate, 
seminal vesicle, epididymides weights and histological 
assessment of maturity.
Subjects under 18 years of age are excluded (see Section 
5.1).
Study Procedures
Albiglutide matching placebo injections
Albiglutide placebo injections using the lyophilized DCC 
pen injector were associated with a clinically relevant rate 
of injection site reactions in the Phase III studies.
There is no experience with placebo injections using the 
liquid auto-injector, including volume and pH differences 
from the lyophilized product placebo.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via informed consent form for 
subjects.


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4.6.2.
Benefit Assessment
In subjects with T2DM treatment with albiglutide lyophilized drug product resulted in 
clinically relevant lowering of HbA1c at both the 30 mg and 50 mg doses when given as 
monotherapy and in combination with metformin, sulfonylureas (SUs), thiazolidinedione 
or basal insulin. The durability of the effect on glycemic control was shown over a study 
period of up to 3 years. Consistent with its mechanism of action, albiglutide was not 
associated with clinically relevant hypoglycemia except when used in combination with 
an SU or insulin, and incidence rates with the combination were less than those reported 
with SUs or insulin alone. Body weight decreased slightly or remained stable during 
treatment, which is of benefit considering that continuous weight gain is a clinical 
problem in this patient group. Maintaining body weight while decreasing HbA1c is 
therefore considered a beneficial effect of importance.
There are no clinical data available for the use of the albiglutide liquid drug product in 
humans. Based on the understanding of albiglutide degradation pathways and clinical 
outcomes from exposure to variants/impurities clinical comparability between the liquid 
drug product and lyophilized drug products is expected.
4.6.3.
Overall Benefit: Risk Conclusion
Taking into account the measures taken to minimize risk to subjects participating in this 
study, the known and potential risks identified with albiglutide are justified by the 
benefits demonstrated in subjects with T2DM.


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5.
SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, AEs, and other 
pertinent information on the GSK investigational product or other study treatment that 
may impact subject eligibility is provided in the IB and in the product labeling for those 
countries where marketing authorization for the albiglutide lyophilized DCC pen injector 
has been granted. 
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
5.1.
Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
[1] AGE
1.
Aged 18 to 80 years of age inclusive, at the time of signing the informed consent.
[2] TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 
2.
Historical diagnosis of T2DM (at least 3 months), experiencing inadequate glycemic 
control on current regimen of diet and exercise or on a stable dose of metformin of at 
least 1500 mg or the documented maximal tolerated dose if less than 1500 mg 
metformin (monotherapy), maintained for approximately 8 weeks prior to screening
3.
HbA1c ≥7.0% and ≤10%. If the first screening HbA1c does not meet the eligibility 
criterion, the HbA1c value may be checked up to 2 times during screening, and if the 
average of these determinations meets the criterion, the subject can be randomly 
assigned to treatment.
4.
Hemoglobin ≥11 g/dL (≥110 g/L) for males and ≥10 g/dL (≥100 g/L) for females.
[3] WEIGHT
5.
Body mass index 40 kg/m2.
[4] SEX
6.
Male or female
7.
Female subject is eligible to participate if she is not pregnant (as confirmed by a 
negative serum human chorionic gonadotrophin (hCG) test for females of 
reproductive potential only), not breastfeeding, and at least one of the following 


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conditions applies:
a) Reproductive potential and agrees to follow one of the options listed in the GSK 
Modified List of Highly Effective Methods for Avoiding Pregnancy in Females 
of Reproductive Potential (FRP) (eg., combined oral contraceptive pill; see 
Appendix 2) from 30 days prior to the first dose of study medication and until 
after the last dose of study medication and completion of the follow-up visit.

This does not apply to FRP with same sex partners, when this is their preferred
and usual lifestyle or for subjects who are and will continue to be abstinent. 
Other situations in which contraception in FRP may not need to be mandated 
should be discussed with the Medical Monitor.
b) Non-reproductive potential defined as either:

Pre-menopausal with one of the following: (i) documented tubal ligation; (ii) 
documented hysteroscopic tubal occlusion procedure with follow-up 
confirmation of bilateral tubal occlusion; (iii) hysterectomy; or (iv) documented 
bilateral oophorectomy, or; 

Postmenopausal defined as 12 months of spontaneous amenorrhea and age 
appropriate (i.e., >50 years). In questionable cases, a blood sample with 
simultaneous follicle stimulating hormone (FSH) >40 mIU/mL and estradiol 
<40 pg/mL (<140 pmol/L) is confirmatory, depending on local laboratory 
ranges.  Females on hormone replacement therapy (HRT) and whose 
menopausal status is in doubt will be required to use one of the highly effective 
contraception methods if they wish to continue their HRT during the study.  
Otherwise, they must discontinue HRT to allow confirmation of post-
menopausal status prior to study enrolment.
[5] INFORMED CONSENT
8.
Able and willing to provide informed consent.
5.2.
Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
[1]  CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER 
FUNCTION AND QTc INTERVAL) 
1.
Type 1 diabetes mellitus
2.
History of cancer that has not been in full remission for at least 3 years before 
screening. (A history of squamous cell or basal cell carcinoma of the skin or treated 
cervical intra-epithelial neoplasia I or II is allowed).
3.
Personal or family history of medullary thyroid carcinoma or multiple endocrine 
neoplasia type 2. 
4.
History of acute or chronic pancreatitis.
5.
Abnormal (i.e., outside the normal reference range) thyroid stimulating hormone 


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(TSH) at screening.
6.
Severe gastroparesis, i.e., requiring regular therapy within 6 months before 
screening.
7.
History of significant GI surgery that in the opinion of the investigator is likely to 
significantly affect upper GI or pancreatic function (e.g., gastric bypass and banding, 
antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or 
surgeries thought to significantly affect upper GI function).
8.
History of severe hypoglycemia unawareness (i.e., the absence of autonomic warning 
symptoms before the development of neuroglycopenic symptoms such as blurred 
vision, difficulty speaking, feeling faint, difficulty thinking, and confusion)..
9.
Diabetic complications (e.g., active proliferative retinopathy or severe diabetic 
neuropathy) or any other clinically significant abnormality (including a psychiatric 
disorder) that, in the opinion of the investigator, may pose additional risk in 
administering the investigational product.
10. Clinically significant CV and/or cerebrovascular disease within 3 months before 
screening including, but not limited to, the following: 

Stroke or transient ischemic attack.

Acute coronary syndrome (MI or unstable angina not responsive to 
nitroglycerin).

Cardiac surgery or percutaneous coronary procedure.

Current or history of heart failure (New York Heart Association class III or IV).
11. QTcF > 470 msec, where QTcF is the QT interval corrected for heart rate according 
to Fridericia’s formula.
12. ALT >2.5xULN or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable 
if bilirubin is fractionated and direct bilirubin <35%). 
13. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or 
asymptomatic gallstones or otherwise stable chronic liver disease per investigator 
assessment). 
NOTES: 

Stable chronic liver disease should generally be defined by the absence of 
ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or 
gastric varices, or persistent jaundice, or cirrhosis.

Chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen 
(HBsAg) or positive hepatitis C antibody test result at screening or within 3 
months prior to first dose of study treatment) are acceptable if subject otherwise 
meets entry criteria.
14. eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula) at screening.
Note: The use of metformin in subjects with varying degrees of renal function   
should be in accordance with the metformin product label.


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15. Hemoglobinopathy that may affect proper interpretation of HbA1c.
16. Medical or psychiatric disorders that would preclude effective participation in study.
[2] CONCOMITANT MEDICATIONS (see Section 6.10)
17. Use of oral or systemically injected glucocorticoids within the 3 months before 
randomization or high likelihood of a requirement for prolonged treatment (>1 week) 
in the 6 months following randomization. However, short courses of oral steroids 
(single dose or multiple doses for up to 7 days) may be permitted provided these 
cases are discussed with the medical monitor. Inhaled, intra-articular, epidural, and 
topical corticosteroids are allowed.
18. Use of GLP 1 receptor agonists at any time. Use of dipeptidyl peptidase-IV 
inhibitors within the 3 months before randomization. Use of any other antidiabetic 
medications with the exception of metformin within 3 weeks before randomization.
[3] RELEVANT HABITS
19. History of alcohol or substance abuse within one year before screening.
[4] CONTRAINDICATIONS 
20. Known allergy to albiglutide or any product components (including yeast and human 
albumin), any other GLP-1 analogue, or other study medication’s excipients OR 
other contraindications (per the prescribing information) for the use of potential 
study medications.
[5] DIAGNOSTIC ASSESSMENTS AND OTHER CRITERIA
21. Positive urine alcohol/drug screen result at Screening, unless the subject is taking a 
medically approved medication for which a positive drug screen simply verifies the 
use of this medication 
22. A positive test for human immunodeficiency virus (HIV) antibody.
23. The subject has participated in a clinical trial and has received an investigational 
product within the following time period prior to the first dosing day in the current 
study: 30 days, 5 half-lives or twice the duration of the biological effect of the 
investigational product (whichever is longer).
24. Fasting triglyceride level >750 mg/dL at screening.


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5.3.
Screening/Baseline/Run-in Failures
Screen failures are defined as subjects who consent to participate in the clinical trial but 
are never subsequently randomized. In order to ensure transparent reporting of screen 
failure subjects, meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, and respond to queries from regulatory authorities, a minimal 
set of screen failure information is required including demography, screen failure details, 
eligibility criteria, and any SAEs.

Re-screening of subjects who did not meet the eligibility criteria for HbA1c (≥7.0% 
and ≤10%) is permitted. If the first screening HbA1c does not meet the eligibility 
criterion, the HbA1c value may be checked two further times during the screening 
period, and if the average of these determinations meets the entry criterion, the 
subject can be randomized.
5.4.
Hyperglycemia Rescue
During the study of diabetics, there is always the possibility of hyperglycemia, which 
might impact subject safety. After randomization, subjects who experience persistent 
hyperglycemia will qualify to undergo hyperglycemia rescue. Investigators must adhere 
to the labeling of the US FDA-approved prescribing information or to the local labeling 
of the respective country for all rescue medications. The conditions for hyperglycemia 
rescue are defined in Table 3.
Table 3
Conditions for Hyperglycemia Rescue
Time Interval on Treatment
Hyperglycemia Rescue
≥Day 1 and <Week 2
No rescue
≥Week 2 and <Week 4
FPG ≥280 mg/dL1 
≥Week 4 and <Week 12
FPG ≥250 mg/dL1
≥Week 12 and <Week 26
HbA1c ≥8.5% and 0.5% reduction from Baseline
1.
Confirmed by a second sample drawn within 7 days analyzed by the central laboratory
Subjects can be rescued at any time on or after Week 2. Subjects who qualify should 
return to the study center at the next scheduled weekly visit for rescue.  The efficacy 
assessments should be obtained if these assessments are not included as part of the 
regular scheduled visit.  As determined by the investigator, rescued subjects may be seen 
more frequently during unscheduled visits until their diabetes has stabilized. Subjects will 
continue in the study after rescue and will continue with their blinded study treatment 
until the study is completed. It is critical that subjects continue in the study after rescue in 
order to have complete and unbiased follow-up of long-term safety and efficacy 
assessments. 
The rescue criteria above should apply in the majority of circumstances; however, in the 
event a subject experiences significant evidence of hyperglycemia (e.g., symptoms of 
polyuria and polydipsia and laboratory evidence of hyperglycemia), the investigator may, 
based upon his or her judgment, rescue the subject with appropriate therapy at any time 
following randomization. Such subjects may either have rescue medication added to the 


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existing randomly assigned study medication or, if in the judgment of the investigator (or 
the product labeling for rescue medications) this is not appropriate, the subject will be 
discontinued from randomly assigned study medication and appropriate rescue therapy 
initiated. Such subjects will continue to be followed in the study for their safety 
information; however, they will not receive further randomly assigned study medication. 
Rather they will be prescribed alternative therapy in order to optimize their diabetes 
control.
The preferred postrescue add-on treatment is insulin. Other medications may be added at 
the investigator’s discretion. The addition of other GLP-1 analogues (exenatide or 
liraglutide) is prohibited as the safety of dosing with multiple GLP-1 analogues is 
unknown. The use of dipeptidyl peptidase-IV inhibitors is prohibited. The addition of a 
thiazolidinedione (rosiglitazone or pioglitazone) is discouraged.
5.5.
Withdrawal/Stopping Criteria
Every effort should be made to keep subjects in the study. The reason for a subject 
discontinuing investigational product or withdrawing from the study will be recorded in 
the subject’s electronic case report form (eCRF). 
5.5.1.
Permanent Discontinuation of Investigational Product
A subject may permanently discontinue investigational product at any time at his/her own 
request, or at the discretion of the investigator for safety or compliance reasons.  A 
subject must permanently discontinue investigational product for the pre-specified 
reasons below. 

Any AE, which, in the opinion of the investigator precludes effective participation of 
the subject or poses a safety concern

The following AEs will require discontinuation from investigational product:

Confirmed pancreatitis, acute or chronic. 

Pancreatic cancer.

Confirmed MTC or other thyroid C-cell neoplasia.  

Liver chemistry abnormalities exceeding the threshold criteria outlined in 
Section 5.5.4

QTc abnormalities exceeding the threshold criteria outlined in Section 5.5.5.

Severe allergic/hypersensitivity reactions that are considered by the 
investigator to be attributable to investigational product or without a likely 
alternative aetiology.

eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula).

Subject becomes pregnant or intends to become pregnant during the study.

Need for chronic use of a prohibited concomitant medication (Section 6.10.2)


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
Major protocol deviation (the investigator should discuss the protocol deviation with 
the medical monitor before withdrawing study medication)

Subject decision (reason to be documented in the eCRF, if specified by the subject)

Investigator discretion 

Study closed/terminated or investigator site closed (where subject transfer to another 
site is not possible)
In all cases, the reasons for investigational product discontinuation and the date of the last 
dose will be recorded in the subject’s electronic case report form (eCRF) and the subject 
will continue in the study as described in 5.5.1
5.5.1.1.
Procedures for Subject Follow-up Following Discontinuation of 
Investigational Product
Subjects will be educated on the importance of remaining in the study and attending all
scheduled study visits. 
Subjects who permanently discontinue investigational product will be expected to attend 
clinic visits every 4 weeks through the End of Treatment visit, according to the study visit 
schedule, unless consent is actively withdrawn. Complete details are provided in the 
Time and Events Table (Section 7.1).
If a subject is unable or unwilling to continue attending clinic visits in person, other 
subject follow-up options to collect subject information as detailed in the informed 
consent (e.g., telephone calls, letters, review of subjects medical records) should be 
pursued.
5.5.2.
Subjects Who Fail to Attend Clinic Visits
The following actions must be taken in relation to a subject who fails to attend the clinic 
for a required study visit:

The site must attempt to contact the subject and re-schedule the missed visit as soon 
as possible. 

The site must counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 

In cases where the subject is deemed ‘lost to follow up’, the investigator or designee 
must make every effort to regain contact with the subject (where possible, 3 telephone 
calls and if necessary a certified letter to the subject’s last known mailing address or 
local equivalent methods). These contact attempts should be documented in the 
subject’s medical record. 

Should the subject continue to be unreachable, only then will he/she be considered to 
have withdrawn from the study with a primary reason of “Lost to Follow-up”. 


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5.5.3.
Withdrawal from Study
Every effort should be made to keep subjects in the study. For subjects that choose to 
withdraw consent or are lost to follow up, the reason for not completing the study will be 
recorded in the subject’s eCRF. If a subject withdraws from the study, he/she may request 
destruction of any samples taken, and the investigator must document this in the site 
study records. 
Subjects who are withdrawn or discontinue active participation in the study will no 
longer receive the randomized study treatment. Immediately upon discontinuation from 
active participation in this study, these subjects should complete the assessments as per 
the end of treatment clinic visit and return for the post-treatment follow-up clinic visit 8 
weeks later (Section 7.1). If a subject is unable or unwilling to return for the follow-up 
assessments, every effort will be made to follow-up with the subject.
Withdrawn subjects will not be replaced. 
5.5.4.
Liver Chemistry Stopping Criteria
Phase III-IV Liver Chemistry Stopping and Increased Monitoring Algorithm
Continue Study Treatment 
Discontinue Study Treatment 
Plus 
Bilirubin≥2x
ULN (>35% 
direct) or plus
INR>1.5, if 
measured*
Possible  
Hy’s Law
ALT≥3xULN
ALT
≥8xULN
Plus
Symptoms of 
liver injury
or 
hypersensitivity
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
*INR value not applicable to subjects on anticoagulants 
ALT 
≥3xULN 
but 
<8xULN
Yes
Must refer to Liver Safety Required Actions and Follow up Assessments section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*


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Liver Safety Required Actions and Follow up Assessments Section can be found in 
Appendix 3.
Phase III-IV Liver Chemistry Increased Monitoring Algorithm with Continued 
Therapy for ALT 3xULN but <8xULN
Continue Study Treatment   and   Monitor Liver Chemistry
Discontinue Study Treatment 
ALT≥5xULN 
but <8xULN
+ bili <2xULN +
no symptoms
No
Must refer to Liver Safety Required Actions and Follow up Assessments section in the Appendix
Yes
ALT ≥3xULN 
but <5xULN
+ bili <2xULN  +
no symptoms
Able to 
monitor  
weekly 
for  ≥2 
weeks
Persists for 
≥2 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
No
No
Able to 
monitor  
weekly 
for  ≥4 
weeks
Persists for 
≥4 weeks  
or other 
stopping 
criteria  
met
No
Yes
Yes
Yes
Yes
ALT ≥5xULN 
ALT <5xULN 
Yes
Yes
*INR value not applicable to subjects on anticoagulants 
Must refer to Liver Safety Required Actions and Follow up Assessments section in the Appendix
Report as an SAE if possible Hy’s Law case: ALT≥3xULN and  Bilirubin≥2xULN (>35% direct)  or 
INR>1.5, if measured*
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Appendix 3.
5.5.4.1.
Study Treatment Restart or Rechallenge
Study treatment restart or rechallenge after liver chemistry stopping criteria are met by 
any subject participating in this study is not allowed.
5.5.5.
QTc Stopping Criteria

The QT interval corrected for heart rate according to Fridericia’s formula (QTcF) 
must be used for each individual subject to determine eligibility for and 
discontinuation from the study.  

The QTcF should be based on a single electrocardiogram (ECGs) obtained over a 
brief (e.g., 5-10 minute) recording period.  

A subject who meets the following criteria will discontinue investigational product:

QTcF >500 msec (or 530 msec for subjects with bundle-branch block or 
pacemaker)


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5.6.
Subject and Study Completion
A completed subject is one who has completed the 26 week treatment phase of the study. 
The end of the study is defined as the last subject’s last visit.
6.
STUDY TREATMENT
6.1.
Investigational Product and Other Study Treatment
The term ‘study treatment’ is used throughout the protocol to describe any combination 
of products received by the subject as per the protocol design. Study treatment may 
therefore refer to the individual study treatments or the combination of those study 
treatments.


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Study Treatment
Product name:
Lyophilized albiglutide DCC 
pen injector
Lyophilized albiglutide DCC 
pen injector matching placebo
Albiglutide liquid auto-injector 
Albiglutide liquid auto-injector 
matching placebo
Dosage 
form/Delivery 
system:
Lyophilized albiglutide is 
provided as a fixed-dose, fully 
disposable pen injector 
system for delivery of the 
study treatment from a 
prefilled dual chamber glass 
cartridge (DCC) that is an 
integral part of the injector 
pen. It is designed for manual 
reconstitution of the dose,
priming and insertion of the 
pen needle (29G), and 
manual injection.
The DCC contains lyophilized 
albiglutide (30mg or 50mg). 
When the injector pen product 
is reconstituted a neutral, 
isotonic solution is produced. 
The pen delivers albiglutide in 
an injection volume of 0.5 mL.
Lyophilized albiglutide 
matching placebo is provided 
as a fixed-dose, fully 
disposable pen injector 
system for delivery of the 
study treatment from a 
prefilled DCC that is an 
integral part of the injector 
pen. It is designed for manual 
reconstitution of the dose, 
priming and insertion of the 
pen needle (29G), and 
manual injection.
The DCC contains matching 
placebo. When the injector 
pen product is reconstituted a 
neutral, isotonic placebo 
solution is produced. The pen 
delivers the placebo in an 
injection volume of 0.5 mL.
Albiglutide liquid is provided 
as a fixed-dose, disposable 
auto-injector containing 
albiglutide liquid (30 mg or 
50 mg) in a prefilled glass 
syringe with staked 29G thin-
wall needle and needle shield.  
It is intended for single use. 
The cap remover is removed 
and the cover sleeve of the 
auto-injector is pressed 
against the skin, which results 
in automatic s.c. injection of 
the albiglutide liquid.
Albiglutide liquid (30mg or 
50mg) has a pH of 5.9.
The auto-injector delivers the 
study treatment in an injection 
volume of 0.6 mL for the 
30 mg dose and 1.0 mL for 
the 50 mg dose.
Liquid albiglutide matching 
placebo is provided as a 
fixed-dose, disposable auto-
injector containing placebo 
liquid in a prefilled glass 
syringe with staked 29G thin-
wall needle and needle shield.  
It is intended for single use. 
The cap remover is removed 
and the cover sleeve of the 
auto-injector is pressed 
against the skin, which results 
in automatic s.c. injection of 
the placebo liquid.
The placebo liquid has a pH 
of 5.9.
The auto-injector delivers the 
placebo in an injection volume 
of 0.6 mL for the 30 mg 
placebo dose and 1.0 mL for 
the 50 mg placebo dose.


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Study Treatment
Unit dose 
strength(s)
/Dosage level(s):
30mg or 50mg albiglutide
Matching placebo
30mg or 50mg albiglutide
Matching placebo
Route of 
Administration
Subcutaneous injection in the 
abdomen, thigh or upper arm 
region.
Rotation of injection sites is 
recommended. 
Subcutaneous injection in the 
abdomen, thigh or upper arm 
region.
Rotation of injection sites is 
recommended. 
Subcutaneous injection in the 
abdomen, thigh or upper arm 
region.
Rotation of injection sites is 
recommended. 
Subcutaneous injection in the 
abdomen, thigh or upper arm 
region.
Rotation of injection sites is 
recommended. 
Dosing 
instructions:
Administered as a single s.c. 
injection once a week on the 
same day each week.
Administered by study 
personnel at the weekly clinic 
visit.
Administered at any time of 
day without regard to meals.
Administered as a single s.c. 
injection once a week on the 
same day each week.
Administered by study 
personnel at the weekly clinic 
visit.
Administered at any time of 
day without regard to meals
Administered as a single s.c. 
injection once a week on the 
same day each week.
Administered by study 
personnel at the weekly clinic 
visit.
Administered at any time of 
day without regard to meals
Administered as a single s.c. 
injection once a week on the 
same day each week.
Administered by study 
personnel at the weekly clinic 
visit.
Administered at any time of 
day without regard to meals


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6.2.
Treatment Assignment
Randomized treatment assignment will be done via the Interactive Voice Response 
System (IVRS), and randomization will be implemented based on a sequestered fixed 
randomization schedule. Study centre personnel will call the IVRS to execute each 
randomization once a subject has met all prerequisites for randomization and has 
completed all scheduled screening assessments.
Subjects will be assigned to study treatment in accordance with the randomization 
schedule. Eligible subjects will be stratified by age (<65 or ≥65 years of age), weight 
(<90 kg or ≥90 kg), and background antidiabetic therapy (diet and exercise or stable dose 
of metformin).
Subjects will be randomized in a 1:1 ratio to either: 

Albiglutide active liquid auto-injector  + placebo lyophilized DCC pen injector; 
or,

Albiglutide active lyophilized DCC pen injector + placebo liquid auto-injector.
Blinded study centre personnel will receive a randomization notification indicating only 
the unique subject identifier and the date and time of randomization. Each subject number 
will be a unique identifier. Once a subject number has been assigned, the number will not 
be reused even if the subject withdraws before receiving any study treatment. 
6.3.
Planned Dose Adjustments
Subjects will receive 30 mg of either albiglutide liquid drug product or albiglutide 
lyophilized drug product during Weeks 1-4 and will then be up-titrated to 50 mg 
albiglutide for the remaining 22 weeks of the study (Weeks 5-26).  
Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT permitted.  If 
a subject experiences tolerability issues with the higher 50mg dose then the subject may 
discontinue investigational product (at the discretion of the investigator) and will be 
followed for safety and efficacy.
The use of metformin in subjects with varying degrees of renal function should be in 
accordance with the metformin product label. It is encouraged that a stable metformin 
dose is maintained during the study. However the metformin dose may be downtitrated 
based on clinical need at the discretion of the investigator. Up-titration of metformin is 
permitted for subjects who require hyperglycemic rescue and metformin is selected as the 
rescue medication.
6.4.
Blinding
This is a double-blind study; neither the subject nor the study physician will know which 
of the treatments (albiglutide liquid auto-injector or matching placebo and lyophilized
albiglutide DCC pen injector or matching placebo) the subject is receiving. The following 
will apply. 


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
The investigator or treating physician may unblind a subject’s treatment assignment 
only in the case of an emergency OR in the event of a serious medical condition 
when knowledge of the study treatment is essential for the appropriate clinical 
management or welfare of the subject as judged by the investigator. 

Investigators have direct access to the subject’s individual study treatment. 

It is preferred (but not required) that the investigator first contacts the Medical 
Monitor or appropriate GSK study personnel to discuss options before unblinding 
the subject’s treatment assignment. 

If GSK personnel are not contacted before the unblinding, the investigator must 
notify GSK as soon as possible after unblinding, but without revealing the treatment 
assignment of the unblinded subject, unless that information is important for the 
safety of subjects currently in the study. 

The date and reason for the unblinding must be fully documented in the eCRF 

If the subject’s treatment code is unblinded by the investigator or treating physician
the subject will continue to receive treatment unless they meet one of the 
investigational product discontinuation or study withdrawal criteria outlined in 
Section 5.5. 

GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
treatment assignment for any subject with an SAE. If the SAE requires that an 
expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
report, identifying the subject’s treatment assignment, may be sent to investigators in 
accordance with local regulations and/or GSK policy.
6.5.
Packaging and Labeling
The contents of the label will be in accordance with all applicable regulatory 
requirements.
6.6.
Preparation/Handling/Storage/Accountability
No special preparation of study treatment is required other than that described in Section 
6.1.
Only subjects enrolled in the study may receive study treatment and only authorized site 
staff may supply and administer study treatment.  All study treatments must be stored in a 
secure environmentally controlled and monitored (manual or automated) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(i.e. receipt, reconciliation and final disposition records). 
Further guidance and information for final disposition of unused study treatment are 
provided in the Study Reference Manual (SRM). 


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Under normal conditions of handling and administration, study treatment is not expected 
to pose significant safety risks to site staff.  Take adequate precautions to avoid direct eye 
or skin contact and the generation of aerosols or mists. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor and/or GSK study contact.
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from GSK.
6.7.
Compliance with Study Treatment Administration
The investigator or designee will administer study treatment to the subject in the clinic at 
the time points specified in the Time and Events Table (Section 7.1). The date and time 
of each dose administered in the clinic will be recorded in the source documents. The 
dose of study treatment and study subject identification will be confirmed at the time of 
dosing by a member of the study site staff other than the person administering the study 
treatment.
6.8.
Treatment of Study Treatment Overdose
No data are available with regard to albiglutide overdose in humans. The highest 
recommended dose of albiglutide is 50 mg once weekly.
During clinical studies of subjects with T2DM, the highest dose of albiglutide 
administered was 100 mg subcutaneously every 4 weeks for 12 weeks. This dose was 
associated with an increased frequency of nausea, vomiting, and headache. 
There is no specific antidote for overdose with albiglutide. In the event of a suspected 
overdose, the appropriate supportive clinical care should be instituted, as dictated by the 
subject’s clinical status. Anticipated symptoms of an overdose may be severe nausea, 
vomiting or headache.  A prolonged period of observation and treatment for these 
symptoms may be necessary, taking into account the half-life of albiglutide (5 days).
6.9.
Treatment after the End of the Study
Following completion of the Week 26 visit, eligible subjects who gave consent to 
participate in the extension study (Study 204682) will be treated as detailed in the 
extension study protocol. Those subjects who did not give consent to participate in the 26 
week extension study will return to the study centre in 8 weeks for the post-treatment 
follow-up visit (Week 34 visit). 
Investigational product will not be provided to subjects by GSK after the end of the 
study.
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the subject’s medical condition, whether or not GSK is providing specific 
post-study treatment.


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The half-life of albiglutide is approximately 5 days, and significant therapeutic 
concentrations can persist for 3 to 4 weeks after discontinuation.  The choice of other 
medicinal products and dose selection should be considered accordingly, as adverse 
reactions may continue and efficacy may, at least partly, persist until albiglutide levels 
decline.
6.10.
Concomitant Medications and Non-Drug Therapies
All medications taken at any time from screening to the follow-up visit will be recorded 
in the eCRF. The minimum requirement is that drug name and the dates of administration 
are to be recorded.
6.10.1.
Permitted Medications and Non-Drug Therapies
Unless specified as a prohibited medication in Section 6.10.2, all concomitant 
medications should be considered permitted provided they are not contraindicated  in the 
albiglutide Prescribing Information or for the individual subject concerned. Although 
stable doses of all concomitant medications are preferable, changes in medications during 
the study to appropriately treat clinical conditions that might arise are allowed. 
Like other members of the class, albiglutide causes a delay in gastric emptying, and 
thereby has the potential to impact the absorption of concomitantly administered oral 
medications.  This should be taken into account by investigators when prescribing 
concomitant medication.
Investigators must adhere to the local labeling of the respective country (e.g., the 
Summary of Product Characteristics (SmPC) in relevant European countries or the FDA-
approved prescribing information) for all permitted medications.
6.10.2.
Prohibited Medications and Non-Drug Therapies
Subjects must not use any of the following medications:

Dipeptidyl peptidase-IV inhibitors and GLP-1R agonists (except albiglutide liquid  
or lyophilized drug products taken as study treatment) are prohibited.

Antidiabetic medications other than metformin and study treatment (per study 
design) unless subjects require antidiabetic medication for hyperglycemic rescue.
The preferred post-rescue add-on treatment is insulin. Other medications may be 
added at the investigator’s discretion. The addition of other GLP-1 analogues (i.e., 
exenatide,  or liraglutide, lixisenatide, dulaglutide) is prohibited as the safety of 
dosing with multiple GLP 1 analogues is unknown. The use of dipeptidyl 
peptidase-IV inhibitors is prohibited. The addition of a thiazolidinedione 
(rosiglitazone or pioglitazone) is discouraged.

Any investigational drug other than the study treatment they have been randomly 
assigned to.


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
Oral or systemically injected corticosteroids (inhaled, intra-articular, epidural, and 
topical corticosteroids are allowed); short courses of oral steroids (single dose or 
multiple doses for up to 7 days) may be permitted provided these cases are 
discussed with the medical monitor
If a subject receives a prohibited medication, a protocol deviation will be reported and 
continuation in the study will be discussed with and agreed upon by the medical monitor.


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7.
STUDY ASSESSMENTS AND PROCEDURES
Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. Therefore, adherence to the study design requirements, including those 
specified in the Time and Events Table, are essential and required for study conduct.
This section lists the procedures and parameters of each planned study assessment.  The 
exact timing of each assessment is listed in the Time and Events Table Section 7.1.
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying SRM. The SRM will provide the site personnel with 
administrative and detailed technical information that does not impact subject safety.
Study visits between Baseline (Week 0) and End of treatment (Week 26) will have a visit 
window of ±3 days and the follow-up visit (Week 34) will have a visit window of ±7 
days. If extraordinary events that make it impossible for subjects to complete a 
visit/dosing within the visit window (e.g., holidays, personal emergencies), the 
investigator should contact the medical monitor for advice.  
If a subject misses a weekly scheduled visit for receiving albiglutide treatments, the 
albiglutide treatments should be administered as soon as possible within 3 days after the 
missed dose. Thereafter, subjects can resume dosing on their usual day of administration. 
If it is more than 3 days after the missed dose, the site staff should wait and administer at 
the subject’s next regularly scheduled visit.  If a subject misses 2 or more consecutive 
dosing, the investigator should contact the medical monitor to discuss options for helping 
assure better adherence.  The medical monitor shall make a decision (on a case by case 
basis) on whether the subject should continue to receive investigation product.


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7.1.
Time and Events
Table 4
Schedule of Assessments
Procedure
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Week
-2
0
1
2
3
4
5
6
7
8
9
10
11
12
Visit Window
-14d
0d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
Informed consent
X
Demography/medical history
X
HIV, hepatitis B and C, amylase, lipase, 
alcohol and drug  screen, TSH
X
Inclusion/exclusion criteria review
X
X1
Full (F) or brief (B) physical exam2
F
B
B
B
Height (H),Weigh (W), BMI 
H, W, 
BMI
W
W
12-lead ECG3
X
X
X
X
X
Vital signs3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum (S)/Urine (U) pregnancy test 
(WCBP)
S
U
U
U
U
Clinical chemistry/hematology samples4
X
X
X
X
Lipids (including total cholesterol, LDL-C, 
HDL C, triglycerides, FFAs)4
X
Urinalysis5
X
HbA1c 6,9
X
X
X
X
X
X
eGFR
X
X
X
Immunogenicity sample7
X
X
X
X
X
Genetic sample8
X
FPG 9
X
X
X
X
X
X
X
X
X
X
X
X
X
PK samples10
X
Review AE/SAE, concomitant medication 
and hypoglycemia events 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Advice on diet and exercise11
X
X
X
X
X
X
X
X
X
X
X
X
X
Register visit into IVRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization12
X
Study Treatment 
X
X
X
X
X
X
X
X
X
X
X
X
X


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Table 4
Schedule of Assessments
Procedure
Treatment
End of 
Treatment
12,13
Follow-
up14
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week15
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
Visit Window
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±7d
Informed consent
Demography/medical history
HIV, hepatitis B and C, amylase, lipase, 
alcohol and drug  screen, TSH
Inclusion/exclusion criteria review
Full (F) or brief (B) physical exam2
B
B
B
B
F
F
Height (H),Weigh (W), BMI 
W
W
W
W
W
W
12-lead ECG3
X
Vital signs
X
X
X
X
X
X
X
X
Serum (S)/Urine (U) pregnancy test (WCBP)
U
U
U
U
S
U
Clinical chemistry/hematology samples4
X
X
Lipids (including total cholesterol, LDL-C, HDL 
C, triglycerides, FFAs)4
X
X
Urinalysis
X
HbA1c 5,8
X
X
X
X
eGFR
X
X
X
Immunogenicity sample6
X
X
X
X
X
Genetic sample7
FPG 8
X
X
X
X
X
PK samples9
X
Review AE/SAE, concomitant medication and 
hypoglycemia events 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Advice on diet and exercise10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Register visit into IVRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization11
Study Treatment 
X
X
X
X
X
X
X
X
X
X
X
X
X
TSH: thyroid stimulating hormone; BMI: body mass index; WCBP: women of child bearing potential; FFA: free fatty acids; LDL-c:  low density lipoproteins cholesterol; 
HDL-c: high density lipoproteins cholesterol; d, day


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1.
Before dosing, the investigator must review all inclusion and exclusion criteria to confirm subject’s eligibility. If a subject no longer meets all of the eligibility criteria (e.g., there is 
evidence of a new myocardial infarction (MI) on an ECG or ALT, etc. are out of range), do not administer the study treatment and contact the medical monitor to discuss how to 
proceed (e.g., to determine if repeat testing is warranted). 
2.
Details of full and brief physical examinations are provided in Section 7.4.3.
3.
12-lead ECGs will be obtained before measurement of vital signs and collection of blood samples for laboratory testing. Vital signs measurement will be taken before collection of 
blood samples. See Section 7.4.5.
4.
Clinical chemistry and hematology assessments are described in Section 7.4.6.
5.
Blood samples for HbA1c should be collected before administration of study treatment.
6.
Blood samples for immunogenicity are to be collected before study drug administration at the times specified in Section 7.1.  A follow-up sample will be taken from each subject 8 
weeks after the final dose of albiglutide is administered.
7.
Blood sample for genetics can be collected at any time during the study after the genetics informed consent has been obtained and the subject has been randomly assigned to 
treatment group. 
8.
Subjects will have their FPG and HbA1c levels evaluated to monitor for potential hyperglycemia.
9.
PK samples (trough) will be obtained prior to dosing (Section 7.6).
10. Standard diabetic dietary and exercise advice will be provided at Visit 2 and reinforced through the end-of-treatment visit.
11. Once the HbA1c results have been received from the central laboratory and all other eligibility criteria are met, study centre personnel will call the IVRS to obtain the subject’s 
treatment assignment.
12. Subjects who discontinue study treatment should be handled as described in Section 5.5.
13. The end of treatment visit in Study 200952.is also Visit 1 of 204682 for those subjects continuing into the extension study.
14. Follow-up visit for those subjects who have stopped investigational product (see Section 5.5), withdrawn from the study, or who have completed the 26 week treatment period, but 
do not consent and/or are not eligible to participate in the 26 week extension study (Study 204682).
15. All visits will have a treatment window as in the table. Baseline (Week 0) serves as the reference point. Subjects will not be considered out of compliance if visit windows extend 
because of extraordinary events that make it impossible for subjects to complete a visit within the above window (e.g., holidays, vacations, personal emergencies). Determination 
of the maximum visit window deviation is at the discretion of the medical monitor


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Table 5
Schedule of Assessments for Subjects Who Permanently Discontinue Investigational Product
Procedure
Continue Scheduled Clinic Visit 
(Weeks 4, 8, 12, 16, 20) 4, 5
Week 26 
(Equivalent to End of Treatment 
Visit)
Follow-up 
Week 34
Full (F) or brief (B) physical exam
B
F
F
Weight
X
X
X
12-lead ECG 1
X
X
Vital Signs
X
X
X
Clinical chemistry/hematology samples 2
X
X
X
HbA1c and FPG 3
X
X
X
Review AE/SAE, concomitant medication and hypoglycemia 
events
X
X
X
1.
12-lead ECGs will be obtained before measurement of vital signs and collection of blood samples for laboratory testing. Vital signs measurement will be taken before collection of 
blood samples. See Section 7.4.5.
2.
Clinical chemistry and hematology assessments are described in Section 7.4.6.
3.
Subjects will have their FPG and HbA1c levels evaluated to monitor for potential hyperglycemia.
4.
Week will be dependent on when the subject discontinues investigational product. Subjects will start this schedule as soon as possible following investigational product 
discontinuation and timings of visits will be the same as for if the subject was continuing on investigational product. The timing of the clinic visits can be modified at the discretion 
of the investigator. All subjects must attend the Week 26 visit.
5.
Additional unscheduled visits will occur as medically necessary.


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7.2.
Screening and Critical Baseline Assessments
Before any study-specific procedure is performed, valid informed consent and assent as 
appropriate must be obtained.
Demography and medical history (including cardiovascular medical history/risk factors, 
T2DM history, history of other prior and concomitant medical conditions, and substance 
usage) will be assessed at screening (as detailed in the eCRF).
Critical baseline assessments will include:  HbA1c, FPG and immunogenicity.
Full details of screening and baseline assessments are provided in the Time and Events 
Table Section 7.1.
7.3.
Efficacy
HbA1c and FPG will be measured at the time points specified in the Time and Events 
Schedule in Section 7.1. Blood samples for HbA1c and FPG should be collected before 
administration of study treatment.
7.4.
Safety
Planned time points for all safety assessments are listed in the Time and Events Table 
(Section 7.1).  Unscheduled visits will occur as medically necessary. Detailed procedures 
for obtaining each assessment are provided in the SRM.
7.4.1.
Adverse Events (AE) and Serious Adverse Events (SAEs)
The definitions of an AE or SAE can be found in Appendix 5.
The investigator and their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE. 
7.4.1.1.
Time period and Frequency for collecting AE and SAE information
AEs and SAEs will be collected from the start of Study Treatment until the follow-up 
contact (see Section 7.4.1.3), at the timepoints specified in the Time and Events Table 
(Section 7.1).
Medical occurrences that begin prior to the start of study treatment but after obtaining 
informed consent may be recorded on the Medical History/Current Medical Conditions 
section of the eCRF.
Any SAEs assessed as related to study participation (e.g., protocol-mandated procedures, 
invasive tests, or change in existing therapy) or related to a GSK product will be recorded 
from the time a subject consents to participate in the study up to and including any 
follow-up contact. 


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All SAEs will be recorded and reported to GSK within 24 hours, as indicated in 
Appendix 5.
Investigators are not obligated to actively seek AEs or SAEs in former study subjects. 
However, if the investigator learns of any SAE, including a death, at any time after a 
subject has been discharged from the study, and he/she considers the event reasonably 
related to the study treatment or study participation, the investigator must promptly notify 
GSK.
NOTE: The method of recording, evaluating and assessing causality of AEs and SAEs 
plus procedures for completing and transmitting SAE reports to GSK are provided in 
Appendix 5
7.4.1.2.
Method of Detecting AEs and SAEs
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrence.  Appropriate questions include:
“How are you feeling?” 
“Have you had any (other) medical problems since your last visit/contact?” 
“Have you taken any new medicines, other than those provided in this study, since your 
last visit/contact?” 
7.4.1.3.
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator is required to proactively follow each 
subject at subsequent visits/contacts.  All SAEs and non-serious AEs of special interest 
(as defined in Section 4.6.1 and Section 7.4.1.5) will be followed until resolution, until 
the condition stabilizes, until the event is otherwise explained, or until the subject is lost 
to follow-up (as defined in Section 5.5). Further information on follow-up procedures is 
given in Appendix 5.
7.4.1.4.
Cardiovascular and Death Events
For any cardiovascular events detailed in Appendix 5 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular (CV) and Death sections of the eCRF will 
be required to be completed. These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death. 
The CV eCRF pages are presented as queries in response to reporting of certain CV 
(MedDRA) Medical Dictionary for Regulatory Activities terms. The CV information 
should be recorded in the specific cardiovascular section of the eCRF within one week of 
receipt of a CV Event data query prompting its completion. 


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The Death eCRF page is provided immediately after the occurrence or outcome of death 
is reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported.
7.4.1.5.
AEs of Special Interest
In the Phase IIIa clinical development program, AEs of special interest included several 
areas of safety related concern for the T2DM population, particularly for a GLP-1R 
agonist such as albiglutide.  
Specific eCRF pages will be used to capture additional details for the following AEs of 
special interest: 

Hypoglycemic events 

Liver events 

CV events (see Section 7.4.1.4)

Injection site reactions 

Potential systemic allergic reactions 

Pancreatitis 

MTC

Diabetic retinopathy 

Pneumonia 

Atrial fibrillation/atrial flutter 
The following additional AEs of special interest will be captured in the AE eCRF pages:

GI events

Pancreatic cancer 

Malignant neoplasms

Appendicitis
Subjects with drug hypersensitivity reactions that are not reasonably attributable to 
another cause or pancreatitis should discontinue investigational product and should not be 
rechallenged with albiglutide (see Section 5.5 for complete list of AEs of special interest 
requiring withdrawal).
7.4.1.6.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to GSK or GSK designee of SAEs and non-
serious AEs related to study treatment (even for non- interventional post-marketing 
studies) is essential so that legal obligations and ethical responsibilities towards the safety 
of subjects and the safety of a product under clinical investigation are met. 


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GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a product under clinical investigation.  GSK will 
comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) and investigators.
Investigator safety reports are prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and GSK policy and are forwarded 
to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE(s) or other 
specific safety information (e.g., summary or listing of SAEs) from GSK will file it with 
the IB and will notify the IRB/IEC, if appropriate according to local requirements.
7.4.2.
Pregnancy

If a subject becomes pregnant during the study they should discontinue 
Investigational Product.

Any pregnancy that occurs during study participation (i.e., from 
baseline/randomization through the end of the post-treatment follow-up period) 
must be reported using a clinical trial pregnancy form.
If a pregnancy is reported then the investigator should inform GSK within 2 weeks of 
learning of the pregnancy and should follow the procedures outlined in Appendix 6.
7.4.3.
Physical Exams
A full or brief physical examination will be performed at the time points specified in the 
Time and Events Table Section 7.1

A full physical examination will include, at a minimum, assessment of the skin 
(including injection site), head, eyes, ears, nose, throat, thyroid, respiratory system 
cardiovascular system, abdomen (liver and spleen), lymph nodes, central nervous 
system and extremities. 

Brief physical examination includes evaluation of skin (including injection site), 
respiratory system, cardiovascular system, abdomen (liver, spleen), and central 
nervous system 

Investigators should pay special attention to clinical signs related to previous 
serious illnesses

Height will be measured and recorded at screening only. Height should be measured 
with the subject in indoor daytime clothing with no shoes.
Weight will be measured at the time points specified in the Time and Events Table 
Section 7.1
Body mass index will be calculated at screening only.


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7.4.4.
Vital Signs
For vital signs (blood pressure and pulse rate), a single measurement will be taken at each 
clinic visit (Section 7.1). During visits when ECGs are scheduled, vital sign 
measurements will be taken after the completion of the ECG sampling. Subjects may be 
either in a semi-recumbent or seated position. During visits when ECGs are not 
scheduled, vital sign measurements will be taken while subjects are in a seated position 
after at least a 5-minute rest period. During visits where a blood draw is required, vital 
sign measurements will be taken prior to sample collection.
7.4.5.
Electrocardiogram (ECG)

A single 12-lead ECG recording (with subject in semirecumbent position for 10 to 
15 minutes before obtaining the ECG) will be performed at the time points specified 
in the Time and Events Table (Section 7.1) using an ECG machine that automatically 
calculates the heart rate and measures PR, QRS, QT, and QTc intervals.  Refer to 
Section 5.5.5 for QTc withdrawal criteria.
All ECGs will be performed before measurement of vital signs and collection of blood 
samples for laboratory testing.
Investigators must compare the baseline ECG with the Visit 1 (screening) ECG. Any 
changes indicative of a new MI or unstable cardiovascular condition (i.e., life-threatening 
arrhythmia) should prompt the investigator to not administer the investigational 
product but rather to evaluate and treat the subject per local standard of care. If 
subsequent evaluation reveals that a new MI has occurred or unstable/accelerated angina 
is documented, then the subject will not be included in the study. If subsequent evaluation 
reveals no evidence of ischemic damage or instability, then study treatment may proceed. 
If any screening ECG demonstrates a possible old MI that was unknown to the 
investigator and the subject, the subject should be evaluated and treated, as appropriate. 
7.4.6.
Clinical Safety Laboratory Assessments
All protocol required laboratory assessments, as defined in Table 6 must be conducted in 
accordance with the Laboratory Manual, and Protocol Time and Events Schedule in 
Section 7.1. Laboratory requisition forms must be completed and samples must be 
clearly labeled with the subject number, protocol number, site/centre number, and visit 
date. Details for the preparation and shipment of samples will be provided by the 
laboratory and are detailed in the laboratory manual. Reference ranges for all safety 
parameters will be provided to the site by the laboratory responsible for the assessments.
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in subject management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification) the results must be recorded in the eCRF.
Refer to the SRM for appropriate processing and handling of samples to avoid duplicate 
and/or additional blood draws.


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All study-required laboratory assessments will be performed by a central laboratory, apart 
from HbA1c at screening where a local or central laboratory may be used. HbA1c results 
from a local laboratory must be entered into the eCRF.
Hematology, clinical chemistry, urinalysis and additional parameters to be tested are 
listed in Table 6.


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Table 6
Protocol Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
Red blood cell (RBC) 
Indices:
White blood cell (WBC) count 
with Differential:
RBC Count
mean corpuscular 
volume (MCV)
Neutrophils
Hemoglobin
mean corpuscular 
hemoglobin (MCH)
Lymphocytes
Hematocrit
Monocytes
Eosinophils
Basophils
Clinical 
Chemistry 1
Blood urea 
nitrogen 
(BUN)
Potassium
Aspartate amino 
transferase (AST 
(SGOT))
Total and direct 
bilirubin
Creatinine
Sodium
ALT (SGPT)
Total Protein
Calcium
chloride
Alkaline phosphatise
Albumin
bicarbonate
Uric acid
Gamma glutamyl 
transferase (GGT)
Routine 
Urinalysis

Specific gravity

pH, glucose, protein, blood and ketones by dipstick

Microscopic examination (if blood or protein is abnormal)
Other 
Laboratory
Tests

HbA1c

FPG

Amylase2,5

Lipase2,5

HIV2

TSH2,3

Lipids including total cholesterol, LDL-C, HDL C, triglycerides, 
FFAs (fasting) 4

Hepatitis B (HBsAg) 2

Hepatitis C (Hep C antibody) 2

FSH and estradiol (as needed in women of non-child bearing 
potential only)

Alcohol and drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, cannabinoids and benzodiazepines)2

Serum  or urine hCG Pregnancy test (as needed for women of child 
bearing potential) 
1.
Details of Liver Chemistry Stopping Criteria and Required Actions and Follow-Up Assessments after liver stopping 
or monitoring event are given in Section 5.5.4 and Appendix 3.
2.
Measured at screening only.
3.
Free T4 (reflex) will be measured if TSH is above  the upper limit of normal
4.
Fasting is defined as no food or drink (except water) for at least 8 hours before blood draw
5.
Samples will be stored for calcitonin measurement in the event of MTC related events.


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All laboratory tests with values that are considered clinically significantly abnormal 
during participation in the study or within 25 days after the last dose of study treatment 
should be repeated until the values return to normal or baseline.  If such values do not 
return to normal within a period judged reasonable by the investigator, the etiology 
should be identified and the sponsor notified.
7.4.7.
Estimated Glomerular Filtration Rate (eGFR)
Serum creatinine will be measured at the time points specified in Time and Events 
Schedule in Section 7.1. It will be used to calculate eGFR using the MDRD formula 
[Levey, 2009], namely:
eGFR (ml/min/1.73m2) = 175 x (serum creatinine)-1.154 x (Age)-0.203 x (0.742 if female) x 
(1.212 if African American).
7.4.8.
Diabetic Dietary, Exercise, and Home Plasma Glucose Monitoring 
Advice
Standard diabetic dietary, exercise, and home blood glucose monitoring advice as well as 
on the signs and symptoms of hypoglycemia and on supplemental oral glucose treatment 
will be provided at Visit 2 (Week 0) and reinforced at each study site visit through the 
End of Treatment Visit (Week 26). Subjects should monitor the blood glucose as per the 
instructions of the investigator and as appropriate for their medical management. The 
subjects should report promptly, as directed by the investigator, the occurrence of 
hyperglycemia or hypoglycemia (particularly if symptomatic) to the investigator (or his 
or her designee). Assessment and action should then occur as deemed appropriate by the 
investigator.
7.4.9.
Hypoglycemic Events
Specific criteria for monitoring hypoglycemic events have been designed to ensure 
subject safety and to closely monitor hypoglycemia. Hypoglycemic events are defined as 
follows [Seaquist, 2013]:
Severe Hypoglycemia

Severe hypoglycemia is an event requiring assistance of another person to actively 
administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose 
concentrations may not be available during an event, but neurological recovery 
following the return of plasma glucose to normal is considered sufficient evidence 
that the event was induced by a low plasma glucose concentration. 
Documented Symptomatic Hypoglycemia

Documented symptomatic hypoglycemia is an event during which typical symptoms 
of hypoglycemia are accompanied by a measured plasma glucose concentration 70 
mg/dL (3.9 mmol/L). 


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Asymptomatic Hypoglycemia

Asymptomatic hypoglycemia is an event not accompanied by typical symptoms of 
hypoglycemia but with a measured plasma glucose concentration 70 mg/dL 
(3.9 mmol/L). 
Probable Symptomatic Hypoglycemia

Probable symptomatic hypoglycemia is an event during which symptoms typical of 
hypoglycemia are not accompanied by a plasma glucose determination but that was 
presumably caused by a plasma glucose concentration 70 mg/dL (3.9 mmol/L). 
Pseudohypoglycemia

Pseudohypoglycemia is an event during which the person with diabetes reports any 
of the typical symptoms of hypoglycemia with a measured plasma glucose 
concentration >70 mg/dL (>3.9 mmol/L) but approaching that level. 
Any hypoglycemic event, regardless of intensity, that satisfies the definition of an SAE 
(Appendix 5) should be categorized as outlined in this section and reported appropriately 
in the SAE eCRF page and the hypoglycemic events AE of special interest page.
7.5.
Tracking of Albiglutide Lyophilized DCC Pen Injector and 
Liquid Auto-injector Failures and User Errors
All albiglutide lyophilized product DCC pen injector and liquid product auto-injector 
failures and user errors must be detected, documented, and reported by the investigator 
throughout the study. Detailed information on DCC pen injector and auto-injector failures 
and user errors will be collected on the Injector Pen and Auto-injector Failure Reporting 
Form.
NOTE: Albiglutide lyophilized DCC pen injector and liquid auto-injector failures and 
user errors associated with or resulting in events fulfilling the definition of an AE or SAE 
will follow the processes outlined in Section 7.4.1.
7.6.
Pharmacokinetics
7.6.1.
Blood Sample Collection
Blood samples for the determination of albiglutide plasma concentrations will be 
obtained from all subjects before administration of study treatment according to the Time 
and Events Table in Section 7.1.During visits where ECGs and vital sign measurements 
are required, blood samples will be collected after measurement of ECGs and vital signs.
Blood samples will be collected and stored as detailed in the Laboratory Manual.


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7.6.2.
Sample Analysis
Plasma analysis will be performed under the control of PTS-DMPK, GlaxoSmithKline, 
the details of which will be included in the Study Reference Manual (SRM). 
Concentrations of albiglutide will be determined in plasma samples using the currently 
approved bioanalytical methodology. Raw data will be archived at the bioanalytical site 
(detailed in the SRM).
Once the plasma has been analyzed for albiglutide, any remaining plasma may be 
analyzed for other compound-related metabolites and the results reported under a 
separate PTS-DMPK, GlaxoSmithKline protocol.
7.7.
Immunogenicity
Serum for antidrug antibody testing will be obtained from all subjects before 
administration of study treatment  at week 0, 2, 4, 8, 12, 16, 20, 24, 26 and at follow-
up(wk 34, if applicable),according to the Time and Events Table in Section 7.1
The presence of anti-albiglutide antibodies will be assessed using a validated enzyme-
linked immunosorbent assay. The assay involves screening, confirmation, and titration 
steps (tiered-testing approach). Confirmed positive samples will be titrated to obtain the 
titre of antibodies and tested for GLP-1 and albumin cross-reactivity, as well as for 
albiglutide neutralizing activity. Samples positive for both anti-GLP-1 antibodies and 
drug neutralizing antibodies may be tested for GLP-1 neutralizing activity (Appendix 7).
Additionally, in the case of severe allergic reactions that include anaphylaxis, 
angioedema, or other severe potential hypersensitivity reactions, three 1-mL serum 
samples should be obtained for immunogenicity testing (within 24 hours of the event if 
possible) and sent to the central  laboratory (see details in the SRM) for immediate 
distribution to a contracted testing facility for specific immunological testing (albiglutide-
specific IgE and other tests, as appropriate)  A follow-up serum sample will be collected 
8 weeks after the final dose of study treatment in the case of early withdrawal from the 
study.
For subjects who have discontinued study treatment or subjects who have completed the 
26 week treatment period, but do not consent and/or are not eligible to participate in the 
26 week extension study (Study 204682), if baseline antibody levels or a reduction in 
titer are not achieved by the follow-up visit then additional samples for immunogenicity 
testing may be obtained every 30 days following the follow-up visit until baseline 
antibody levels, or reduced titres, are achieved. Subjects eligible for the extension study 
(Study 204682) will have immunogenicity samples taken as specified in protocol 204682.
7.8.
Genetics
Information regarding genetic research is included in Appendix 4.


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8.
DATA MANAGEMENT
For this study, subject data will be entered via an eCRF into Oracle Clinical Remote Data 
Capture (OC RDC) system. Subject data will be available for viewing through access to 
the OC RDC system. Data provided from other sources will be received, reconciled, 
combined and transferred to GSK at predetermined time points.
Management of clinical data will be performed in accordance with applicable PPD 
standards and data cleaning procedures to ensure the integrity and quality of the data, 
e.g., removing errors and inconsistencies in the data. Adverse events and concomitant 
medication terms will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) and a validated medication dictionary GSKDrug.
The eCRFs (including queries and audit trails) will be sent at the end of the study in CD 
format to GSK to be retained. Each investigator will receive a copy of their site specific 
data in the same format to maintain as the investigator copy. In all cases, subject initials 
will not be collected or transmitted.
9.
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
9.1.
Hypotheses
The primary hypothesis is to test that liquid drug product will provide glycemic control 
(as measured by HbA1c change from baseline) non-inferior to lyophilized drug product 
for a period of 26 weeks of treatment in subjects with T2DM.
9.2.
Sample Size Considerations
9.2.1.
Sample Size Assumptions
This study will randomly assign approximately 150 subjects to each of the 2 treatment 
groups (liquid drug product and lyophilized drug product) in a 1:1 ratio, for a total of 
approximately 300 subjects. Eligible subjects will be stratified by age (<65 or ≥65 years 
of age), weight (<90 kg or ≥90 kg), and background antidiabetic therapy (diet and 
exercise or stable dose of metformin).  
With 133 subjects in each of the 2 treatment groups, the study will provide 90% power to 
demonstrate non-inferiority for HbA1c change from baseline, assuming a non-inferiority 
margin of 0.4%, an expected treatment group difference of 0.0%, and a common standard 
deviation of 1%, using a 2-sample, 1-sided t test with significance level of 0.025. Power 
was calculated using PASS [Hintze, 2013]. Assuming that 13% of subjects will be 
withdrawn early or will be lost to follow-up; therefore, approximately 150 subjects will 
be randomized in each treatment group. 
The non-inferiority margin of 0.40 was selected based on the expected effect of the 
albiglutide lyophilized drug product as active control. Results from two HARMONY 


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Phase III studies (subset of GLP112756 and GLP112753) for the comparison of the 
control albiglutide lyophilized drug product versus placebo were used in selecting the 
non-inferiority margin. The two studies are similar to the current study in terms of the 
population and the design; subjects were either on diet and exercise or metformin 
background therapy and received 30 mg of albiglutide then up-titrated to 50 mg 
albiglutide. The 95% confidence interval from the 2 Harmony studies for HbA1c change 
from baseline at week 24 for albiglutide lyophilized drug product difference from placebo 
is ( -1.04, -0.75). The conservative effect in terms of the difference from placebo for 
HbA1c change from baseline at Week 24 for albiglutide lyophilized drug product versus 
placebo is 0.75% (M1 =0.75%, as defined in Guidance for Industry: Non-Inferiority 
Clinical Trials [FDA, 2010]).  M2, calculated as 50% of M1 is 0.375 (approximately 0.4). 
The margin of 0.40% that should be met in this trial will preserve at least 45% of the 
effect of the comparator and it is below M1.
9.2.2.
Sample Size Sensitivity
Figure 2  illustrates the power versus standard deviation of 0.7, 0.8, 0.9, 1.0, 1.1, and 1.2 
to reject the null hypothesis of inferiority for HbA1c change from baseline, assuming a 
non-inferiority margin of 0.4%, an expected treatment group difference of 0.0%, and a 
sample size of 133 per treatment group, using a 2-sample, 1-sided t- test with a 
significance level of 0.025.
Figure 2
Power of non-inferiority testing for HbA1c different values of 
Standard Deviations (S1) of 0.7, 0.8, 0.9, 1.0, 1.1, and 1.2
9.2.3.
Sample Size Re-estimation or Adjustment
No sample size re-estimation is planned for this study.


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9.3.
Data Analysis Considerations
9.3.1.
Analysis Populations
Intent-to-Treat (ITT) Population:  The ITT Population will include all randomized 
subjects who receive at least 1 dose of the study medication and have a baseline 
assessment. The ITT population will be analyzed according to the randomly assigned 
treatment. The ITT Population is the primary population for all efficacy analyses.
Safety Population:  The Safety Population is defined as all enrolled subjects who receive 
at least 1 dose of study medication. The subjects in the Safety Population will be 
analyzed according to the treatment received. The Safety Population will be used for all 
safety analyses.
Per-Protocol (PP) Population: The PP Population will include all subjects randomly 
assigned to treatment who complete study procedures through Week 26 and are 
compliant with the protocol. The subjects in the PP Population will be analyzed 
according to randomized treatment. The PP Populations may be used for supportive 
analyses of the efficacy endpoints.
Other analysis populations will be defined in the reporting and analysis plan (RAP).
9.3.2.
Interim Analysis
No interim analysis is planned for this study.
9.4.
Key Elements of Analysis Plan
9.4.1.
Primary Analyses
The primary endpoint is the change from baseline in HbA1c at Week 26. The primary 
analysis will include all HbA1c values collected at scheduled visits up to Week 26. This 
will include values after hyperglycemia rescue and discontinuation from investigational 
product. The primary analysis of the primary endpoint will be conducted using a mixed-
effect model with repeated measures (MMRM) in the ITT Population. MMRM will use 
all available data.  Imputation under the non-inferiority null hypothesis for missing data 
will be incorporated [Koch, 2008]. Multiple imputation will be used to replace missing 
data of change from baseline of HbA1c at Week 26 for all patients in both treatment arms 
as a first step, and then to make all the imputed values for the liquid drug product arm 
worse by the non-inferiority margin 0.4. 
Multiple imputation approach uses separate covariance parameter estimation for each 
arm, and also separate regression parameters are estimated on baseline covariates within 
each arm. For subjects with missing data the imputation will use means and variances-
covariances from subjects in that treatment group where that subject with missing data 
belongs. This approach will be used for all data missing post withdrawal due to lost to 
follow-up or withdraws consent.


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Non-inferiority testing will be performed at a one-sided alpha of 0.025 and non-
inferiority margin of 0.4. 
Further details of the imputation method for the primary analysis will be provided in the 
RAP.
The primary MMRM model will include HbA1c change from baseline at all post-baseline 
visits as dependent variables; treatment, region, age category, weight, background 
antidiabetic therapy, visit week, and treatment-by-week interaction as fixed effects; 
baseline HbA1c as a continuous covariate; and subject as a random effect. Treatment 
effects estimates (and associated CI) of albiglutide liquid drug product will be evaluated 
within this MMRM model as least squares means contrasts relative to the lyophilized 
drug product. An unstructured covariance matrix will be used for the MMRM analysis, 
unless the model does not converge, in which case the covariance matrix will be decided 
upon model convergence status and the Akaike information criterion. 
9.4.2.
Secondary Analyses
The evaluation of the safety and tolerability as assessed by immunogenicity and ISRs of 
albiglutide liquid drug product and the lyophilized drug product will be provided by 
reporting the event rates, and the associated 95% CI.
The overall general safety and tolerability of albiglutide liquid drug product versus 
lyophilized drug product will be evaluated in tabular and/or graphical format and 
summarized descriptively. 
AEs and SAEs, physical examinations, clinical laboratory evaluations, vital sign 
measurements, and 12-lead electrocardiogram will be summarized by treatment group. 
For continuous variables, these summaries will include sample size, mean, median, 
standard deviation (and/or standard error), minimum, and maximum. For categorical 
variables, the summaries will include frequencies and corresponding percentages. The 
exposure-adjusted incidence rate will also be calculated as the number of events in a 
given period divided by the total person time on treatment of subjects at risk within the 
same period. The exposure-adjusted incidence rate will be expressed as an annualized 
rate expected.  No inferential testing will be performed on the safety variables. 
Hypoglycemic events will be analyzed separately from other AEs. All hypoglycemic 
events will be classified as severe, documented symptomatic, asymptomatic, probable 
symptomatic, and pseudohypoglycemia, as defined in Section 7.4.9.
AEs will be coded using MedDRA. AEs will be summarized in various subsets, including 
on therapy AEs, related AEs, AEs leading to treatment discontinuation or withdrawal 
from study, SAEs, fatal AEs, etc. AEs will also be summarized by maximum intensity
(mild, moderate, and severe).
Anti-albiglutide antibody results will be summarized by treatment group. In addition, the 
number and percentage of subjects with positive results along with the antibody titer 
values will be provided by visit. 


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The secondary endpoint FPG change from baseline at Week 26 will be analyzed using 
MMRM without imputation.
To assess the PD effect of albiglutide over time for the secondary endpoints change from 
baseline in HbA1c over time and change from baseline in FPG over time MMRM models 
will be used. The model will include HbA1c or FPG change from baseline at all post-
baseline visits as dependent variables; treatment, visit week, and treatment-by-week 
interaction as fixed effects; baseline HbA1c or FPG as a continuous covariate; and 
subject as a random effect. Treatment effects estimates (and associated CI) of albiglutide 
liquid drug product will be evaluated within this MMRM model as least squares means 
contrasts relative to the lyophilized drug product. An unstructured covariance matrix will 
be used for the MMRM analysis, unless the model does not converge, in which case the 
covariance matrix will be decided upon model convergence status and the Akaike 
information criterion. In addition, PD effect of albiglutide over time for both HbA1c and 
FPG change from baseline over time will be evaluated in tabular and/or graphical format 
and summarized descriptively.
PK trough plasma concentration data will be summarized by treatment. No formal 
statistical analyses will be conducted.
9.4.3.
Other Analyses
The analyses of the primary and secondary efficacy endpoints are described in Section 
9.4.1 and Section 9.4.2. The details of any further planned analyses, including subgroup 
analysis and exploratory endpoints, will be provided in the RAP.
9.4.4.
Supportive Analyses for Primary Endpoint
The primary endpoint change from baseline in HbA1c at Week 26 will be analyzed using 
the same MMRM model as described in Section 9.4.1 but missing data are not explicitly 
imputed in this supportive analysis; although, there is an underlying assumption that data 
is missing at random. All available scheduled post-baseline assessments up to endpoint 
are utilized and, via modeling of the within subject correlation structure, the derived 
treatment difference at Week 26 is adjusted to take into account missing data. The 
MMRM analysis (using saturated fixed effects and an unstructured variance-covariance 
matrix) is considered appropriate as the supportive analyses, as it has been shown to give 
sensible answers to on-treatment questions in a range of practical situations [Siddiqui, 
2009].
Analysis excluding post-rescue and/or discontinuation from investigational product 
HbA1c data will also be performed as supportive.  It is not expected to have a substantial 
number of subjects who will require rescue and that number of subjects would be similar 
for both treatment arms.  However, to assess the impact of rescue, analysis of pre-rescue 
data will be performed. The MMRM model will be similar to the one used for the 
primary analysis.  Results of this analysis will supplement the primary analysis. No 
imputation will be conducted for this supportive analysis.


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The primary endpoint HbA1c change from baseline at Week 26 may also be analyzed 
using MMRM model in the PP Population, if sample size is sufficient, imputation will 
not be conducted for this supportive analysis. 
Further details of the supportive analyses will be provided in the RAP.
9.4.5.
Missing Data
9.4.5.1.
Impact of Missing Data on Primary Endpoint
Missing data, in the context of the primary analysis at Week 26, refer to those cases 
where the Week 26 HbA1c value is not available or was not collected or subject is lost to 
follow-up or withdraws consent. Missing data will be imputed in the primary MMRM 
analysis. To avoid bias in non-inferiority trials due to missing data, special attention will 
be paid to the handling of missing data in statistical analysis. Although, it is expected that 
the pattern of missing data will be similar in both treatment arms given that the treatment 
arms are the same drug but different formulations and it is expected that the impact of 
missing data on the primary endpoint to be minimal. Imputation under the non-inferiority 
null hypothesis [Koch, 2008] for all missing data for the primary analysis at Week 26 will 
be implemented.
9.4.5.2.
Extent of Missing Primary Analysis Data
Missing data is expected to arise mainly from subjects missing complete visits. The 
amount of missing data for those baseline covariates included in the statistical analysis is 
expected to be none or at worst minimal. If it should occur, that subject will effectively 
be lost to analysis. Missing data for HbA1c between two non-missing visits will be 
considered missing at random (intermediate missing data).
In this study, subjects who withdraw from treatment will stay in the study. In the eCRF, 
the reason for treatment discontinuation and the reason for withdrawal from the study are 
collected separately. Whenever the HbA1c value at Week 26 is missing (end of the 
study), the reason can be determined based on available data in these two locations.
The reason for missing data can be classified as lost to follow-up or withdrawal of 
consent.
9.4.5.3.
Reasons for Withdrawal
Reasons for withdrawal from the study are lost to follow-up or withdrawal consent.  All 
subjects who discontinuation from investigational product due to the reasons listed under 
Section 5.5 will remain in the study and efficacy and safety data will be collected.
9.4.5.4.
Handling of Missing Data
The impact of missing data will be explored, as outlined below, for the ITT Analysis 
Population only.


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Examination of Missing Data Patterns
It is expected that the pattern of missing data will be similar in both treatment arms given 
that each treatment arm is using the same drug but different formula. 
To examine the nature of missing data, due to lost to follow-up or withdrawal consent, 
cohorts of subjects will be defined based on the scheduled assessments (HbA1c change 
from baseline) that were completed at Weeks 1, 4, 8, 12, 16, 20, and 26.

Subjects who have week 1 assessment only

Subjects who have assessments up to and including Week 4 only

Subjects who have assessments up to and including Week 8 only

Subjects who have assessments up to and including Week 12 only

Subjects who have assessments up to and including Week 16 only

Subjects who have assessments up to and including Week 20 only

Subjects who have assessments up to and including Week 26.
The number and percentage of subjects on each treatment in the 7 cohorts defined here 
will be tabulated. Graphical methods will be used to examine changes from baseline over 
time to assess the pattern of outcomes prior to withdrawal.
Sensitivity Analyses 
The sensitivity of the results of analysis to the method of handling missing values will be 
investigated, especially if the number of missing values is substantial or if the 
characteristics of missing values differ between treatment groups. 
To assess the impact of subjects who discontinued investigational product and stayed in 
the study; exclusion of data after treatment discontinuation may also be performed if a 
significant number of subjects discontinue study medication prior to Week 26. On 
treatment data will be analyzed using MMRM model as described in Section 9.4.1.  
Week 26 observations off-treatment will be imputed under the non-inferiority null 
hypothesis [Koch, 2008].
Sensitivity analyses using a different type of multiple imputation method will be 
conducted. Firstly, missing data between two non-missing time points will be considered 
missing at random (MAR). The analyses using the last mean carried forward (LMCF) 
approach will be performed using the following rates of HbA1c increase: 0%/month, 
0.1%/month, and 0.2%/month to explore the potential impact as in a tipping-point 
analysis. For each treatment group, these 3 rates will be assumed, resulting in 9 scenarios. 
The resulting treatment differences and associated P-values for non-inferiority will be 
tabulated against the varying rates of HbA1c increase. This estimand is one where those 
who withdraw are assumed to revert to an unstable treatment regimen with an increasing 
rate of HbA1c. For each imputation data set, an analysis of variance will be carried using 
Week 26 data, both actual and imputed, using the same covariates as in the primary 


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analysis. Contrasts of interest will be estimated and then combined across imputations 
using standard multiple imputation rules.
10.
STUDY GOVERNANCE CONSIDERATIONS
10.1.
Posting of Information on Publicly Available Clinical Trial
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
10.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Prior to initiation of a site, GSK will obtain favorable opinion/approval from the 
appropriate regulatory agency to conduct the study in accordance with ICH (International 
Conference on Harmonization) Good Clinical Practice (GCP) and applicable country-
specific regulatory requirements.
The study will be conducted in accordance with all applicable regulatory requirements, 
and with GSK policy.
The study will also be conducted in accordance with ICH GCP, all applicable subject 
privacy requirements, and the guiding principles of the current version of the Declaration 
of Helsinki.  This includes, but is not limited to, the following:

IRB/IEC review and favorable opinion/approval of the study protocol and 
amendments as applicable

Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IRB/IEC)

GSK will provide full details of the above procedures, either verbally, in writing, 
or both.

Signed informed consent must be obtained for each subject prior to participation in 
the study (and for amendments as applicable).

The IEC/IRB, and where applicable the regulatory authority, approve the clinical 
protocol and all optional assessments, including genetic research.  

Optional assessments (including those in a separate protocol and/or under separate 
informed consent) and the clinical protocol should be concurrently submitted for 
approval unless regulation requires separate submission.  

Approval of the optional assessments may occur after approval is granted for the 
clinical protocol where required by regulatory authorities.  In this situation, written 
approval of the clinical protocol should state that approval of optional assessments 
is being deferred and the study, with the exception of the optional assessments, can 
be initiated.


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10.3.
Quality Control (Study Monitoring)

In accordance with applicable regulations including good clinical practice (GCP), 
and GSK procedures, GSK monitors will contact the site prior to the start of the 
study to review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK requirements.  

When reviewing data collection procedures, the discussion will also include 
identification, agreement and documentation of data items for which the eCRF will 
serve as the source document.
GSK will monitor the study and site activity to verify that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements.
The investigator and the head of the medical institution (where applicable) agrees to 
allow the monitor direct access to all relevant documents
10.4.
Quality Assurance

To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and 
the regulatory agencies may conduct a regulatory inspection at any time during or 
after completion of the study. 

In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss 
the conduct of the study, any findings/relevant issues and to implement any 
corrective and/or preventative actions to address any findings/issues identified.
10.5.
Study and Site Closure

Upon completion or premature discontinuation of the study, the GSK monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSK Standard 
Operating Procedures.

GSK reserves the right to temporarily suspend or prematurely discontinue this 
study at any time for reasons including, but not limited to, safety or ethical issues 
or severe non-compliance. For multicenter studies, this can occur at one or more or 
at all sites.  

If GSK determines such action is needed, GSK will discuss the reasons for taking 
such action with the investigator or the head of the medical institution (where 
applicable).  When feasible, GSK will provide advance notification to the 


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investigator or the head of the medical institution, where applicable, of the 
impending action.

If the study is suspended or prematurely discontinued for safety reasons, GSK will 
promptly inform all investigators, heads of the medical institutions (where 
applicable) and/or institution(s) conducting the study. GSK will also promptly 
inform the relevant regulatory authorities of the suspension or premature 
discontinuation of the study and the reason(s) for the action.  

If required by applicable regulations, the investigator or the head of the medical 
institution (where applicable) must inform the IRB/IEC promptly and provide the 
reason for the suspension or premature discontinuation.
10.6.
Records Retention

Following closure of the study, the investigator or the head of the medical 
institution (where applicable) must maintain all site study records (except for those 
required by local regulations to be maintained elsewhere), in a safe and secure 
location.  

The records must be maintained to allow easy and timely retrieval, when needed 
(e.g., for a GSK audit or regulatory inspection) and must be available for review in 
conjunction with assessment of the facility, supporting systems, and relevant site 
staff.  

Where permitted by local laws/regulations or institutional policy, some or all of 
these records can be maintained in a format other than hard copy (e.g., microfiche, 
scanned, electronic); however, caution needs to be exercised before such action is 
taken.  

The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, 
including re-generating a hard copy, if required.  Furthermore, the investigator 
must ensure there is an acceptable back-up of these reproductions and that an 
acceptable quality control process exists for making these reproductions.

GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements.  The minimum retention time 
will meet the strictest standard applicable to that site for the study, as dictated by 
any institutional requirements or local laws or regulations, GSK 
standards/procedures, and/or institutional requirements.  

The investigator must notify GSK of any changes in the archival arrangements, 
including, but not limited to, archival at an off-site facility or transfer of ownership 
of the records in the event the investigator is no longer associated with the site.


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10.7.
Provision of Study Results to Investigators, Posting of 
Information on Publically Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location.
GSK will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
GSK will provide the investigator with the randomization codes for their site only after 
completion of the full statistical analysis.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy.
10.8.
Review Committees
A PAC composed of independent specialists in gastroenterology will review cases of 
possible pancreatitis. Details of this committee and case adjudication will be described in 
a separate charter.


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11.
REFERENCES
American Diabetes Association (ADA). Diagnosis and classification of diabetes mellitus. 
Diabetes Care, 2014; 37 (Suppl 1): S81-S90.
Egan AG, Blind E, Dunder K, de Graeff PA, Hummer BT. Pancreatic safety of incretin-
based drugs—FDA and EMA assessment. N Engl J Med. 2014; 370(9):794-7. 
European Public Assessment Report (EPAR) for Eperzan. 2014. Available at: 
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/00273
5/human_med_001735.jsp&mid=WC0b01ac058001d124
FDA Summary Basis of Approval. 2014. Available at: 
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/125431Orig1s000TOC.cfm
Food and Drug Administration (FDA). Guidance for Industry. Non-Inferiority Clinical 
Trials. U.S. Department of Health and Human Services. Food and Drug Administration. 
Center for Drug Evaluation and Research (CDER). Center for Biologics Evaluation and 
Research (CBER). March 2010 Clinical/Medical. Available from: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM202140.pdf (Accessed 12 Apr 2015).
Gautier JF, Fetita S, Sobngwi E and Salaun-Martin C. Biological actions of the incretins 
GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes 
Metab. 2005; 31(3 Pt 1):233-42.
Hintze, J. PASS 12. NCSS, LLC. Kaysville, Utah, USA. 2013. Available at 
http://www.ncss.com.
Khunti K, Andersen M, Wolden ML, Davies MJ and Thorsted BL. Clinical Inertia in 
People With Type 2 Diabetes. Diabetes Care. 2013; 36:3411-3417
Koch, G. Comments on ‘Current issues in non-inferiority trials’. Statistics in Medicine. 
2008; 27: 333-342
Levey AS, Stevens LA, Schmid CH, Zhang Y, Castro AF, Feldman HI, et al. A new 
equation to estimate glomerular filtration rate.  Ann Intern Med. 2009; 150: 604-12.
Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia 
and diabetes:  a report of a workgroup of the American Diabetes Association and the 
Endocrine Society. Diabetes Care. 2013; 36:1384-95.
Siddiqui O, Hung HM, O’Neill R. MMRM vs. LOCF: a comprehensive comparison 
based on simulation study and 25 NDA datasets. J Biopharm Stat. 2009;19 (2):227-46.
World Health Organization (WHO). Diabetes Fact Sheet. October 2013. Available at 
http://www.who.int/mediacentre/factsheets/fs312/en/ (Accessed Nov20, 2014).


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12.
APPENDICES
12.1.
Appendix 1: Abbreviations and Trademarks
Abbreviations
ADA
American Diabetes Association
AE
adverse event
ALT (SGPT)
alanine aminotransferase (serum glutamic pyruvic 
transaminase)
AST (SGOT)
aspartate aminotransferase (serum glutamic oxaloacetic 
transaminase)
BMI
body mass index
BUN
blood urea nitrogen
CI
confidence interval
CONSORT
Consolidated Standards of Reporting Trials
CPK
creatine phosphokinase
CV
cardiovascular
DCC
dual chamber cartridge
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
ELISA
enzyme-linked immunosorbent assay
EMA
European Medicines Agency
FDA
US Food and Drug Administration
FFA
free fatty acids
FPG
fasting plasma glucose
FRP
females of reproductive potential
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GCSP
Global Clinical Safety and Pharmacovigilance
GGT
gamma glutamyl transferase
GI
gastrointestinal
GLP-1
glucagon-like peptide-1
GSK
GlaxoSmithKline
HA
human albumin
HbA1c
glycated hemoglobin
HBcAb
hepatitis B core antibody 
HBsAg
hepatitis B surface antigen
HIV
human immunodeficiency virus
hCG
human chorionic gonadotrophin
HDL-c
high density lipoproteins
HRP
horseradish peroxidase
HRT
hormone replacement therapy
IB
Investigator’s Brochure
ICH
International Conference on Harmonization


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IEC
Independent Ethics Committee
INR
international normal range
IP
investigational product
IRB
Institutional Review Board
ISRs
injection site reactions
ITT
intent-to-treat
IVRS
Interactive Voice Response System
LDH
lactate dehydrogenase
LDL-c
low density lipoproteins; 
LMCF
last mean carried forward
K2EDTA
di-potassium ethylenediaminetetraacetic acid
MACE
major adverse cardiovascular event
MAR
missing at random
MCH
mean corpuscular hemoglobin
MCV
mean corpuscular volume
MDRD
Modification of Diet in Renal Disease
MedDRA
Medical Dictionary for Regulatory Activities
MEN-2
multiple endocrine neoplasia type 2
MI
myocardial infarction
MMRM
mixed-effect model with repeated measures
MNAR
missing not at random
MSDS
Material Safety Data Sheet
MTC
medullary thyroid cancer
OC RDC
Oracle Clinical Remote Data Capture
PAC
Pancreatitis Adjudication Committee
PD
pharmacodynamics
PK
pharmacokinetics
PP
per protocol
PTS-DPMK
Platform Technologies and Science-Drug Metabolism and 
Pharmacokinetics
RAP
Reporting Analysis Plan
RBC
red blood cell
RNA
ribonucleic acid
s.c.
subcutaneous
SAE
serious adverse event
SmPC
Summary of Product Characteristics
SRM
Study Reference Manual
SU
sulfonylureas
T2DM
type 2 diabetes mellitus
TSH
thyroid stimulating hormone
ULN
upper limit of normal range
WBC
white blood cell
WCBP
women of child bearing potential


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Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
MedDRA
SpectraMAX


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12.2.
Appendix 2: GSK Modified List of Highly Effective Methods 
for Avoiding Pregnancy in Females of Reproductive 
Potential (FRP)
19. Contraceptive subdermal implant that meets effectiveness criteria including a <1% 
rate of failure per year, as stated in the product label.
20. Intrauterine device or intrauterine system that meets effectiveness criteria including a 
<1% rate of failure per year, as stated in the product label [Trussell, 2011]
21. Oral Contraceptive, either combined or progestogen alone [Trussell, 2011] 
22. Injectable progestogen [Trussell, 2011]
23. Contraceptive vaginal ring [Trussell, 2011]
24. Percutaneous contraceptive patches [Trussell, 2011]
25. Male partner sterilization prior to the female subject's entry into the study, and this 
male is the sole partner for that subject. The information on the male sterility can 
come from interview with the subject on her male partner’s medical history.
26. Male condom combined with a female diaphragm, with or without a vaginal 
spermicide (foam, gel, film, cream, or suppository).
These allowed methods of contraception have a failure rate of less than 1% per year but 
are only effective when used consistently, correctly and in accordance with the product 
label.  The investigator is responsible for ensuring that subjects understand how to 
properly use these methods of contraception.
References
Trussell J, Contraceptive Efficacy. In: Hatcher RA, Trussell J, Nelson AL, Cates W, 
Kowal D, and Policar M (editors). Contraceptive Technology: Twentieth Revised 
Edition. New York: Ardent Media, 2011.Table 26-1


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12.3.
Appendix 3: Liver Safety Required Actions and Follow up 
Assessments
Phase III-IV liver chemistry stopping and increased monitoring criteria have been 
designed to assure subject safety and evaluate liver event etiology (in alignment with the 
FDA premarketing clinical liver safety guidance).  
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM174090.pdf
Phase III-IV liver chemistry stopping criteria and required follow up assessments 
Liver Chemistry Stopping Criteria - Liver Stopping Event
ALT-absolute
ALT 8xULN
ALT Increase
ALT 5xULN but <8xULN  persists for 2 weeks
ALT 3xULN but <5xULN  persists for 4 weeks
Bilirubin1, 2
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) 
INR2
ALT 3xULN and INR>1.5, if INR measured
Cannot 
Monitor
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks
Symptomatic3
ALT  3xULN associated with symptoms (new or worsening) believed to be 
related to  liver injury or hypersensitivity
Required Actions and Follow up Assessments following ANY Liver Stopping Event
Actions
Follow Up Assessments

Immediately discontinue  study treatment 

Report the event to GSK within 24 hours

Complete the liver event eCRF and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2

Perform liver event follow up assessments 

Monitor the subject until liver chemistries 
resolve , stabilize, or return to within baseline 
(see MONITORING below)

Viral hepatitis serology4

Only in those with underlying chronic 
hepatitis B at study entry (identified by 
positive hepatitis B surface antigen) 
quantitative hepatitis B DNA and hepatitis 
delta antibody5.

Blood sample for PK analysis, obtained 
within 3 half-lives (15 days) after last dose6

Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH).


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Liver Chemistry Stopping Criteria - Liver Stopping Event

Do not restart/rechallenge subject with 
study treatment 

If restart/rechallenge not  allowed or not 
granted, permanently discontinue study 
treatment and may continue subject in the 
study for any protocol specified follow up 
assessments
MONITORING:
For bilirubin or INR criteria:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within  24 
hrs

Monitor subjects twice weekly until liver 
chemistries resolve, stabilize or return to 
within baseline

A specialist or hepatology consultation is 
recommended
For All other criteria:

Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within  24-
72 hrs 

Monitor subjects weekly until liver 
chemistries resolve, stabilize or return to 
within baseline

Fractionate bilirubin, if total 
bilirubin2xULN

Obtain complete blood count with 
differential to assess eosinophilia

Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form

Record use of concomitant medications on 
the concomitant medications report form
including acetaminophen, herbal 
remedies, other over the counter 
medications.

Record alcohol use on the liver event 
alcohol intake case report form
For bilirubin or INR criteria:

Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total immunoglobulin G (IgG or gamma 
globulins).

Serum acetaminophen adducts HPLC 
assay (quantifies potential acetaminophen 
contribution to liver injury in subjects with 
definite or likely acetaminophen use in the 
preceding week [James, 2009]). NOTE: 
not required in China

Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver 
disease; complete Liver Imaging and/or 
Liver Biopsy eCRF forms.
1.
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that subject if ALT 3xULN and bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.
2.
All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, if INR 
measured which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding 


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studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold value stated 
will not apply to subjects receiving anticoagulants
3.
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia)   
4.
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis C 
ribonucleic acid (RNA); Cytomegalovirus IgM antibody;  Epstein-Barr viral capsid antigen IgM antibody (or if 
unavailable, obtain heterophile antibody or monospot testing);  Hepatitis E IgM antibody 
5.
If hepatitis delta antibody assay cannot be performed,, it can be replaced with a PCR of hepatitis D RNA virus 
(where needed) [Le Gal, 2005].
6.
PK sample may not be required for subjects known to be receiving placebo or non-GSK comparator treatments.  
Record the date/time of the PK blood sample draw and the date/time of the last dose of study treatment prior to 
blood sample draw on the eCRF. If the date or time of the last dose is unclear, provide the subject’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected in 
the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the SRM.  
Phase III-IV liver chemistry increased monitoring criteria with continued therapy
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event
Criteria
Actions
ALT 5xULN and <8xULN and
bilirubin <2xULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 2 weeks.
OR
ALT 3xULN and <5xULN and
bilirubin <2xULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 4 weeks.

Notify the GSK medical monitor within 24 hours
of learning of the abnormality to discuss subject 
safety. 

Subject can continue study treatment 

Subject must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until they resolve, stabilise or return to 
within baseline 

If at any time subject meets the liver chemistry 
stopping criteria, proceed as described above

If ALT decreases from ALT 5xULN and <8xULN 
to ≥3xULN but <5xULN, continue to monitor liver 
chemistries weekly. 

If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor subjects twice monthly 
until liver chemistries normalize or return to within 
baseline.


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References
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784.
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P, Gault E.  Quantification 
of Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates 
Different Patterns of Virological Response to Interferon Therapy in Chronically Infected 
Patients.  J Clin Microbiol. 2005;43(5):2363–2369. 


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12.4.
Appendix 4: Genetic Research
Genetic Research Objectives and Analyses
The objectives of the genetic research are to investigate the relationship between genetic 
variants and: 

Response to medicine, including any treatment regimens under investigation in 
this study or any concomitant medicines;

T2DM susceptibility, severity, and progression and related conditions.
Genetic data may be generated while the study is underway or following completion of 
the study.  Genetic evaluations may include focused candidate gene approaches and/or 
examination of a large number of genetic variants throughout the genome (whole genome 
analyses). Genetic analyses will utilize data collected in the study and will be limited to 
understanding the objectives highlighted above.  Analyses may be performed using data 
from multiple clinical studies to investigate these research objectives.
Appropriate descriptive and/or statistical analysis methods will be used. A detailed 
description of any planned analyses will be documented in a Reporting and Analysis Plan 
(RAP) prior to initiation of the analysis. Planned analyses and results of genetic 
investigations will be reported either as part of the clinical RAP and study report, or in a 
separate genetics RAP and report, as appropriate.
Study Population
Any subject who is enrolled in the study can participate in genetic research.  Any subject 
who has received an allogeneic bone marrow transplant must be excluded from the 
genetic research.
Study Assessments and Procedures
A key component of successful genetic research is the collection of samples during 
clinical studies. Collection of samples, even when no a priori hypothesis has been 
identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response.  
A 6 ml blood sample will be taken for Deoxyribonucleic acid (DNA) extraction. A blood 
sample is collected at the baseline visit, after the subject has been randomized and 
provided informed consent for genetic research. Instructions for collection and shipping 
of the genetic sample are described in the laboratory manual. The DNA from the blood 
sample may undergo quality control analyses to confirm the integrity of the sample. If 
there are concerns regarding the quality of the sample, then the sample may be destroyed. 
The blood sample is taken on a single occasion unless a duplicate sample is required due 
to an inability to utilize the original sample.  
The genetic sample is labeled (or “coded”) with the same study specific number used to 
label other samples and data in the study.   This number can be traced or linked back to 


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the subject by the investigator or site staff. Coded samples do not carry personal 
identifiers (such as name or social security number). 
Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study, or GSK may destroy the samples sooner.  GSK or those working 
with GSK (for example, other researchers) will only use samples collected from the study 
for the purpose stated in this protocol and in the informed consent form.  Samples may be 
used as part of the development of a companion diagnostic to support the GSK medicinal 
product.
Subjects can request their sample to be destroyed at any time.
Informed Consent
Subjects who do not wish to participate in the genetic research may still participate in the 
study.  Genetic informed consent must be obtained prior to any blood being taken.
Subject Withdrawal from Study
If a subject who has consented to participate in genetic research withdraws from the 
clinical study for any reason other than being lost to follow-up, the subject will be given a 
choice of one of the following options concerning the genetic sample, if already 
collected:
Continue to participate in the genetic research in which case the genetic DNA sample is 
retained
Discontinue participation in the genetic research and destroy the genetic DNA sample 
If a subject withdraws consent for genetic research or requests sample destruction for any 
reason, the investigator must complete the appropriate documentation to request sample 
destruction within the timeframe specified by GSK and maintain the documentation in 
the site study records. 
Genotype data may be generated during the study or after completion of the study and 
may be analyzed during the study or stored for future analysis. 
If a subject withdraws consent for genetic research and genotype data has not been 
analyzed, it will not be analyzed or used for future research.  
Genetic data that has been analyzed at the time of withdrawn consent will continue to be 
stored and used, as appropriate. 
Screen and Baseline Failures
If a sample for genetic research has been collected and it is determined that the subject 
does not meet the entry criteria for participation in the study, then the investigator should 
instruct the subject that their genetic sample will be destroyed. No forms are required to 
complete this process as it will be completed as part of the consent and sample 


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reconciliation process.  In this instance a sample destruction form will not be available to 
include in the site files.
Provision of Study Results and Confidentiality of Subject’s Genetic Data
GSK may summarize the genetic research results in the clinical study report, or 
separately and may publish the results in scientific journals. 
GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the subject, 
family members, insurers, or employers of individual genotyping results that are not 
known to be relevant to the subject’s medical care at the time of the study, unless 
required by law. This is due to the fact that the information generated from genetic 
studies is generally preliminary in nature, and therefore the significance and scientific 
validity of the results are undetermined.  Further, data generated in a research laboratory 
may not meet regulatory requirements for inclusion in clinical care.


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12.5.
Appendix 5: Definition of and Procedures for Recording, 
Evaluating, Follow-Up and Reporting of Adverse Events
12.5.1.
Definition of Adverse Events
Adverse Event Definition:

An AE is any untoward medical occurrence in a patient or clinical investigation 
subject, temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product.

NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product.
Events meeting AE definition include:

Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECGs, radiological scans, vital signs 
measurements), including those that worsen from baseline, and felt to be clinically 
significant in the medical and scientific judgment of the investigator.

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication (overdose per se will not be reported as an 
AE/SAE unless this is an intentional overdose taken with possible suicidal/self-
harming intent.  This should be reported regardless of sequelae).

"Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE.  However, the signs and symptoms and/or clinical 
sequelae resulting from lack of efficacy will be reported if they fulfill the definition
of an AE or SAE.
Events NOT meeting definition of an AE include:

Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the subject’s condition.

The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the subject’s 


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condition.

Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is an AE.

Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen.
12.5.2.
Definition of Serious Adverse Events
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease, etc).
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, 
at any dose:
a.
Results in death
b.
Is life-threatening
NOTE:
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
subject was at risk of death at the time of the event.  It does not refer to an event, which 
hypothetically might have caused death, if it were more severe.
c.
Requires hospitalization or prolongation of existing hospitalization
NOTE:

In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or out-patient setting.  Complications that occur during hospitalization are 
AEs.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the AE should be considered serious.

Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in disability/incapacity
NOTE:

The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.


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
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (e.g. sprained ankle) which may interfere or prevent everyday 
life functions but do not constitute a substantial disruption
e.
Is a congenital anomaly/birth defect
f.
Other situations:

Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize 
the subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition.  These should also be considered 
serious.

Examples of such events are invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse
g.
Is associated with liver injury and impaired liver function defined as:

ALT 3xULN and total bilirubin* 2xULN (>35% direct), or

ALT 3xULN and INR** > 1.5.
* Serum bilirubin fractionation should be performed if testing is available; if unavailable, 
measure urinary bilirubin via dipstick.  If fractionation is unavailable and ALT 3xULN 
and total bilirubin 2xULN, then the event is still to be reported as an SAE.
** INR testing not required per protocol and the threshold value does not apply to 
subjects receiving anticoagulants.  If INR measurement is obtained, the value is to be 
recorded on the SAE form.
12.5.3.
Definition of Cardiovascular Events
Cardiovascular Events (CV) Definition:
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs:

Myocardial infarction/unstable angina

Congestive heart failure

Arrhythmias

Valvulopathy

Pulmonary hypertension


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
Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularization
12.5.4.
Recording of AEs and SAEs
AEs and SAE Recording:

When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
relative to the event.

The investigator will then record all relevant information regarding an AE/SAE in 
the eCRF

It is not acceptable for the investigator to send photocopies of the subject’s medical 
records to GSK in lieu of completion of the GSK, AE/SAE eCRF page.

There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records prior to 
submission of to GSK.

The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis will be 
documented as the AE/SAE and not the individual signs/symptoms.
12.5.5.
Evaluating AEs and SAEs
Assessment of Intensity
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and will assign it to one of the following categories:

Mild:  An event that is easily tolerated by the subject, causing minimal discomfort 
and not interfering with everyday activities.

Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities

Severe:  An event that prevents normal everyday activities. - an AE that is assessed 
as severe will not be confused with an SAE. Severity is a category utilized for rating 
the intensity of an event; and both AEs and SAEs can be assessed as severe.

An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.


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Assessment of Causality

The investigator is obligated to assess the relationship between study treatment and 
the occurrence of each AE/SAE.

A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled 
out.

The investigator will use clinical judgment to determine the relationship.

Alternative causes, such as natural history of the underlying diseases, concomitant 
therapy, other risk factors, and the temporal relationship of the event to the study 
treatment will be considered and investigated.

The investigator will also consult the Investigator Brochure (IB) and/or Product 
Information, for marketed products, in the determination of his/her assessment.

For each AE/SAE the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality.

There may be situations when an SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK.  However, it is very important 
that the investigator always make an assessment of causality for every event 
prior to the initial transmission of the SAE data to GSK.

The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.

The causality assessment is one of the criteria used when determining regulatory 
reporting requirements.
Follow-up of AEs and SAEs

The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to 
elucidate as fully as possible the nature and/or causality of the AE or SAE.

The investigator is obligated to assist.  This may include additional laboratory tests 
or investigations, histopathological examinations or consultation with other health 
care professionals.

If a subject dies during participation in the study or during a recognized follow-up 
period, the investigator will provide GSK with a copy of any post-mortem findings, 
including histopathology.

New or updated information will be recorded in the originally completed eCRF.

The investigator will submit any updated SAE data to GSK within the designated 
reporting time frames.


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12.5.6.
Reporting of SAEs to GSK
SAE reporting to GSK via electronic data collection tool

Primary mechanism for reporting SAEs to GSK will be the electronic data collection 
tool

If the electronic system is unavailable for greater than 24 hours, the site will use the 
paper SAE data collection tool and fax it to the Medical Monitor or the SAE 
coordinator

Site will enter the serious adverse event data into the electronic system as soon as it 
becomes available.

After the study is completed at a given site, the electronic data collection tool (e.g., 
InForm system) will be taken off-line to prevent the entry of new data or changes to 
existing data

If a site receives a report of a new SAE from a study subject or receives updated data 
on a previously reported SAE after the electronic data collection tool has been taken 
off-line, the site can report this information on a paper SAE form or to the Medical 
Monitor or the SAE coordinator by telephone.

Contacts for SAE receipt can be found at the beginning of this protocol on the 
Sponsor/Medical Monitor Contact Information page.


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12.6.
Appendix 6: Collection of Pregnancy Information
Pregnancy information on female study subjects 

Investigator will collect pregnancy information on any female subject, who becomes 
pregnant while participating in this study

Information will be recorded on the appropriate form and submitted to GSK within 2 
weeks of learning of a subject's pregnancy.

Subject will be followed to determine the outcome of the pregnancy. The investigator 
will collect follow up information on mother and infant, which will be forwarded to 
GSK.  Generally, follow-up will not be required for longer than 6 to 8 weeks beyond 
the estimated delivery date. 

Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.

While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.

A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  

Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator will be reported to GSK 
as described in Appendix 5. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting.
Any female subject who becomes pregnant while participating 

Will discontinue study medication.


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12.7.
Appendix 7: Immunogenicity Testing Algorithm
The immunogenicity of albiglutide will be evaluated using the following testing schemes 
and assays.
Sample Testing Schemes
Samples for immunogenicity testing will be obtained as detailed in the time and events 
schedule (Section 7.1) and Section 7.7.
The presence of anti-albiglutide antibodies will be assessed using a validated screening 
enzyme-linked immunosorbent assay (ELISA).  If serum samples contain anti-albiglutide 
antibodies, they will be further analyzed in a confirmation assay to show specificity for 
albiglutide.  Confirmed positive samples will be titrated to obtain the anti-albiglutide titer 
value.  To test whether anti-albiglutide antibodies cross-react with endogenous glucagon-
like peptide (GLP-1) or human albumin (HA), positive samples will be tested in 
secondary assays which include anti-GLP-1or anti-HA screening ELISA’s, respectively.  
In addition, anti-albiglutide positive samples will be tested for neutralizing activity 
against the drug in a cell-based assay.  Subjects that are positive for anti-albiglutide 
neutralizing antibodies and anti-GLP-1 antibodies may be assessed in an anti-GLP-1 
neutralizing antibody assay for neutralizing activity against GLP-1.
Antibody Detection Assays
The detection assays are ELISA- based and utilize a tiered testing approach.  The anti-
albiglutide assay includes screening, confirmation and titration assays. The anti-GLP-1 
ELISA includes screening and confirmation steps.  For the anti-HA ELISA only a 
screening step is feasible.
The procedure for the albiglutide immunoglobulin (IgG/A/M) ELISA is described below:
1.
96-well ELISA plates are coated with albiglutide overnight.
2. Samples are diluted 1:50 and incubated on blocked plates for 3 hours.
3. A horseradish peroxidase (HRP)-labeled anti-human IgG/A/M antibody is used as 
the detection antibody.
4. A tetramethylbenzidine peroxidase substrate is used to produce the enzymatic 
reaction which is followed by an acid stop procedure. 
5. The plates are read at 450 nm using a SpectraMax Plus 384 reader (Molecular 
Devices LLC, Sunnyvale, California), or the equivalent.
6. A positive control (normal human serum pool spiked with anti-human GLP-1 
antibody) and negative control (pooled normal human serum) are included on 
each assay plate.
7. Relative optical density values are calculated by dividing the mean optical density 
of sample or positive control by the mean optical density of the negative control.


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Screening
Screening comprises determination of a cutoff value for drug-naïve T2DM subjects and 
identification of serum samples potentially positive for anti-albiglutide antibody.
Confirmation
Specificity of serum antibodies is confirmed by competing their binding to albiglutide 
immobilized on plates with excess albiglutide in solution.  If the sample is still positive 
after the confirmation assay, the sample will be reported as positive and further analysis 
will be done by the titration and neutralizing antibody assay and other secondary assays.
Titration
Confirmed positive samples will be titrated to obtain a titer  value of anti-albiglutide 
antibody.
Neutralizing Antibody Assays
The neutralizing antibody assays are cell-based reporter gene assays, which include 
screening, confirmation and titration assays.  Albiglutide-neutralizing activity is 
measured by adding serum samples pre-incubated with a fixed concentration of 
albiglutide to GLP-1 receptor/CRE (cyclic adenosine monophosphate response element)-
luciferase transfected cells and measuring luminescence intensity after 3 hours of 
incubation.  Samples possessing neutralizing activity will generate a reduced signal and 
will be further tested in confirmation (specificity) assay if the generated signal is positive 
(i.e., below the assay’s screening cutoff).  Confirmed positive samples will be titrated to 
obtain a titer value of neutralizing anti-albiglutide antibody.
Immunogenicity Testing Report
The immunogenicity testing report will include the incidence of immunogenicity, 
incidence of neutralizing antibodies and the antibody titers (binding and neutralization to 
albiglutide).  Cross-reactive antibodies to GLP-1 and HA will be discussed.


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12.8.
Appendix 8: Country Specific Requirements
No country-specific requirements exist.


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12.9.
Appendix 9: Protocol Amendment Changes
Changes Resulting from Protocol Amendment 1
This amendment is applicable to all participating countries.
Summary of Changes
1. Benefit risk table modified to provide further details relating to mitigation 
strategies.
2. Exclusion criteria related to abnormal TSH modified.
3. Exclusion criteria numbering corrected. Exclusion criteria for ‘fasting triglyceride 
level >750 mg/dL at screening’ was un-numbered and formed part of exclusion 
criteria 14. 
4. Exclusion criteria relating to positive urine drug screen result at Screening 
modified.
5. New text to clarify visit windows.
6. Time and Event Table modified to add HbA1c sample at Week 12
7. Time and Event Table modified to remove the Week 13 PK sample and add a PK 
sample at Week 12.
8. Details for collection of PK samples moved to SPM.
9. Timings for handling of missing data changed.


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List of Specific Changes
Amendment 1:
Section 4.6.1, Table 2, Risk Assessment for Albiglutide
Original text:
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Pancreatitis
Acute pancreatitis has been reported in association with albiglutide and other 
GLP-1 receptor agonists in clinical trials and during postmarketing experience.
Albiglutide has not been studied in subjects with a history of pancreatitis to 
determine whether they are at increased risk for pancreatitis.
Subjects with a history of acute or chronic pancreatitis are 
excluded from entering the study (See Section 5.2).
Subjects will be informed of the characteristic symptom of 
pancreatitis: persistent severe abdominal pain. If 
pancreatitis is suspected, albiglutide should be promptly 
discontinued and if pancreatitis is confirmed, study 
treatment will not be restarted (see Section 5.5).
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Gastrointestinal (GI) events.
Albiglutide has not been studied in subjects with severe GI disease, including 
severe gastroparesis. 
Use of albiglutide can be associated with GI side effects such as diarrhea, 
nausea, and vomiting.
Subjects with severe gastroparesis are excluded from 
entering the study (See Section 5.2).
Subjects with a history of significant GI surgery that in the 
opinion of the investigator is likely to significantly affect 
upper GI or pancreatic function  are excluded from 
entering the study (See Section 5.2).
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Hypoglycemia.
Albiglutide’s mechanism of action is associated with a low intrinsic risk of 
significant hypoglycemia when used as monotherapy or in combination with 
agents such as metformin which also have low intrinsic risk for significant 
All subjects are required to have a last indicator of 
glycemic control of above HbA1c = 7% which is 
expected to reduce the risk of hypoglycemia when 


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hypoglycemia. 
starting albiglutide. 
Subjects are neither allowed to use insulin nor insulin 
secretagogues during the study. Except as part of 
hyperglycemia rescue (see Section 5.4)
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Immunogenicity 
(e.g., including anti-drug antibodies, 
clinical sequelae of antidrug 
antibodies, severe hypersensitivity 
reactions, and other potential 
immune-related AEs).
Hypersensitivity reactions are of potential concern with any injected 
protein and were reported rarely in the Phase III program with lyophilized 
albiglutide. In the Phase III program one subject (anti-albiglutide antibody 
negative) developed rash and itching; and upon rechallenge recurrence of 
these symptoms associated with dyspnea. 
Risk assessment of the albiglutide molecule predicted low immunogenic 
potential, which was substantiated for the commercial lyophilized DCC pen 
injector product in the registration program. Treatment-emergent anti-drug 
antibodies were detected in ~5% subjects over studies of up to 3 years duration 
and were generally transient, of low titer, and not neutralizing.
Subjects who tested positive for anti-albiglutide antibodies experienced a similar 
glycemic response (HbA1c and fasting plasma glucose) to those who did not 
test positive for antibodies. Other than injection site reactions (see below), the 
overall safety profile appeared similar among the subset of subjects who did 
and those who did not test positive for anti-albiglutide antibodies. 
Changes in the propensity of the liquid product to form aggregates could have 
an impact on anti-drug antibody characteristics or immune related AEs.  
However, the likelihood of clinically important changes in anti-drug antibody 
characteristics or immune related AEs with the liquid albiglutide drug product 
compared to the lyophilized drug product is considered low based on the 
absence of substantive qualitative differences between formulations.
A pre-exposure baseline serum sample will be taken and 
tested for pre-existing ADAs.
The development of anti-albiglutide antibodies will be 
assessed as part of this study.
Injection site reactions (ISRs)
Albiglutide injections may cause rash, erythema or itching and/or other reactions 
at the site of injection. 
In the Phase III program with the lyophilized drug product, most subjects with 
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via guidance for investigators (see 


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ISRs did not test positive for anti-albiglutide antibodies. However, injection site 
reactions were reported more frequently among those who did test positive for 
anti-albiglutide antibodies (41% of the ADA positive subjects reported one or 
more injection site reactions) than among those who were consistently antibody 
negative (14% of the antidrug antibody negative subjects reported one or more 
injection site reactions).  
Overall, for albiglutide, injection site reactions have not been associated with 
clinically significant sequelae; although they can be a tolerability issue and were 
the most common reason for withdrawal of study medication for subjects 
(approximately 2.0%) in the albiglutide group.
Differences between formulation characteristics (e.g. lower pH and larger 
volume for the 50 mg dose of the liquid formulation) may impact the injection 
site reaction profile.
Section 6 of the IB) and informed consent form for 
subjects.
Other adverse reactions
(e.g., pneumonia, atrial 
fibrillation/atrial flutter, appendicitis, 
and hypersensitivity reactions)
In the Phase III program in T2DM, other possible albiglutide related adverse 
reactions were identified. These events occurred at a cumulative incidence <3% 
in studies up to 3 years in duration. These events were reported more frequently 
with albiglutide than comparators. 
Subjects with a known allergy to albiglutide or any 
product components (including yeast and human 
albumin) are excluded from the study (See Section 
5.2).  
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.  
Thyroid C-cell tumors
GLP-1 receptor agonists, including albiglutide increase serum calcitonin in 
rodents and other GLP-1 receptor agonists are associated with thyroid C-cell 
focal hyperplasia and C-cell tumors in rodents  It is unknown whether GLP-1 
receptor agonists are associated with thyroid C-cell tumors in humans, including 
medullary thyroid cancer (MTC). 
Subjects with a personal or family history of MTC or 
subjects with Multiple Endocrine Neoplasia syndrome type 
2 (MEN-2) are excluded from the study (See Section 5.2).
Subjects with treatment emergent thyroid nodules should 
be referred to a specialist for evaluation in accordance with 
local treatment guidelines.  Routine monitoring of serum 
calcitonin is not recommended.  However, if serum 
calcitonin is found to be elevated the subject should be 
referred to a specialist for further evaluation. If MTC or 
other thyroid C-cell neoplasia is diagnosed, study 
treatment will be discontinued (see Section 5.5).


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Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Other malignant neoplasms
Theoretical concerns have been raised regarding use of incretin based 
therapies and other malignancies such as pancreatic cancer [Egan, 2014] and 
malignancy when used in combination with insulin based on hypotheses of 
biological plausibility [European Public Assessment Report, 2014], and 
hematological malignancies [FDA Summary Basis of Approval, 2014].
Subjects with a history of cancer that has not been in full 
remission for at least 3 years before screening are 
excluded from the study (See Section 5.2).
Risk communication via guidance for investigators 
(see Section 6 of the IB) and informed consent form for 
subjects.  
Cardiovascular (CV) safety of 
antidiabetic therapy
T2DM is associated with an elevated risk of CV disease. Global regulatory 
agencies require new antidiabetic therapies to demonstrate that the new 
therapy is not associated with an unacceptable increase in CV risk. 
In the Phase III registration program, an independent Clinical Endpoint 
Committee prospectively adjudicated blinded CV events. The final CV meta-
analysis showed no increased CV risk (MACE [major adverse cardiovascular 
event] + composed of CV death, myocardial infarction [MI], stroke, and 
hospitalization for unstable angina) with albiglutide versus all comparators 
(MACE+ hazard ratio = 1.00; 95% CI: 0.68, 1.49).
Subjects with clinically significant CV and/or 
cerebrovascular disease within 3 months before screening
will be excluded from the study. Further details are 
provided in Section 5.2
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.  
Hepatotoxicity
Hepatotoxicity is an area of interest in drug development.  Patients with T2DM 
are at increased risk for liver enzyme abnormalities and disease related liver 
conditions.  One subject treated with albiglutide in the Phase III clinical program 
developed probable drug induced liver injury with an asymptomatic elevation in 
alanine amino transferase (ALT) and total bilirubin although the cases had some 
atypical features and complicating factors . 
Routine liver safety laboratory evaluations will be 
conducted and specific withdrawal criteria for elevated liver 
function tests have been defined (See Section 5.5.1).
Subject population with severe renal 
impairment (estimated glomerular 
filtration rate (eGFR) 
<30 mL/min/1.73m2)
Experience in T2DM subjects with severe renal impairment is limited (in the 
Phase III programme a total of 19 subjects with eGFR <30 mL/min/1.73m2
received albiglutide). 
In a Phase III study of patients with varying degrees of renal impairment, in the 
albiglutide group, on-therapy GI AEs occurred with a higher incidence and 
higher event rate in subjects with moderate and severe renal impairment 
compared to those with mild renal impairment. GI events may lead to 
dehydration and worsen renal function. 
Subjects with an eGFR ≤30 mL/min/1.73 m2 (calculated 
using the Modification of Diet in Renal Disease (MDRD) 
formula) are excluded from the study (see Section 5.2).
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.  


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Summary of Data/Rationale for Risk
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Drug interactions
Albiglutide causes a delay in gastric emptying, and thereby has the potential to 
impact the absorption of concomitantly administered oral medications.
During the development program, drug interactions studies were conducted 
with digoxin, warfarin, oral contraceptives, and simvastatin which demonstrated 
no clinically relevant PK or PD effects. 
Investigators will be advised to take the effect of albiglutide 
on gastric emptying into account when prescribing 
concomitant medication.
Fetal & neonatal developmental 
toxicity
Studies in animals have shown reproductive toxicity. The potential risk for 
humans is unknown.  Albiglutide administration during the major period of 
organogenesis in female mice resulted in embryofetal lethality, and bent/wavy 
ribs in the fetus at 50 mg/kg/day.  
Given that albiglutide is an albumin-based protein therapeutic, it is likely to be 
transferred to breast milk and may increase neonatal –cell mass.  
Decreased body weight in offspring was observed in mice treated with 
albiglutide during gestation and lactation.
Subjects who are breastfeeding, pregnant or planning a 
pregnancy during the course of the study are excluded. 
Additionally, all females of child-bearing potential must be 
taking adequate contraception during the study and have a 
negative pregnancy test prior to entry. See Section 5.1 for 
further details.
Accelerated sexual maturation in 
juveniles
Long-acting GLP-1R agonists have the potential to accelerate sexual maturation 
in monkeys based on absolute testes weight and similar trends in prostate, 
seminal vesicle, epididymides weights and histological assessment of maturity.
Subjects under 18 years of age are excluded (see Section 
5.1).
Albiglutide matching placebo 
injections
Albiglutide placebo injections using the lyophilized DCC pen injector were 
associated with a clinically relevant rate of injection site reactions in the Phase 
III studies.
There is no experience with placebo injections using the liquid auto-injector, 
including volume and pH differences from the lyophilized product placebo.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via informed consent form for 
subjects.
Amended text:
Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Pancreatitis
Acute pancreatitis has been reported in association with albiglutide and other 
GLP-1 receptor agonists in clinical trials and during postmarketing experience.
Albiglutide has not been studied in subjects with a history of pancreatitis to 
Subjects with a history of acute or chronic pancreatitis are 
excluded from entering the study (See Section 5.2).
Subjects will be informed of the characteristic symptom of 


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determine whether they are at increased risk for pancreatitis.
pancreatitis: persistent severe abdominal pain. If 
pancreatitis is suspected, albiglutide should be promptly 
discontinued and if pancreatitis is confirmed, study 
treatment will not be restarted (see Section 5.5).
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Gastrointestinal (GI) events.
Albiglutide has not been studied in subjects with severe GI disease, including 
severe gastroparesis. 
Use of albiglutide can be associated with GI side effects such as diarrhea,
nausea, and vomiting.
Subjects with severe gastroparesis are excluded from 
entering the study (See Section 5.2).
Subjects with a history of significant GI surgery that in the 
opinion of the investigator is likely to significantly affect 
upper GI or pancreatic function  are excluded from 
entering the study (See Section 5.2).
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Hypoglycemia.
Albiglutide’s mechanism of action is associated with a low intrinsic risk of 
significant hypoglycemia when used as monotherapy or in combination with 
agents such as metformin which also have low intrinsic risk for significant 
hypoglycemia. 
To reduce the risk of hypoglycemia when starting 
albiglutide all subjects are required to have HbA1c 
≥7.0 at screening (see Section 5.1). 
Subjects are neither allowed to use insulin nor insulin 
secretagogues during the study. Except as part of 
hyperglycemia rescue (see Section 5.4)
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Immunogenicity 
(e.g., including anti-drug antibodies, 
clinical sequelae of antidrug 
antibodies, severe hypersensitivity 
reactions, and other potential 
Risk assessment of the albiglutide molecule predicted low immunogenic 
potential, which was substantiated for the commercial lyophilized DCC pen 
injector product in the registration program. Treatment-emergent anti-drug 
antibodies were detected in ~5% subjects over studies of up to 3 years duration 
and were generally transient, of low titer, and not neutralizing.
A pre-exposure baseline serum sample will be taken and 
tested for pre-existing ADAs.
The development of anti-albiglutide antibodies will be 
assessed as part of this study.


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Potential Risk of Clinical 
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Summary of Data/Rationale for Risk
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immune-related AEs).
Subjects who tested positive for anti-albiglutide antibodies experienced a similar 
glycemic response (HbA1c and fasting plasma glucose) to those who did not 
test positive for antibodies. Other than injection site reactions (see below), the 
overall safety profile appeared similar among the subset of subjects who did 
and those who did not test positive for anti-albiglutide antibodies. 
Changes in the propensity of the liquid product to form aggregates could have 
an impact on anti-drug antibody characteristics or immune related AEs.  
However, the likelihood of clinically important changes in anti-drug antibody 
characteristics or immune related AEs with the liquid albiglutide drug product 
compared to the lyophilized drug product is considered low based on the 
absence of substantive qualitative differences between formulations.
Hypersensitivity Reactions
Systemic allergic/hypersensitivity reactions are of potential concern with 
any injected protein and were reported rarely in the Phase III program with 
lyophilized albiglutide. Data have not demonstrated an association of 
albiglutide with an increased incidence of anaphylaxis, angioedema, or 
urticaria. However, there was one non-serious hypersensitivity event (rash 
and itching associated with dyspnea upon rechallenge) that was 
consistent with a possible albiglutide-related systemic hypersensitivity 
reaction in a female subject who was anti-albiglutide antibody negative. 
See Section 5.4 of the IB.
Subjects with a known allergy to albiglutide or any
product components (including yeast and human 
albumin) are excluded from the study (See Section 
5.2).  
Subjects will be informed of the symptoms of severe 
hypersensitivity or allergy and be advised to seek 
medical assistance immediately. 
Risk communication via guidance for investigators 
(see Section 6 of the IB) and informed consent form for 
subjects.
Injection site reactions (ISRs)
Albiglutide injections may cause rash, erythema or itching and/or other reactions 
at the site of injection. 
In the Phase III program with the lyophilized drug product, most subjects with 
ISRs did not test positive for anti-albiglutide antibodies. However, injection site 
reactions were reported more frequently among those who did test positive for 
anti-albiglutide antibodies (41% of the ADA positive subjects reported one or 
more injection site reactions) than among those who were consistently antibody 
negative (14% of the antidrug antibody negative subjects reported one or more 
injection site reactions).  
Overall, for albiglutide, injection site reactions have not been associated with 
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
The development of injection site reactions will be 
assessed as part of this study.


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clinically significant sequelae; although they can be a tolerability issue and were 
the most common reason for withdrawal of study medication for subjects 
(approximately 2.0%) in the albiglutide group.
Differences between formulation characteristics (e.g. lower pH and larger 
volume for the 50 mg dose of the liquid formulation) may impact the injection 
site reaction profile.
Other adverse reactions
(e.g., pneumonia, atrial 
fibrillation/atrial flutter, appendicitis)
In the Phase III program in T2DM, other possible albiglutide related adverse 
reactions were identified. These events occurred at a cumulative incidence <3% 
in studies up to 3 years in duration. These events were reported more frequently 
with albiglutide than comparators. 
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.  
Thyroid C-cell tumors
GLP-1 receptor agonists, including albiglutide increase serum calcitonin in 
rodents and other GLP-1 receptor agonists are associated with thyroid C-cell 
focal hyperplasia and C-cell tumors in rodents  It is unknown whether GLP-1 
receptor agonists are associated with thyroid C-cell tumors in humans, including 
medullary thyroid cancer (MTC). 
Subjects with a personal or family history of MTC or 
subjects with Multiple Endocrine Neoplasia syndrome type 
2 (MEN-2) are excluded from the study (See Section 5.2).
Subjects with treatment emergent thyroid nodules should 
be referred to a specialist for evaluation in accordance with 
local treatment guidelines.  Routine monitoring of serum 
calcitonin is not recommended.  However, if serum 
calcitonin is found to be elevated the subject should be 
referred to a specialist for further evaluation. If MTC or 
other thyroid C-cell neoplasia is diagnosed, study 
treatment will be discontinued (see Section 5.5).
Other malignant neoplasms
Theoretical concerns have been raised regarding use of incretin based 
therapies and other malignancies such as pancreatic cancer [Egan, 2014] and 
malignancy when used in combination with insulin based on hypotheses of 
biological plausibility [European Public Assessment Report, 2014], and 
hematological malignancies [FDA Summary Basis of Approval, 2014].
Relevant data on pancreatic cancer are summarized in 
IB Section 5.4.
Subjects with a history of cancer that has not been in full 
remission for at least 3 years before screening are 
excluded from the study (See Section 5.2).
Cardiovascular (CV) safety of 
antidiabetic therapy
T2DM is associated with an elevated risk of CV disease. Global regulatory 
agencies require new antidiabetic therapies to demonstrate that the new 
therapy is not associated with an unacceptable increase in CV risk. 
In the Phase III registration program, an independent Clinical Endpoint 
Committee prospectively adjudicated blinded CV events. The final CV meta-
Relevant data on cardiovascular events are 
summarized in IB Section 5.4.
Subjects with clinically significant CV and/or 
cerebrovascular disease within 3 months before screening 
will be excluded from the study. Further details are 


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analysis showed no increased CV risk (MACE [major adverse cardiovascular 
event] + composed of CV death, myocardial infarction [MI], stroke, and 
hospitalization for unstable angina) with albiglutide versus all comparators 
(MACE+ hazard ratio = 1.00; 95% CI: 0.68, 1.49). See Section 5.4 of the IB.
provided in Section 5.2
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects. 
Hepatotoxicity
Hepatotoxicity is an area of interest in drug development.  Patients with T2DM 
are at increased risk for liver enzyme abnormalities and disease related liver 
conditions.  One subject treated with albiglutide in the Phase III clinical program 
developed probable drug induced liver injury with an asymptomatic elevation in 
alanine amino transferase (ALT) and total bilirubin although the cases had some 
atypical features and complicating factors . 
Routine liver safety laboratory evaluations will be 
conducted and specific withdrawal criteria for elevated liver 
function tests have been defined (See Section 5.5.1).
Subject population with severe renal 
impairment (estimated glomerular 
filtration rate (eGFR) 
<30 mL/min/1.73m2)
Experience in T2DM subjects with severe renal impairment is limited (in the 
Phase III programme a total of 19 subjects with eGFR <30 mL/min/1.73m2
received albiglutide). 
In a Phase III study of patients with varying degrees of renal impairment, in the 
albiglutide group, on-therapy GI AEs occurred with a higher incidence and 
higher event rate in subjects with moderate and severe renal impairment 
compared to those with mild renal impairment. GI events may lead to 
dehydration and worsen renal function. 
Subjects with an eGFR ≤30 mL/min/1.73 m2 (calculated 
using the Modification of Diet in Renal Disease (MDRD) 
formula) are excluded from the study (see Section 5.2).
Risk communication via guidance for investigators (see 
Section 5.4 and Section 6 of the IB) and informed consent 
form for subjects.  
Drug interactions
Albiglutide causes a delay in gastric emptying, and thereby has the potential to 
impact the absorption of concomitantly administered oral medications.
During the development program, drug interactions studies were conducted 
with digoxin, warfarin, oral contraceptives, and simvastatin which demonstrated 
no clinically relevant PK or PD effects. 
Investigators will be advised to take the effect of albiglutide 
on gastric emptying into account when prescribing 
concomitant medication.
Fetal & neonatal developmental 
toxicity
Studies in animals have shown reproductive toxicity. The potential risk for 
humans is unknown.  Albiglutide administration during the major period of 
organogenesis in female mice resulted in embryofetal lethality, and bent/wavy 
ribs in the fetus at 50 mg/kg/day.  Offspring of mice dosed with 50 mg/kg/day 
during organogenesis had reduced pre-weaning body weight (which 
recovered after weaning), dehydration and coldness, and a delay in 
balanopreputial separation.
Subjects who are breastfeeding, pregnant or planning a 
pregnancy during the course of the study are excluded. 
Additionally, all females of child-bearing potential must be 
taking adequate contraception during the study and have a 
negative pregnancy test prior to entry.  See Section 5.1 for 
further details.


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Potential Risk of Clinical 
Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Given that albiglutide is an albumin-based protein therapeutic, it is likely to be 
transferred to breast milk. Decreased body weight in offspring was observed in 
mice treated with albiglutide during gestation and lactation.
Accelerated sexual maturation in 
juveniles
Long-acting GLP-1R agonists have the potential to accelerate sexual maturation 
in monkeys based on absolute testes weight and similar trends in prostate, 
seminal vesicle, epididymides weights and histological assessment of maturity.
Subjects under 18 years of age are excluded (see Section 
5.1).
Albiglutide matching placebo 
injections
Albiglutide placebo injections using the lyophilized DCC pen injector were 
associated with a clinically relevant rate of injection site reactions in the Phase 
III studies.
There is no experience with placebo injections using the liquid auto-injector, 
including volume and pH differences from the lyophilized product placebo.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via informed consent form for 
subjects.


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Section 5.2, Exclusion Criteria 5
Original text:
5. History of thyroid dysfunction or an abnormal (i.e., outside the normal reference 
range) thyroid function test assessed by thyroid stimulating hormone at screening.
Amended text:
5. Abnormal (i.e., outside the normal reference range) thyroid stimulating hormone 
(TSH) at screening.
Section 5.2, Exclusion Criteria 14, last sentence.
Original text:
14. eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula) at screening.
Note: As the use of metformin in subjects with varying degrees of renal function 
may differ from country to country, use of metformin should be in accordance 
with the metformin product label within the participating country.
Fasting triglyceride level >750 mg/dL at screening.
Amended text:
14. eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula) at screening.
Note: As the use of metformin in subjects with varying degrees of renal function 
may differ from country to country, use of metformin should be in accordance 
with the metformin product label within the participating country.
Etc……
24. Fasting triglyceride level >750 mg/dL at screening.
Section 5.2, Exclusion Criteria 21
Original text:
21. A positive pre-study drug/alcohol screen.  
New text:
21. Positive urine alcohol/drug screen result at Screening, unless the subject is 
taking a medically approved medication for which a positive drug screen simply 
verifies the use of this medication
Section 5.2, Section 7, paragraph 4 and paragraph 5
New text:


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Study visits between Baseline (Week 0) and End of treatment (Week 26) will have a visit 
window of ±3 days and the follow-up visit (Week 34) will have a visit window of ±7 
days. If extraordinary events that make it impossible for subjects to complete a 
visit/dosing within the visit window (e.g., holidays, personal emergencies), the 
investigator should contact the medical monitor for advice.  
If a subject misses a weekly scheduled visit for receiving albiglutide treatments, the 
albiglutide treatments should be administered as soon as possible within 3 days after the 
missed dose. Thereafter, subjects can resume dosing on their usual day of administration. 
If it is more than 3 days after the missed dose, the site staff should wait and administer at 
the subject’s next regularly scheduled visit.  If a subject misses 2 or more consecutive 
dosing, the investigator should contact the medical monitor to discuss options for helping 
assure better adherence.  The medical monitor shall make a decision (on a case by case 
basis) on whether the subject should be withdrawn from the study.


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Section 7.1, Time and Events Table HbA1c
Original text:
Procedure
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Week
-2
0
1
2
3
4
5
6
7
8
9
10
11
12
HbA1c 6,9
X
X
X
X
X
Amended text:
Procedure
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Week
-2
0
1
2
3
4
5
6
7
8
9
10
11
12
HbA1c 6,9
X
X
X
X
X
X
Section 7.1, Time and Events Table PK Sampling
Original text:
Procedure
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Week
-2
0
1
2
3
4
5
6
7
8
9
10
11
12
PK samples10


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Procedure
Treatment
End of 
Treatment
13,14
Follow-
up15
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
PK samples10
X
X
Amended text:
Procedure
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Week
-2
0
1
2
3
4
5
6
7
8
9
10
11
12
PK samples10
X
Procedure
Treatment
End of 
Treatment
13,14
Follow-
up15
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
PK samples10
X


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Section 7.6.1, Blood Sample Collection
Original text:
Approximately 2 mL of blood will be collected into 3mL di-potassium 
ethylenediaminetetraacetic acid (K2-EDTA) tubes. The sample will be centrifuged in a 
refrigerated (4°C) centrifuge at 1500 x g for 15 minutes. The resulting plasma will be 
transferred into an appropriately labeled 1.8 or 2 mL polypropylene cryovial for 
albiglutide analysis.  The tube must be frozen at -80°C within 60 minutes of collection.  
Amended text:
Blood samples will be collected and stored as detailed in the Study Reference Manual 
(SRM).
Section 12.9.1.1, Handling of Missing Data, Examination of Missing Data Patterns
Original text:
Examination of Missing Data Patterns
It is expected that the pattern of missing data will be similar in both treatment arms given 
that each treatment arm is using the same drug but different formula. 
To examine the nature of missing data, cohorts of subjects will be defined based on the 
scheduled assessments (HbA1c change from baseline) that were completed at Weeks 1, 5, 
9, 13, 17, 21, and 26.

Subjects who have week 1 assessment only

Subjects who have assessments up to and including Week 5 only

Subjects who have assessments up to and including Week 9 only

Subjects who have assessments up to and including Week 13 only

Subjects who have assessments up to and including Week 17 only

Subjects who have assessments up to and including Week 21 only

Subjects who have assessments up to and including Week 26.
The number and percentage of subjects on each treatment in the 7 cohorts defined here 
will be tabulated. Graphical methods will be used to examine changes from baseline over 
time to assess the pattern of outcomes prior to withdrawal.


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Amended text:
Examination of Missing Data Patterns
It is expected that the pattern of missing data will be similar in both treatment arms given 
that each treatment arm is using the same drug but different formula. 
To examine the nature of missing data, cohorts of subjects will be defined based on the 
scheduled assessments (HbA1c change from baseline) that were completed at Weeks 1, 4, 
8, 12, 16, 20, and 26.

Subjects who have week 1 assessment only

Subjects who have assessments up to and including Week 4 only

Subjects who have assessments up to and including Week 8 only

Subjects who have assessments up to and including Week 12 only

Subjects who have assessments up to and including Week 16 only

Subjects who have assessments up to and including Week 20 only

Subjects who have assessments up to and including Week 26.
The number and percentage of subjects on each treatment in the 7 cohorts defined here 
will be tabulated. Graphical methods will be used to examine changes from baseline over 
time to assess the pattern of outcomes prior to withdrawal.


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Changes Resulting from Protocol Amendment 2
This amendment is applicable to all participating countries.
Summary of Changes
1. Protocol modified to allow subjects who discontinue investigational product to be 
followed for safety and efficacy unless the subject is “lost to follow-up” or 
withdraws consent. 
2. Minor updates to benefit risk table 
3. Clarification in inclusion criteria that those subjects on a stable dose of metforim 
must be receiving metformin as monotherapy.
4. Exclusion criteria relating to use of dipeptidyl peptidase-IV inhibitors updated to 
include GLP 1 receptor agonists and other antidiabetic medications.
5. Clarification of metformin dose adjustment.
6. Text relating to prohibited medications modified to provide details on dipeptidyl 
peptidase-IV inhibitors, GLP 1 receptor agonists and other antidiabetic 
medications.
7. Addition of visit windows to Time and Events Table.
8. Footnotes to Time and Events Table updated
9. Modifications made to the primary analysis, secondary analyses, supportive 
primary analyses, impact of missing data on primary analysis, and sensitivity 
analysis.
10. Minor typographical errors


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Synopsis, analysis, primary analysis
Original text
HbA1c change from baseline at Week 26 will be analyzed using a mixed-effect model 
with repeated measures (MMRM) in the intent-to-treat (ITT) population. MMRM will 
use all available data (including post-hyperglycemia rescue data). Non-inferiority testing 
will be performed at a one-sided alpha of 0.025 and non-inferiority margin of 0.4.
Amended text:
HbA1c change from baseline at Week 26 will be analyzed using a mixed-effect model 
with repeated measures (MMRM) in the intent-to-treat (ITT) population.  MMRM will 
use all available data, including post-hyperglycemia rescue data, and will include data 
from subjects who discontinue treatment.  Imputation under the non-inferiority null 
hypothesis for missing data will be incorporated. Non-inferiority testing will be 
performed at a one-sided alpha of 0.025 and non-inferiority margin of 0.4.
Synopsis, analysis, secondary analyses, third paragraph
Original text
The secondary endpoint FPG change from baseline will be analyzed analogous to the 
primary endpoint HbA1c using MMRM. Imputation for missing data will not be 
incorporated for the secondary endpoint FPG.
Amended text:
The secondary endpoint FPG change from baseline at Week 26 will be analyzed using 
MMRM without imputation. 
Section 4.1, Figure 1, study schematic, footnote 2 
Original text
2. Follow-up visit only for subjects who have discontinued study treatment (see Section 
5.5) or subjects who have completed the 26 week treatment period, but do not 
consent and/or are not eligible to participate in the 26 week extension study (Study 
204682).
Amended text:
2. Follow-up visit only for those subjects who discontinued investigational product (see 
Section 5.5), were withdrawn from the study, or who have completed the 26 week 
treatment period, but do not consent and/or are not eligible to participate in the 26 
week extension study (Study 204682).


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Section 4.1, Overall Design, fourth bullet point 
Original text

During the screening period, subjects will provide written informed consent and 
undergo procedures to determine eligibility for study participation. (Time and Events 
Table Section 4).
Amended text:

During the screening period, subjects will provide written informed consent and 
undergo procedures to determine eligibility for study participation. Screening will 
occur within 2 weeks of randomization. (Time and Events Table Section 7.1).
Section 4.1, Overall Design, last bullet point 
Original text

Subjects who complete the 26 week treatment period and meet all eligibility criteria 
may consent to participate in Study 204682, a 26 week extension study. 
Amended text:

Subjects, who completed the 26 week treatment period, did not discontinue 
investigational product, and meet all eligibility criteria may consent to participate in 
Study 204682, a 26 week extension study.
Section 4.2, Treatment Arms and Duration, penultimate point 
Original text

Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT 
permitted (see Section 4.4).  If a subject experiences tolerability issues with the 
higher 50mg dose then the subject may be withdrawn from the study at the 
discretion of the investigator. 
Amended text:

Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT 
permitted (see Section 4.4).  If a subject experiences tolerability issues with the 
higher 50mg dose then the subject may discontinue investigational product (at the 
discretion of the investigator) and will be followed for safety and efficacy.


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Section 4.6.1, Table 2, Risk Assessment for Albiglutide
Original text:
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) (albiglutide [GSK716155])
Identified Risks
Pancreatitis
Acute pancreatitis has been reported in association with 
albiglutide and other GLP-1 receptor agonists in clinical 
trials and during postmarketing experience.
Albiglutide has not been studied in subjects with a history 
of pancreatitis to determine whether they are at increased 
risk for pancreatitis. 
Subjects with a history of acute or chronic pancreatitis are 
excluded from entering the study (See Section 5.2).
Subjects will be informed of the characteristic symptom of 
pancreatitis: persistent severe abdominal pain. If 
pancreatitis is suspected, albiglutide should be promptly 
discontinued and if pancreatitis is confirmed, study 
treatment will not be restarted (see Section 5.5).
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Gastrointestinal (GI) events.
Albiglutide has not been studied in subjects with severe GI 
disease, including severe gastroparesis. 
Use of albiglutide can be associated with GI side effects 
such as diarrhea, nausea, and vomiting.
Subjects with severe gastroparesis are excluded from 
entering the study (See Section 5.2).
Subjects with a history of significant GI surgery that in the 
opinion of the investigator is likely to significantly affect 
upper GI or pancreatic function  are excluded from 
entering the study (See Section 5.2).
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.


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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Hypoglycemia.
Albiglutide’s mechanism of action is associated with a low 
intrinsic risk of significant hypoglycemia when used as 
monotherapy or in combination with agents such as 
metformin which also have low intrinsic risk for significant 
hypoglycemia. 
To reduce the risk of hypoglycemia when starting 
albiglutide all subjects are required to have HbA1c ≥7.0 at 
screening (see Section 5.1). 
Subjects are neither allowed to use insulin nor insulin 
secretagogues during the study. Except as part of 
hyperglycemia rescue (see Section 5.4)
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Immunogenicity 
(e.g., including anti-drug antibodies, clinical sequelae of 
antidrug antibodies, severe hypersensitivity reactions, and 
other potential immune-related AEs).
Risk assessment of the albiglutide molecule predicted low 
immunogenic potential, which was substantiated for the 
commercial lyophilized DCC pen injector product in the 
registration program. Treatment-emergent anti-drug 
antibodies were detected in ~5% subjects over studies of 
up to 3 years duration and were generally transient, of low 
titer, and not neutralizing.
Subjects who tested positive for anti-albiglutide antibodies 
experienced a similar glycemic response (HbA1c and
fasting plasma glucose) to those who did not test positive 
for antibodies. Other than injection site reactions (see 
below), the overall safety profile appeared similar among 
the subset of subjects who did and those who did not test 
positive for anti-albiglutide antibodies. 
Changes in the propensity of the liquid product to form 
aggregates could have an impact on anti-drug antibody 
characteristics or immune related AEs.  However, the 
likelihood of clinically important changes in anti-drug 
antibody characteristics or immune related AEs with the 
liquid albiglutide drug product compared to the lyophilized 
drug product is considered low based on the absence of 
substantive qualitative differences between formulations.
A pre-exposure baseline serum sample will be taken and 
tested for pre-existing ADAs.
The development of anti-albiglutide antibodies will be 
assessed as part of this study.
Hypersensitivity Reactions
Systemic allergic/hypersensitivity reactions are of potential 
concern with any injected protein and were reported rarely 
Subjects with a known allergy to albiglutide or any product 
components (including yeast and human albumin) are 


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in the Phase III program with lyophilized albiglutide. Data 
have not demonstrated an association of albiglutide with 
an increased incidence of anaphylaxis, angioedema, or 
urticaria. However, there was one non-serious 
hypersensitivity event (rash and itching associated with 
dyspnea upon rechallenge) that was consistent with a 
possible albiglutide-related systemic hypersensitivity 
reaction in a female subject who was anti-albiglutide 
antibody negative. See Section 5.4 of the IB.
excluded from the study (See Section 5.2).  
Subjects will be informed of the symptoms of severe 
hypersensitivity or allergy and be advised to seek medical 
assistance immediately. 
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
Injection site reactions (ISRs)
Albiglutide injections may cause rash, erythema or itching 
and/or other reactions at the site of injection. 
In the Phase III program with the lyophilized drug product, 
most subjects with ISRs did not test positive for anti-
albiglutide antibodies. However, injection site reactions 
were reported more frequently among those who did test
positive for anti-albiglutide antibodies (41% of the ADA 
positive subjects reported one or more injection site 
reactions) than among those who were consistently 
antibody negative (14% of the antidrug antibody negative 
subjects reported one or more injection site reactions).  
Overall, for albiglutide, injection site reactions have not 
been associated with clinically significant sequelae; 
although they can be a tolerability issue and were the most 
common reason for withdrawal of study medication for 
subjects (approximately 2.0%) in the albiglutide group.
Differences between formulation characteristics (e.g. lower 
pH and larger volume for the 50 mg dose of the liquid 
formulation) may impact the injection site reaction profile.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
The development of injection site reactions will be 
assessed as part of this study.
Other adverse reactions
(e.g., pneumonia, atrial fibrillation/atrial flutter, and 
appendicitis) 
In the Phase III program in T2DM, other possible 
albiglutide related adverse reactions were identified. These 
events occurred at a cumulative incidence <3% in studies 
up to 3 years in duration. These events were reported 
more frequently with albiglutide than comparators. See
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.


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Summary of Data/Rationale for Risk
Mitigation Strategy
Section 5.4 of the IB.
Investigational Product (IP) (albiglutide [GSK716155])
Potential Risks
Thyroid C-cell tumors
GLP-1 receptor agonists, including albiglutide increase 
serum calcitonin in rodents and other GLP-1 receptor 
agonists are associated with thyroid C-cell focal 
hyperplasia and C-cell tumors in rodents  It is unknown 
whether GLP-1 receptor agonists are associated with 
thyroid C-cell tumors in humans, including medullary 
thyroid cancer (MTC). 
Subjects with a personal or family history of MTC or 
subjects with Multiple Endocrine Neoplasia syndrome type 
2 (MEN-2) are excluded from the study (See Section 5.2).
Subjects with treatment emergent thyroid nodules should 
be referred to a specialist for evaluation in accordance with 
local treatment guidelines.  Routine monitoring of serum 
calcitonin is not recommended.  However, if serum 
calcitonin is found to be elevated the subject should be 
referred to a specialist for further evaluation. If MTC or 
other thyroid C-cell neoplasia is diagnosed, study 
treatment will be discontinued (see Section 5.5).
Other malignant neoplasms
Theoretical concerns have been raised regarding use of 
incretin based therapies and other malignancies such as 
pancreatic cancer [Egan, 2014] and malignancy when 
used in combination with insulin based on hypotheses of 
biological plausibility [European Public Assessment 
Report, 2014], and hematological malignancies [FDA
Summary Basis of Approval, 2014].
Relevant data on pancreatic cancer are summarized in IB 
Section 5.4.
Subjects with a history of cancer that has not been in full 
remission for at least 3 years before screening are 
excluded from the study (See Section 5.2).
Cardiovascular (CV) safety of antidiabetic therapy
T2DM is associated with an elevated risk of CV disease. 
Global regulatory agencies require new antidiabetic 
therapies to demonstrate that the new therapy is not 
associated with an unacceptable increase in CV risk. 
In the Phase III registration program, an independent 
Clinical Endpoint Committee prospectively adjudicated 
blinded CV events. The final CV meta-analysis showed no 
increased CV risk (MACE [major adverse cardiovascular 
event] + composed of CV death, myocardial infarction [MI], 
stroke, and hospitalization for unstable angina) with 
albiglutide versus all comparators (MACE+ hazard ratio = 
Relevant data on cardiovascular events are summarized in 
IB Section 5.4.
Subjects with clinically significant CV and/or 
cerebrovascular disease within 3 months before screening 
will be excluded from the study. Further details are 
provided in Section 5.2.
Risk communication via guidance for investigators (IB 
Section 6) and informed consent form for subjects


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1.00; 95% CI: 0.68, 1.49). See Section 5.4 of the IB.
Hepatotoxicity
Hepatotoxicity is an area of interest in drug development.  
Patients with T2DM are at increased risk for liver enzyme 
abnormalities and disease related liver conditions.  One 
subject treated with albiglutide in the Phase III clinical 
program developed probable drug induced liver injury with 
an asymptomatic elevation in alanine amino transferase 
(ALT) and total bilirubin although the cases had some 
atypical features and complicating factors . 
Routine liver safety laboratory evaluations will be 
conducted and specific withdrawal criteria for elevated liver 
function tests have been defined (See Section 5.5.4).


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Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) (albiglutide [GSK716155])
Additional Considerations
Subject population with severe renal impairment 
(estimated glomerular filtration rate (eGFR) 
<30 mL/min/1.73m2)
Experience in T2DM subjects with severe renal impairment 
is limited (in the Phase III programme a total of 19 subjects 
with eGFR <30 mL/min/1.73m2 received albiglutide). 
In a Phase III study of patients with varying degrees of 
renal impairment, in the albiglutide group, on-therapy GI 
AEs occurred with a higher incidence and higher event rate 
in subjects with moderate and severe renal impairment 
compared to those with mild renal impairment. GI events 
may lead to dehydration and worsen renal function. 
Subjects with an eGFR ≤30 mL/min/1.73 m2 (calculated 
using the Modification of Diet in Renal Disease (MDRD) 
formula) are excluded from the study (see Section 5.2).
Risk communication via guidance for investigators (see 
Section 5.4and Section 6 of the IB) and informed consent 
form for subjects.  
Drug interactions
Albiglutide causes a delay in gastric emptying, and thereby 
has the potential to impact the absorption of concomitantly 
administered oral medications.
During the development program, drug interactions 
studies were conducted with digoxin, warfarin, oral 
contraceptives, and simvastatin which demonstrated no 
clinically relevant PK or PD effects. 
Investigators will be advised to take the effect of albiglutide 
on gastric emptying into account when prescribing 
concomitant medication.
Fetal & neonatal developmental toxicity
Studies in animals have shown reproductive toxicity. The 
potential risk for humans is unknown.  Albiglutide 
administration during the major period of organogenesis in 
female mice resulted in embryofetal lethality, and 
bent/wavy ribs in the fetus at 50 mg/kg/day.  Offspring of 
mice dosed with 50 mg/kg/day during organogenesis had 
reduced pre-weaning body weight (which recovered after 
weaning), dehydration and coldness, and a delay in 
balanopreputial separation.
Given that albiglutide is an albumin-based protein 
therapeutic, it is likely to be transferred to breast milk. 
Decreased body weight in offspring was observed in mice 
treated with albiglutide during gestation and lactation.
Subjects who are breastfeeding, pregnant or planning a 
pregnancy during the course of the study are excluded. 
Additionally, all females of child-bearing potential must be 
taking adequate contraception during the study and have a 
negative pregnancy test prior to entry.  See Section 5.1 for 
further details.


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Accelerated sexual maturation in juveniles
Long-acting GLP-1R agonists have the potential to 
accelerate sexual maturation in monkeys based on 
absolute testes weight and similar trends in prostate, 
seminal vesicle, epididymides weights and histological 
assessment of maturity.
Subjects under 18 years of age are excluded (see Section 
5.1).
Study Procedures
Albiglutide matching placebo injections
Albiglutide placebo injections using the lyophilized DCC 
pen injector were associated with a clinically relevant rate 
of injection site reactions in the Phase III studies.
There is no experience with placebo injections using the 
liquid auto-injector, including volume and pH differences 
from the lyophilized product placebo.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via informed consent form for 
subjects.


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Amended text
Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
Investigational Product (IP) (albiglutide [GSK716155])
Identified Risks
Pancreatitis
Acute pancreatitis has been reported in association with 
albiglutide and other GLP-1 receptor agonists in clinical 
trials and during postmarketing experience.
Albiglutide has not been studied in subjects with a history 
of pancreatitis to determine whether they are at increased 
risk for pancreatitis. 
Subjects with a history of acute or chronic pancreatitis are 
excluded from entering the study (See Section 5.2).
Subjects will be informed of the characteristic symptom of 
pancreatitis: persistent severe abdominal pain. If 
pancreatitis is suspected, albiglutide should be promptly 
discontinued and if pancreatitis is confirmed, study 
treatment will not be restarted (see Section 5.5).
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.
Gastrointestinal (GI) events.
Albiglutide has not been studied in subjects with severe GI 
disease, including severe gastroparesis. 
Use of albiglutide can be associated with GI side effects 
such as diarrhea, nausea, and vomiting.
Subjects with severe gastroparesis are excluded from 
entering the study (See Section 5.2).
Subjects with a history of significant GI surgery that in the 
opinion of the investigator is likely to significantly affect 
upper GI or pancreatic function  are excluded from 
entering the study (See Section 5.2).
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.


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Mitigation Strategy
Hypoglycemia.
Albiglutide’s mechanism of action is associated with a low 
intrinsic risk of significant hypoglycemia when used as 
monotherapy or in combination with agents such as 
metformin which also have low intrinsic risk for significant 
hypoglycemia. 
To reduce the risk of hypoglycemia when starting 
albiglutide all subjects are required to have HbA1c ≥7.0 at 
screening (see Section 5.1). 
Subjects are neither allowed to use insulin nor insulin 
secretagogues during the study except as part of 
hyperglycemia rescue (see Section 5.4)
Risk communication via guidance for investigators (see 
the albiglutide IB) and informed consent form for 
subjects.
Immunogenicity 
(e.g., including anti-drug antibodies, clinical sequelae of 
antidrug antibodies, severe hypersensitivity reactions, and 
other potential immune-related AEs).
Risk assessment of the albiglutide molecule predicted low 
immunogenic potential, which was substantiated for the 
commercial lyophilized DCC pen injector product in the 
registration program. Treatment-emergent anti-drug 
antibodies were detected in ~5% subjects over studies of 
up to 3 years duration and were generally transient, of low 
titer, and not neutralizing.
Subjects who tested positive for anti-albiglutide antibodies 
experienced a similar glycemic response (HbA1c and 
fasting plasma glucose) to those who did not test positive 
for antibodies. Other than injection site reactions (see 
below), the overall safety profile appeared similar among 
the subset of subjects who did and those who did not test
positive for anti-albiglutide antibodies. 
Changes in the propensity of the liquid product to form 
aggregates could have an impact on anti-drug antibody 
characteristics or immune related AEs.  However, the 
likelihood of clinically important changes in anti-drug 
antibody characteristics or immune related AEs with the 
liquid albiglutide drug product compared to the lyophilized 
drug product is considered low based on the absence of 
substantive qualitative differences between formulations.
A pre-exposure baseline serum sample will be taken and 
tested for pre-existing ADAs.
The development of anti-albiglutide antibodies will be 
assessed as part of this study.
Risk communication via guidance for investigators 
(see albiglutide IB) and informed consent form for the
subject.
Hypersensitivity Reactions
Systemic allergic/hypersensitivity reactions are of potential 
concern with any injected protein and were reported rarely 
Subjects with a known allergy to albiglutide or any product 
components (including yeast and human albumin) are 


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in the Phase III program with lyophilized albiglutide. Data 
have not demonstrated an association of albiglutide with 
an increased incidence of anaphylaxis, angioedema, or 
urticaria. However, there was one non-serious 
hypersensitivity event (rash and itching associated with 
dyspnea upon rechallenge) that was consistent with a 
possible albiglutide-related systemic hypersensitivity 
reaction in a female subject who was anti-albiglutide 
antibody negative. See albiglutide IB.
excluded from the study (See Section 5.2).  
Subjects will be informed of the symptoms of severe 
hypersensitivity or allergy and be advised to seek medical 
assistance immediately. 
Risk communication via guidance for investigators (see 
albiglutide IB)) and informed consent form for subjects.
Injection site reactions (ISRs)
Albiglutide injections may cause rash, erythema or itching 
and/or other reactions at the site of injection. 
In the Phase III program with the lyophilized drug product, 
most subjects with ISRs did not test positive for anti-
albiglutide antibodies. However, injection site reactions 
were reported more frequently among those who did test 
positive for anti-albiglutide antibodies (41% of the ADA 
positive subjects reported one or more injection site 
reactions) than among those who were consistently 
antibody negative (14% of the antidrug antibody negative 
subjects reported one or more injection site reactions).  
Overall, for albiglutide, injection site reactions have not 
been associated with clinically significant sequelae; 
although they can be a tolerability issue and were the most 
common reason for withdrawal of study medication for 
subjects (approximately 2.0%) in the albiglutide group.
Differences between formulation characteristics (e.g. lower 
pH and larger volume for the 50 mg dose of the liquid 
formulation) may impact the injection site reaction profile.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.
The development of injection site reactions will be 
assessed as part of this study where the investigator or 
designee will administer both the albiglutide liquid 
drug product and the albiglutide lyophilized drug 
product.
Other adverse reactions
(e.g., pneumonia, atrial fibrillation/atrial flutter, and 
appendicitis) 
In the Phase III program in T2DM, other possible 
albiglutide related adverse reactions were identified. These 
events occurred at a cumulative incidence <3% in studies 
up to 3 years in duration. These events were reported 
more frequently with albiglutide than comparators. See 
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.


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albiglutide IB.
Investigational Product (IP) (albiglutide [GSK716155])
Potential Risks
Thyroid C-cell tumors
GLP-1 receptor agonists, including albiglutide increase 
serum calcitonin in rodents and other GLP-1 receptor 
agonists are associated with thyroid C-cell focal 
hyperplasia and C-cell tumors in rodents  It is unknown 
whether GLP-1 receptor agonists are associated with 
thyroid C-cell tumors in humans, including medullary 
thyroid cancer (MTC). 
Subjects with a personal or family history of MTC or 
subjects with Multiple Endocrine Neoplasia syndrome type 
2 (MEN-2) are excluded from the study (See Section 5.2).
Subjects with treatment emergent thyroid nodules should 
be referred to a specialist for evaluation in accordance with 
local treatment guidelines.  Routine monitoring of serum 
calcitonin is not recommended.  However, if serum 
calcitonin is found to be elevated the subject should be 
referred to a specialist for further evaluation. If MTC or 
other thyroid C-cell neoplasia is diagnosed, study 
treatment will be discontinued (see Section 5.5).
Other malignant neoplasms
Theoretical concerns have been raised regarding use of 
incretin based therapies and other malignancies such as 
pancreatic cancer [Egan, 2014] and malignancy when 
used in combination with insulin based on hypotheses of 
biological plausibility [European Public Assessment 
Report, 2014], and hematological malignancies [FDA
Summary Basis of Approval, 2014].
Relevant data on pancreatic cancer are summarized in the 
albiglutide IB.
Subjects with a history of cancer that has not been in full 
remission for at least 3 years before screening are 
excluded from the study (See Section 5.2). A history of 
squamous cell or basal cell carcinoma of the skin or 
treated cervical intra-epithelial neoplasia I or II is 
allowed.
Cardiovascular (CV) safety of antidiabetic therapy
T2DM is associated with an elevated risk of CV disease. 
Global regulatory agencies require new antidiabetic 
therapies to demonstrate that the new therapy is not 
associated with an unacceptable increase in CV risk. 
In the Phase III registration program, an independent 
Clinical Endpoint Committee prospectively adjudicated 
blinded CV events. The final CV meta-analysis showed no 
increased CV risk (MACE [major adverse cardiovascular 
event] + composed of CV death, myocardial infarction [MI], 
stroke, and hospitalization for unstable angina) with 
Relevant data on cardiovascular events are summarized in 
IB Section 5.4.
Subjects with clinically significant CV and/or 
cerebrovascular disease within 3 months before screening 
will be excluded from the study. Further details are 
provided in Section 5.2


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albiglutide versus all comparators (MACE+ hazard ratio = 
1.00; 95% CI: 0.68, 1.49). See Section 5.4 of the IB.
Hepatotoxicity
Hepatotoxicity is an area of interest in drug development.  
Patients with T2DM are at increased risk for liver enzyme 
abnormalities and disease related liver conditions.  One 
subject treated with albiglutide in the Phase III clinical 
program developed probable drug induced liver injury with 
an asymptomatic elevation in alanine amino transferase 
(ALT) and total bilirubin although the cases had some 
atypical features and complicating factors . 
Routine liver safety laboratory evaluations will be 
conducted and specific withdrawal criteria for elevated liver 
function tests have been defined (See Section 5.5.4).


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Investigational Product (IP) (albiglutide [GSK716155])
Additional Considerations
Subject population with severe renal impairment 
(estimated glomerular filtration rate (eGFR) 
<30 mL/min/1.73m2)
Experience in T2DM subjects with severe renal impairment 
is limited (in the Phase III programme a total of 19 subjects 
with eGFR <30 mL/min/1.73m2 received albiglutide). 
In a Phase III study of patients with varying degrees of 
renal impairment, in the albiglutide group, on-therapy GI 
AEs occurred with a higher incidence and higher event rate 
in subjects with moderate and severe renal impairment 
compared to those with mild renal impairment. GI events 
may lead to dehydration and worsen renal function. 
Subjects with an eGFR ≤30 mL/min/1.73 m2 (calculated 
using the Modification of Diet in Renal Disease (MDRD) 
formula) are excluded from the study (see Section 5.2).
Risk communication via guidance for investigators (see 
albiglutide IB) and informed consent form for subjects.  
Drug interactions
Albiglutide causes a delay in gastric emptying, and thereby 
has the potential to impact the absorption of concomitantly 
administered oral medications.
During the development program, drug interactions 
studies were conducted with digoxin, warfarin, oral 
contraceptives, and simvastatin which demonstrated no 
clinically relevant PK or PD effects. 
Investigators will be advised to take the effect of albiglutide 
on gastric emptying into account when prescribing 
concomitant medication.
Fetal & neonatal developmental toxicity
Studies in animals have shown reproductive toxicity. The 
potential risk for humans is unknown.  Albiglutide 
administration during the major period of organogenesis in 
female mice resulted in embryofetal lethality, and 
bent/wavy ribs in the fetus at 50 mg/kg/day.  Offspring of 
mice dosed with 50 mg/kg/day during organogenesis had 
reduced pre-weaning body weight (which recovered after 
weaning), dehydration and coldness, and a delay in 
balanopreputial separation.
Given that albiglutide is an albumin-based protein 
therapeutic, it is likely to be transferred to breast milk. 
Decreased body weight in offspring was observed in mice 
treated with albiglutide during gestation and lactation.
Subjects who are breastfeeding, pregnant or planning a 
pregnancy during the course of the study are excluded. 
Additionally, all females of child-bearing potential must be 
taking adequate contraception during the study and have a 
negative pregnancy test prior to entry.  See Section 5.1 for 
further details.
Risk communication via guidance for investigators 
(see albiglutide IB) and informed consent form for 
subjects.


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Accelerated sexual maturation in juveniles
Long-acting GLP-1R agonists have the potential to 
accelerate sexual maturation in monkeys based on 
absolute testes weight and similar trends in prostate, 
seminal vesicle, epididymides weights and histological 
assessment of maturity.
Subjects under 18 years of age are excluded (see Section 
5.1).
Study Procedures
Albiglutide matching placebo injections
Albiglutide placebo injections using the lyophilized DCC 
pen injector were associated with a clinically relevant rate 
of injection site reactions in the Phase III studies.
There is no experience with placebo injections using the 
liquid auto-injector, including volume and pH differences 
from the lyophilized product placebo.
Subjects will be advised that when injecting in the same 
region, to use a different injection site each week.
Risk communication via informed consent form for 
subjects.


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Section 5.1 Inclusion Criteria 2
Original text
2.
Historical diagnosis of T2DM (at least 3 months), experiencing inadequate glycemic 
control on current regimen of diet and exercise or on a stable maximal tolerated dose 
of metformin, maintained for approximately 8 weeks prior to screening.
Amended text:
2.
Historical diagnosis of T2DM (at least 3 months), experiencing inadequate glycemic 
control on current regimen of diet and exercise or on a stable dose of metformin of 
at least 1500 mg or the documented maximal tolerated dose if less than 1500 mg 
metformin (monotherapy), maintained for approximately 8 weeks prior to screening
Section 5.2 Exclusion Criteria 14
Original text
14. eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula) at screening.
Note: As the use of metformin in subjects with varying degrees of renal function 
may differ from country to country, use of metformin should be in accordance 
with the metformin product label within the participating country.
Amended text:
25. eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula) at screening.
Note: The use of metformin in subjects with varying degrees of renal function   
should be in accordance with the metformin product label.
Section 5.2 Exclusion Criteria 18
Original text
18. Use of dipeptidyl peptidase-IV inhibitors within the 3 months before randomization.
Amended text:
18. Use of GLP 1 receptor agonists at any time. Use of dipeptidyl peptidase-IV 
inhibitors within the 3 months before randomization. Use of any other antidiabetic 
medications with the exception of metformin within 3 weeks before randomization.
Section 5.5 Withdrawal/Stopping Criteria
Original text
5.5  Withdrawal/Stopping Criteria
Every effort should be made to keep subjects in the study. The reason for a subject not 
completing the study will be recorded in the subject’s electronic case report form 
(eCRF).


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Any subject experiencing the following will be required to discontinue investigational 
product and will be withdrawn from the study:

Any AE, which, in the opinion of the investigator precludes effective participation of 
the subject or poses a safety concern

The following AEs will require withdrawal:

Confirmed pancreatitis, acute or chronic. 

Pancreatic cancer.

Confirmed MTC or other thyroid C-cell neoplasia.  

Liver chemistry abnormalities exceeding the threshold criteria outlined in 
Section 5.5.4

QTc abnormalities exceeding the threshold criteria outlined in Section 5.5.5.

Severe allergic/hypersensitivity reactions that are considered by the 
investigator to be attributable to investigational product or without a likely 
alternative aetiology.

eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula).

Subject becomes pregnant or intends to become pregnant during the study.

Need for chronic use of a prohibited concomitant medication (Section 6.10.2)

Major protocol deviation (the investigator should discuss the protocol deviation with 
the medical monitor before withdrawing study medication)

Subject decision (reason to be documented in the eCRF, if specified by the subject)

Investigator discretion 

Study closed/terminated or investigator site closed (where subject transfer to another 
site is not possible)
The following actions must be taken in relation to a subject who fails to attend the clinic 
for a required study visit:

The site must attempt to contact the subject and re-schedule the missed visit as soon 
as possible. 

The site must counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 

In cases where the subject is deemed ‘lost to follow up’, the investigator or designee 
must make every effort to regain contact with the subject (where possible, 3 telephone 
calls and if necessary a certified letter to the subject’s last known mailing address or 
local equivalent methods). These contact attempts should be documented in the 
subject’s medical record. 


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
Should the subject continue to be unreachable, only then will he/she be considered to 
have withdrawn from the study with a primary reason of “Lost to Follow-up”. 
Subjects who are withdrawn or discontinue active participation in the study will no 
longer receive the randomized study treatment. Immediately upon discontinuation from 
active participation in this study, these subjects should complete the assessments as per 
the end of treatment clinic visit and return for the post-treatment follow-up clinic visit 8 
weeks later (Section 7.1). If a subject is unable or unwilling to return for the follow-up 
assessments, every effort will be made to follow-up with the subject.
Withdrawn subjects will not be replaced. 
A subject may withdraw from study treatment at any time at his/her own request, or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioral 
or administrative reasons. If a subject withdraws from the study, he/she may request 
destruction of any samples taken, and the investigator must document this in the site 
study records. 
Amended text:
5.5  Withdrawal/Stopping Criteria
Every effort should be made to keep subjects in the study. The reason for a subject 
discontinuing investigational product or withdrawing from the study will be recorded 
in the subject’s electronic case report form (eCRF). 
5.5.1  Permanent Discontinuation of Investigational Product
A subject may permanently discontinue investigational product at any time at his/her 
own request, or at the discretion of the investigator for safety or compliance reasons.  A 
subject must permanently discontinue investigational product for the pre-specified 
reasons below. 

Any AE, which, in the opinion of the investigator precludes effective participation of 
the subject or poses a safety concern

The following AEs will require discontinuation from investigational product:

Confirmed pancreatitis, acute or chronic. 

Pancreatic cancer.

Confirmed MTC or other thyroid C-cell neoplasia.  

Liver chemistry abnormalities exceeding the threshold criteria outlined in 
Section 5.5.4

QTc abnormalities exceeding the threshold criteria outlined in Section 5.5.5.

Severe allergic/hypersensitivity reactions that are considered by the 
investigator to be attributable to investigational product or without a likely 
alternative aetiology.


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
eGFR ≤30 mL/min/1.73 m2 (calculated using the MDRD formula).

Subject becomes pregnant or intends to become pregnant during the study.

Need for chronic use of a prohibited concomitant medication (Section 6.10.2)

Major protocol deviation (the investigator should discuss the protocol deviation with 
the medical monitor before withdrawing study medication)

Subject decision (reason to be documented in the eCRF, if specified by the subject)

Investigator discretion 

Study closed/terminated or investigator site closed (where subject transfer to another 
site is not possible)
In all cases, the reasons for investigational product discontinuation and the date of the 
last dose will be recorded in the subject’s electronic case report form (eCRF) and the 
subject will continue in the study as described in 5.5.1.1.
5.5.1.1  Procedures for Subject Follow-up Following Discontinuation of 
Investigational Product
Subjects will be educated on the importance of remaining in the study and attending all 
scheduled study visits. 
Subjects who permanently discontinue investigational product will be expected to 
attend clinic visits every 4 weeks through the End of Treatment visit, according to the 
study visit schedule, unless consent is actively withdrawn. Complete details are 
provided in the Time and Events Table (Section 7.1).
If a subject is unable or unwilling to continue attending clinic visits in person, other 
subject follow-up options to collect subject information as detailed in the informed 
consent (e.g., telephone calls, letters, review of subjects medical records) should be 
pursued.
5.5.2  Subjects Who Fail to Attend Clinic Visits
The following actions must be taken in relation to a subject who fails to attend the clinic 
for a required study visit:

The site must attempt to contact the subject and re-schedule the missed visit as soon 
as possible. 

The site must counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 

In cases where the subject is deemed ‘lost to follow up’, the investigator or designee 
must make every effort to regain contact with the subject (where possible, 3 telephone 
calls and if necessary a certified letter to the subject’s last known mailing address or 
local equivalent methods). These contact attempts should be documented in the 
subject’s medical record. 


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
Should the subject continue to be unreachable, only then will he/she be considered to 
have withdrawn from the study with a primary reason of “Lost to Follow-up”. 
5.5.3  Withdrawal from Study
Every effort should be made to keep subjects in the study. For subjects that choose to 
withdraw consent or are lost to follow up, the reason for not completing the study will 
be recorded in the subject’s eCRF. If a subject withdraws from the study, he/she may 
request destruction of any samples taken, and the investigator must document this in the 
site study records. 
Subjects who are withdrawn or discontinue active participation in the study will no 
longer receive the randomized study treatment. Immediately upon discontinuation from 
active participation in this study, these subjects should complete the assessments as per 
the end of treatment clinic visit and return for the post-treatment follow-up clinic visit 8 
weeks later (Section 7.1). If a subject is unable or unwilling to return for the follow-up 
assessments, every effort will be made to follow-up with the subject.
Withdrawn subjects will not be replaced. 
Section 5.5.5  QTC Stopping Criteria, 3rd bullet.
Original text

A subject who meets the following criteria will be withdrawn from the study:
Amended text:

A subject who meets the following criteria will discontinue investigational product:
Section 6.3  Planned Dose Adjustments, 2nd paragraph.
Original text

Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT 
permitted (see Section 4.4).  If a subject experiences tolerability issues with the 
higher 50mg dose then the subject may be withdrawn from the study at the 
discretion of the investigator. 
Amended text:

Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT 
permitted.  If a subject experiences tolerability issues with the higher 50mg dose then 
the subject may discontinue investigational product (at the discretion of the 
investigator) and be followed for safety and efficacy.


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Section 6.3  Planned Dose Adjustments, 3rd  paragraph.
Original text
Subjects on a stable dose of metformin at the start of the study may have their 
metformin dose adjusted at the discretion of the investigator based on clinical need.
Amended text:
The use of metformin in subjects with varying degrees of renal function should be in 
accordance with the metformin product label. It is encouraged that a stable metformin 
dose is maintained during the study. However the metformin dose may be downtitrated 
based on clinical need at the discretion of the investigator. Up-titration of metformin is 
permitted for subjects who require hyperglycemic rescue and metformin is selected as 
the rescue medication.
Section 6.4  Blinding, penultimate bullet.
Original text

A subject will be withdrawn if the subject’s treatment code is unblinded by the 
investigator or treating physician. The primary reason for discontinuation (the 
event or condition which led to the unblinding) will be recorded in the eCRF.
Amended text:

If the subject’s treatment code is unblinded by the investigator or treating 
physician the subject will continue to receive treatment unless they meet one of the 
investigational product discontinuation or study withdrawal criteria outlined in 
Section 5.5
Section 7 Study Assessments and Procedures, last sentence.
Original text
The medical monitor shall make a decision (on a case by case basis) on whether the 
subject should be withdrawn from the study.
Amended text:
The medical monitor shall make a decision (on a case by case basis) on whether the 
subject should continue to receive investigation product.
Table 4 Study Assessments, footnote 15
Original text
15. Follow-up visit for subjects who have discontinued study treatment (see Section 5.5)
or subjects who have completed the 26 week treatment period, but do not consent 
and/or are not eligible to participate in the 26 week extension study (Study 204682).
Amended text:


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15. Follow-up visit for those subjects who have stopped investigational product (see 
Section 5.5), withdrawn from the study or  who have completed the 26 week 
treatment period, but do not consent and/or are not eligible to participate in the 26 
week extension study (Study 204682).
Table 4 Schedule of Assessments, footnote 5
Footnote removed
Urine samples should be collected in the early morning.
Table 4 Schedule of Assessments, footnote 16
Footnote added
All visits will have a treatment window as in the table> Subjects will not be considered 
out of compliance if visit windows extend because of extraordinary events that make it 
impossible for  subjects to complete a visit within the above window (e.g., holidays, 
vacations, personal emergencies). Determination of the maximum visit window deviation 
is at the discretion of the medical monitor


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Table 4 Schedule of Assessments
Original text
Procedure
Treatment
End of 
Treatment
13,14
Follow-
up15
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
Procedure
Treatment
End of 
Treatment
13,14
Follow-
up15
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
Amended text
Procedure
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Week
-2
0
1
2
3
4
5
6
7
8
9
10
11
12
Visit Window
-14d
0d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
Procedure
Treatment
End of 
Treatment1
3,14
Follow-
up15
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
Visit Window
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±7d


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Table 5 Study Assessments for Subjects Who Permanently Discontinue Investigational Product
New text
Table 5 Schedule of Assessments for Subjects Who Permanently Discontinue Investigational Product 
Procedure
Continue Scheduled Clinic Visit 
(Weeks 4, 8, 12, 16, 20) 4,5
Week 26 
(Equivalent to End of Treatment 
Visit)
Follow-up 
Week 34
Full (F) or brief (B) physical exam
B
F
F
Weight
X
X
X
12-lead ECG 1
X
X
Vital Signs
X
X
X
Clinical chemistry/hematology samples2
X
X
X
HbA1c and FPG 3
X
X
X
Review AE/SAE, concomitant medication and hypoglycemia 
events
X
X
X
1.
12-lead ECGs will be obtained before measurement of vital signs and collection of blood samples for laboratory testing. Vital signs measurement will be taken before collection of 
blood samples. See Section 7.4.5.
2.
Clinical chemistry and hematology assessments are described in Section 7.4.6.
3.
Subjects will have their FPG and HbA1c levels evaluated to monitor for potential hyperglycemia.
4.
Week will be dependent on when the subject discontinues investigational product. Subjects will start this schedule as soon as possible following investigational product 
discontinuation and timings of visits will be the same as for if the subject was continuing on investigational product. The timing of the clinic visits can be modified at the discretion 
of the investigator. All subjects must attend the Week 26 visit.
5.
Additional unscheduled visits will occur as medically necessary


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Section 7.4.1.5 AEs of Special Interest, last paragraph
Original text
Subjects with drug hypersensitivity reactions that are not reasonably attributable to 
another cause or pancreatitis should be withdrawn from the study and should not be 
rechallenged with albiglutide (see Section 5.5 for complete list of AEs of special interest 
requiring withdrawal).
Amended text:
Subjects with drug hypersensitivity reactions that are not reasonably attributable to 
another cause or pancreatitis should discontinue investigational product and should not 
be rechallenged with albiglutide (see Section 5.5 for complete list of AEs of special 
interest requiring withdrawal).
Section 7.4.3. Physical Exams, penultimate sentence
Original text
Weight will be measured at each clinic visit.
Amended text:
Weight will be measured at the time points specified in the Time and Events Table 
Section 7.1
Section 7.4.6. Clinical Safety Laboratory Assessments, penultimate paragraph, last 
scentence
Original text
The results of the test must be entered into the eCRF.
Amended text:
HbA1c results from a local laboratory must be entered into the eCRF.
Section 9.4 Key Elements of Analysis Plan
Original text
9.4  Key Elements of Analysis Plan
9.4.1  Primary Analyses
The primary endpoint is the change from baseline in HbA1c at Week 26. The primary 
analysis of the primary endpoint will be conducted using a mixed-effect model with 
repeated measures (MMRM) in the ITT Population. MMRM will use all available data 
(including post-hyperglycemia rescue data). Analysis excluding post-rescue HbA1c 
data will also be performed as supportive and is described in Section 9.4.5.


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The model will include HbA1c change from baseline at all post-baseline visits as 
dependent variables; treatment, region, age category, weight, background antidiabetic 
therapy, visit week, and treatment-by-week interaction as fixed effects; baseline HbA1c 
as a continuous covariate; and subject as a random effect. Treatment effects estimates 
(and associated CI) of albiglutide liquid drug product will be evaluated within this 
MMRM model as least squares means contrasts relative to the lyophilized drug product. 
An unstructured covariance matrix will be used for the MMRM analysis, unless the 
model does not converge, in which case the covariance matrix will be decided upon 
model convergence status and the Akaike information criterion. 
The primary analysis will include all HbA1c values collected at scheduled visits up to 
Week 26. This will include values after hyperglycemia rescue. Missing data, in the 
context of the primary analysis at Week 26, refer to those cases where the Week 26 
HbA1c value is not available or was not collected.
The primary endpoint HbA1c change from baseline at Week 26 may also be analyzed 
using the same MMRM model in the PP Population if needed as a supportive analysis.
Special attention will be paid to the handling of missing data in statistical analysis. 
Although, it is expected that the pattern of missing data will be similar in both 
treatment arms given that the treatment arms are the same drug but different 
formulations. The method for the primary analysis, MMRM, assumes missing at 
random. The sensitivity of the results of analysis to the method of handling missing 
values will be investigated, especially if the number of missing values is substantial or 
if the characteristics of missing values differ between treatment groups. Further details 
of the sensitivity analysis, including imputation methods and assumptions about the 
missing data are described in Section 9.4.5.4.
9.4.2  Secondary Analyses
The evaluation of the safety and tolerability as assessed by immunogenicity and ISRs of 
albiglutide liquid drug product and the lyophilized drug product will be provided by 
reporting the event rates, and the associated 95% CI.
The overall general safety and tolerability of albiglutide liquid drug product versus 
lyophilized drug product will be evaluated in tabular and/or graphical format and 
summarized descriptively. 
AEs and SAEs, physical examinations, clinical laboratory evaluations, vital sign 
measurements, and 12-lead electrocardiogram will be summarized by treatment group. 
For continuous variables, these summaries will include sample size, mean, median, 
standard deviation (and/or standard error), minimum, and maximum. For categorical 
variables, the summaries will include frequencies and corresponding percentages. The 
exposure-adjusted incidence rate will also be calculated as the number of events in a 
given period divided by the total person time on treatment of subjects at risk within the 
same period. The exposure-adjusted incidence rate will be expressed as an annualized 
rate expected.  No inferential testing will be performed on the safety variables. 


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Hypoglycemic events will be analyzed separately from other AEs. All hypoglycemic 
events will be classified as severe, documented symptomatic, asymptomatic, probable 
symptomatic, and pseudohypoglycemia, as defined in Section 7.4.9.
AEs will be coded using MedDRA. AEs will be summarized in various subsets, including 
on therapy AEs, related AEs, AEs leading to treatment discontinuation or withdrawal 
from study, SAEs, fatal AEs, etc. AEs will also be summarized by maximum intensity 
(mild, moderate, and severe).
Anti-albiglutide antibody results will be summarized by treatment group. In addition, the 
number and percentage of subjects with positive results along with the antibody titer 
values will be provided by visit. 
The secondary endpoint FPG change from baseline at Week 26 will be analyzed 
analogous to the primary endpoint HbA1c using MMRM.
To assess the PD effect of albiglutide over time for the secondary endpoints change from 
baseline in HbA1c over time and change from baseline in FPG over time MMRM models 
will be used. The model will include HbA1c or FPG change from baseline at all post-
baseline visits as dependent variables; treatment, visit week, and treatment-by-week 
interaction as fixed effects; baseline HbA1c or FPG as a continuous covariate; and 
subject as a random effect. Treatment effects estimates (and associated CI) of albiglutide 
liquid drug product will be evaluated within this MMRM model as least squares means 
contrasts relative to the lyophilized drug product. An unstructured covariance matrix will 
be used for the MMRM analysis, unless the model does not converge, in which case the 
covariance matrix will be decided upon model convergence status and the Akaike 
information criterion. In addition, PD effect of albiglutide over time for both HbA1c and 
FPG change from baseline over time will be evaluated in tabular and/or graphical format 
and summarized descriptively.
PK trough plasma concentration data will be summarized by treatment. No formal 
statistical analyses will be conducted.
9.4.3  Other Analyses
The analyses of the primary and secondary efficacy endpoints are described in Section 
9.4.1 and Section 9.4.2. The details of any further planned analyses, including subgroup 
analysis and exploratory endpoints, will be provided in the RAP.
9.4.4  Supportive Analysis for Primary Endpoint: Exclusion of Data after 
Rescue
It is not expected to have a substantial number of subjects who will require rescue and 
that number of subjects would be similar for both treatment arms.  However, to assess 
the impact of rescue, analysis of pre-rescue data will be performed. The model will be 
similar to the one used for the primary analysis. Results of this analysis will 
supplement the primary analysis. In addition, exclusion of data after treatment 


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discontinuation may also be performed if a significant number of subjects discontinue 
study medication prior to Week 26.
9.4.5  Missing Data
9.4.5.1  Impact of Missing Data on Primary Endpoint
Missing data, in the context of the primary analysis at Week 26, refer to those cases 
where the Week 26 HbA1c value is not available or was not collected. Missing data are 
not explicitly imputed in the primary MMRM analysis; although, there is an 
underlying assumption that data are missing at random. It is expected that the pattern 
of missing data will be similar in both treatment arms given that the treatment arms are 
the same drug but different formulas. All available scheduled post-baseline 
assessments up to endpoint are utilized and, via modeling of the within subject 
correlation structure, the derived treatment difference at Week 26 is adjusted to take 
into account missing data. The MMRM analysis (using saturated fixed effects and an 
unstructured variance-covariance matrix) is considered appropriate as the primary 
method of analysis, as it has been shown to give sensible answers to on-treatment 
questions in a range of practical situations [Siddiqui, 2009].
9.4.5.2  Extent of Missing Primary Analysis Data
Missing data is expected to arise mainly from subjects missing complete visits. The 
amount of missing data for those baseline covariates included in the statistical analysis is 
expected to be none or at worst minimal. If it should occur, that subject will effectively 
be lost to analysis. Missing data for HbA1c between two non-missing visits will be 
considered missing at random (intermediate missing data).
In this study, subjects who withdraw from treatment will be withdrawn from the study. In 
the eCRF, the reason for treatment discontinuation and the reason for withdrawal from 
the study are collected separately. Whenever the HbA1c value at Week 26 is missing 
(end of the study), the reason can be determined based on available data in these two 
locations.
The reason for missing data can be classified as follows: safety or  procedural 
(including withdrawal of consent).
9.4.5.3  Reasons for Withdrawal
Reasons for withdrawal are assumed to fall into three broad categories:

Procedural (e.g., lost to follow-up, withdrew consent, protocol deviation, study 
closed/terminated, and investigator discretion): In this case, it is expected that 
an assumption of missing at random (MAR) is appropriate for imputation of 
HbA1c data after withdrawal.

Safety (e.g., AE, subject reached protocol-defined stopping criteria): It is 
expected that, in most cases, any change in safety related to these reasons for 
withdrawal would have been captured prior to the subject withdrawing from 


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the study. Missing HbA1c values after withdrawal due to safety concerns will 
be considered to possibly be missing not at random (MNAR).
Sensitivity analyses will be performed for data missing due to safety concerns.
9.4.5.4  Handling of Missing Data
The impact of missing data will be explored, as outlined below, for the ITT Analysis 
Population only.
Examination of Missing Data Patterns
It is expected that the pattern of missing data will be similar in both treatment arms given 
that each treatment arm is using the same drug but different formula. 
To examine the nature of missing data, cohorts of subjects will be defined based on the 
scheduled assessments (HbA1c change from baseline) that were completed at Weeks 1, 
4, 8, 12, 16, 20, and 26.

Subjects who have week 1 assessment only

Subjects who have assessments up to and including Week 4 only

Subjects who have assessments up to and including Week 8 only

Subjects who have assessments up to and including Week 12 only

Subjects who have assessments up to and including Week 16 only

Subjects who have assessments up to and including Week 20 only

Subjects who have assessments up to and including Week 26.
The number and percentage of subjects on each treatment in the 7 cohorts defined here 
will be tabulated. Graphical methods will be used to examine changes from baseline over 
time to assess the pattern of outcomes prior to withdrawal.
Sensitivity Analyses – Multiple Imputation
Sensitivity analyses using multiple imputation methods will be conducted. Firstly, 
missing data between two non-missing time points will be considered missing at 
random.
The following multiple imputation methods are proposed based on whether data are 
missing at random or not missing at random:

All missing data assumed MAR: Imputation is based on means and variances-
covariances from subjects in the same treatment group as the withdrawn subject 
and is comparable to MMRM. The main differences are that this approach uses 
separate covariance parameter estimation for each arm, and also separate 
regression parameters are estimated on baseline covariates within each arm. This 
more complex parameterization of the imputation model compared with the 
analysis model is valid. This approach will be used for all data missing post 


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withdrawal. Here the estimand is one where after withdrawal all subjects progress 
in a similar way to those who remain in the trial. We expect the MMRM and this to 
give similar inference. If so, then it indicates any difference between the primary 
MMRM analysis and multiple imputation sensitivity analysis is due to the assumed 
effect modification and the assumed rates of HbA1c increase after withdrawal, 
rather than anything to do with going from an MMRM approach to a multiple 
imputation approach. 

Missing due to the values of Week 26 HbA1c is not available or was not collected 
or due to safety concerns using last mean carried forward (LMCF) that is MNAR: 
This approach assumes that a constant rate of increase in HbA1c change from 
baseline is experienced by subjects following withdrawal from the study due to 
safety concerns. The MAR approach will be used for missing data due to 
procedural reasons. Sensitivity analyses using the LMCF approach will be 
performed using the following rates of HbA1c increase: 0%/month, 0.1%/month, 
and 0.2%/month to explore the potential impact as in a tipping-point analysis. For 
each treatment group, these 3 rates will be assumed, resulting in 9 scenarios. The 
resulting treatment differences and associated P-values for non-inferiority will be 
tabulated against the varying rates of HbA1c increase. This estimand is one where 
those who withdraw for safety concerns are assumed to revert to an unstable 
treatment regimen with an increasing rate of HbA1c. 
For each imputation data set, an analysis of variance will be carried using Week 26 
data, both actual and imputed, using the same covariates as in the primary analysis. 
Contrasts of interest will be estimated and then combined across imputations using 
standard multiple imputation rules.
Additional scenarios for sensitivity analysis may be added and described in the RAP.
Amended text:
9.4  Key Elements of Analysis Plan
9.4.1  Primary Analyses
The primary endpoint is the change from baseline in HbA1c at Week 26. The primary 
analysis will include all HbA1c values collected at scheduled visits up to Week 26. This 
will include values after hyperglycemia rescue and discontinuation from 
investigational product. The primary analysis of the primary endpoint will be 
conducted using a mixed-effect model with repeated measures (MMRM) in the ITT 
Population. MMRM will use all available data.  Imputation under the non-inferiority 
null hypothesis for missing data will be incorporated [Koch, 2008]. Multiple imputation 
will be used to replace missing data of change from baseline of HbA1c at Week 26 for
all patients in both treatment arms as a first step, and then to make all the imputed 
values for the liquid drug product arm worse by the non-inferiority margin 0.4. 
Multiple imputation approach uses separate covariance parameter estimation for each 
arm, and also separate regression parameters are estimated on baseline covariates 
within each arm. For subjects with missing data the imputation will use means and 


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variances-covariances from subjects in that treatment group where that subject with 
missing data belongs. This approach will be used for all data missing post withdrawal 
due to lost to follow-up or withdraws consent. 
Non-inferiority testing will be performed at a one-sided alpha of 0.025 and non-
inferiority margin of 0.4. 
Further details of the imputation method for the primary analysis will be provided in 
the RAP.
The primary MMRM model will include HbA1c change from baseline at all post-baseline 
visits as dependent variables; treatment, region, age category, weight, background 
antidiabetic therapy, visit week, and treatment-by-week interaction as fixed effects; 
baseline HbA1c as a continuous covariate; and subject as a random effect. Treatment 
effects estimates (and associated CI) of albiglutide liquid drug product will be evaluated 
within this MMRM model as least squares means contrasts relative to the lyophilized 
drug product. An unstructured covariance matrix will be used for the MMRM analysis, 
unless the model does not converge, in which case the covariance matrix will be decided 
upon model convergence status and the Akaike information criterion. 
9.4.2  Secondary Analyses
The evaluation of the safety and tolerability as assessed by immunogenicity and ISRs of 
albiglutide liquid drug product and the lyophilized drug product will be provided by 
reporting the event rates, and the associated 95% CI.
The overall general safety and tolerability of albiglutide liquid drug product versus 
lyophilized drug product will be evaluated in tabular and/or graphical format and 
summarized descriptively. 
AEs and SAEs, physical examinations, clinical laboratory evaluations, vital sign 
measurements, and 12-lead electrocardiogram will be summarized by treatment group. 
For continuous variables, these summaries will include sample size, mean, median, 
standard deviation (and/or standard error), minimum, and maximum. For categorical 
variables, the summaries will include frequencies and corresponding percentages. The 
exposure-adjusted incidence rate will also be calculated as the number of events in a 
given period divided by the total person time on treatment of subjects at risk within the 
same period. The exposure-adjusted incidence rate will be expressed as an annualized 
rate expected.  No inferential testing will be performed on the safety variables. 
Hypoglycemic events will be analyzed separately from other AEs. All hypoglycemic 
events will be classified as severe, documented symptomatic, asymptomatic, probable 
symptomatic, and pseudohypoglycemia, as defined in Section 7.4.9.
AEs will be coded using MedDRA. AEs will be summarized in various subsets, including 
on therapy AEs, related AEs, AEs leading to treatment discontinuation or withdrawal 
from study, SAEs, fatal AEs, etc. AEs will also be summarized by maximum intensity 
(mild, moderate, and severe).


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Anti-albiglutide antibody results will be summarized by treatment group. In addition, the 
number and percentage of subjects with positive results along with the antibody titer 
values will be provided by visit. 
The secondary endpoint FPG change from baseline at Week 26 will be analyzed using 
MMRM without imputation.
To assess the PD effect of albiglutide over time for the secondary endpoints change from 
baseline in HbA1c over time and change from baseline in FPG over time MMRM models 
will be used. The model will include HbA1c or FPG change from baseline at all post-
baseline visits as dependent variables; treatment, visit week, and treatment-by-week 
interaction as fixed effects; baseline HbA1c or FPG as a continuous covariate; and 
subject as a random effect. Treatment effects estimates (and associated CI) of albiglutide 
liquid drug product will be evaluated within this MMRM model as least squares means 
contrasts relative to the lyophilized drug product. An unstructured covariance matrix will 
be used for the MMRM analysis, unless the model does not converge, in which case the 
covariance matrix will be decided upon model convergence status and the Akaike 
information criterion. In addition, PD effect of albiglutide over time for both HbA1c and 
FPG change from baseline over time will be evaluated in tabular and/or graphical format 
and summarized descriptively.
PK trough plasma concentration data will be summarized by treatment. No formal 
statistical analyses will be conducted.
9.4.3  Other Analyses
The analyses of the primary and secondary efficacy endpoints are described in Section 
9.4.1 and Section 9.4.2. The details of any further planned analyses, including subgroup 
analysis and exploratory endpoints, will be provided in the RAP.
9.4.4  Supportive Analyses for Primary Endpoint
The primary endpoint change from baseline in HbA1c at Week 26 will be analyzed 
using the same MMRM model as described in Section 9.4.1 but missing data are not 
explicitly imputed in this supportive analysis; although, there is an underlying 
assumption that data is missing at random. All available scheduled post-baseline 
assessments up to endpoint are utilized and, via modeling of the within subject 
correlation structure, the derived treatment difference at Week 26 is adjusted to take 
into account missing data. The MMRM analysis (using saturated fixed effects and an 
unstructured variance-covariance matrix) is considered appropriate as the supportive 
analyses, as it has been shown to give sensible answers to on-treatment questions in a 
range of practical situations [Siddiqui, 2009].
Analysis excluding post-rescue and/or discontinuation from investigational product 
HbA1c data will also be performed as supportive.  It is not expected to have a 
substantial number of subjects who will require rescue and that number of subjects 
would be similar for both treatment arms.  However, to assess the impact of rescue, 
analysis of pre-rescue data will be performed. The MMRM model will be similar to the 


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one used for the primary analysis.  Results of this analysis will supplement the primary 
analysis. No imputation will be conducted for this supportive analysis.
The primary endpoint HbA1c change from baseline at Week 26 may also be analyzed 
using MMRM model in the PP Population, if sample size is sufficient, imputation will 
not be conducted for this supportive analysis. 
Further details of the supportive analyses will be provided in the RAP.
9.4.5  Missing Data
9.4.5.1  Impact of Missing Data on Primary Endpoint
Missing data, in the context of the primary analysis at Week 26, refer to those cases 
where the Week 26 HbA1c value is not available or was not collected or subject is lost 
to follow-up or withdraws consent. Missing data will be imputed in the primary 
MMRM analysis. To avoid bias in non-inferiority trials due to missing data, special 
attention will be paid to the handling of missing data in statistical analysis. Although, it 
is expected that the pattern of missing data will be similar in both treatment arms given 
that the treatment arms are the same drug but different formulations and it is expected 
that the impact of missing data on the primary endpoint to be minimal. Imputation 
under the non-inferiority null hypothesis [Koch, 2008] for all missing data for the 
primary analysis at Week 26 will be implemented.
9.4.5.2  Extent of Missing Primary Analysis Data
Missing data is expected to arise mainly from subjects missing complete visits. The 
amount of missing data for those baseline covariates included in the statistical analysis is 
expected to be none or at worst minimal. If it should occur, that subject will effectively 
be lost to analysis. Missing data for HbA1c between two non-missing visits will be 
considered missing at random (intermediate missing data).
In this study, subjects who withdraw from treatment will stay in the study. In the eCRF, 
the reason for treatment discontinuation and the reason for withdrawal from the study are 
collected separately. Whenever the HbA1c value at Week 26 is missing (end of the 
study), the reason can be determined based on available data in these two locations.
The reason for missing data can be classified as lost to follow-up or withdrawal of 
consent.
9.4.5.3  Reasons for Withdrawal
Reasons for withdrawal from the study are lost to follow-up or withdrawal consent.  All 
subjects who discontinuation from investigational product due to the reasons listed 
under Section 5.5 will remain in the study and efficacy and safety data will be 
collected.


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9.4.5.4  Handling of Missing Data
The impact of missing data will be explored, as outlined below, for the ITT Analysis 
Population only.
Examination of Missing Data Patterns
It is expected that the pattern of missing data will be similar in both treatment arms given 
that each treatment arm is using the same drug but different formula. 
To examine the nature of missing data, due to lost to follow-up or withdrawal consent,
cohorts of subjects will be defined based on the scheduled assessments (HbA1c change 
from baseline) that were completed at Weeks 1, 4, 8, 12, 16, 20, and 26.

Subjects who have week 1 assessment only

Subjects who have assessments up to and including Week 4 only

Subjects who have assessments up to and including Week 8 only

Subjects who have assessments up to and including Week 12 only

Subjects who have assessments up to and including Week 16 only

Subjects who have assessments up to and including Week 20 only

Subjects who have assessments up to and including Week 26.
The number and percentage of subjects on each treatment in the 7 cohorts defined here 
will be tabulated. Graphical methods will be used to examine changes from baseline over 
time to assess the pattern of outcomes prior to withdrawal.
Sensitivity Analyses 
The sensitivity of the results of analysis to the method of handling missing values will 
be investigated, especially if the number of missing values is substantial or if the 
characteristics of missing values differ between treatment groups. 
To assess the impact of subjects who discontinued investigational product and stayed in 
the study; exclusion of data after treatment discontinuation may also be performed if a 
significant number of subjects discontinue study medication prior to Week 26. On 
treatment data will be analyzed using MMRM model as described in Section 9.4.1.  
Week 26 observations off-treatment will be imputed under the non-inferiority null 
hypothesis [Koch, 2008].
Sensitivity analyses using a different type of multiple imputation method will be 
conducted. Firstly, missing data between two non-missing time points will be 
considered missing at random (MAR). The analyses using the last mean carried 
forward (LMCF) approach will be performed using the following rates of HbA1c 
increase: 0%/month, 0.1%/month, and 0.2%/month to explore the potential impact as 
in a tipping-point analysis. For each treatment group, these 3 rates will be assumed, 
resulting in 9 scenarios. The resulting treatment differences and associated P-values 
for non-inferiority will be tabulated against the varying rates of HbA1c increase. This 


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estimand is one where those who withdraw are assumed to revert to an unstable 
treatment regimen with an increasing rate of HbA1c. For each imputation data set, an 
analysis of variance will be carried using Week 26 data, both actual and imputed, 
using the same covariates as in the primary analysis. Contrasts of interest will be 
estimated and then combined across imputations using standard multiple imputation 
rules.

SAP_001.pdf: 
CONFIDENTIAL
The GlaxoSmithKline group of companies
200952
1
Division
:
Worldwide Development
Information Type
:
Reporting and Analysis Plan (RAP)
Title
:
Reporting and Analysis Plan for A Repeat-dose Study in 
Subjects with Type 2 Diabetes Mellitus to Assess the 
Efficacy, Safety, Tolerability and Pharmacodynamics, of 
Albiglutide Liquid Drug Product
Compound Number 
:
GSK716155
Effective Date 
:
14-JUL-2017
Description :

The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol 200952.

This RAP is intended to describe the planned efficacy (primary, secondary and 
exploratory) and safety analyses required for the study. 

This RAP will be provided to the study team members to convey the content of the
content of the final Statistical Analysis Complete (SAC) Deliverable.
Author’s Name and Functional Area: 
14-JUL-2017
Senior Biostatistician, PPD
Biostatistics Team Lead, PPD
Approved by: 
14-JUL-2017
Principal Statistician, Clinical Statistics, R&D Projects Clinical 
Platforms & Sciences, GlaxoSmithKline
Copyright 2017 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD
PPD


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TABLE OF CONTENTS
PAGE
1.
REPORTING & ANALYSIS PLAN SYNPOSIS.........................................................5
2.
SUMMARY OF KEY PROTOCOL INFORMATION ..................................................7
2.1.
Changes to the Protocol Defined Statistical Analysis Plan............................7
2.2.
Study Objective(s) and Endpoint(s)...............................................................7
2.3.
Study Design ................................................................................................9
2.3.1.
Overview of Study Design and Key Features.................................9
2.3.2.
Study Design ...............................................................................10
2.4.
Statistical Hypotheses.................................................................................10
3.
PLANNED ANALYSES ..........................................................................................11
3.1.
Interim Analyses .........................................................................................11
3.2.
Final Analyses ............................................................................................11
4.
ANALYSIS POPULATIONS ...................................................................................12
4.1.
Protocol Deviations.....................................................................................12
5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS.....................................................................................................14
6.
STUDY POPULATION ANALYSES .......................................................................15
6.1.
Overview of Planned Analyses ...................................................................15
6.2.
Disposition of Subjects................................................................................16
6.3.
Protocol Deviations.....................................................................................16
6.4.
Demographic and Baseline Characteristics.................................................16
6.5.
Exposure to Study Drug..............................................................................16
6.6.
Treatment Compliance................................................................................17
6.7.
Medications ................................................................................................17
6.8.
Medical History ...........................................................................................17
7.
PRIMARY STATISTICAL ANALYSES....................................................................19
7.1.
Efficacy Analyses........................................................................................19
7.1.1.
Overview of Planned Efficacy Analyses .......................................19
7.1.1.1.
Primary Analysis on Primary Efficacy Endpoint ..........19
7.1.1.2.
Supportive Analyses on Primary Efficacy 
Endpoint.....................................................................20
7.1.1.3.
Analyses on Primary Efficacy Endpoint by 
Subgroups..................................................................21
7.1.1.4.
Sensitivity Analysis.....................................................22
7.1.2.
Planned Efficacy Statistical Analyses...........................................23
8.
SECONDARY STATISTICAL ANALYSES .............................................................25
8.1.
Efficacy Analyses........................................................................................25
8.1.1.
Overview of Planned Efficacy Analyses .......................................25
8.1.1.1.
FPG Change from Baseline at Week 26 and 
over Time ...................................................................25
8.1.1.2.
HbA1c Change from Baseline over Time .....................25
8.2.
Safety and Tolerability Analyses .................................................................26
8.2.1.
Overview of Planned Analyses ....................................................26


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8.2.2.
Injection Site Reactions ...............................................................27
8.2.3.
Immunogenicity............................................................................27
8.2.4.
Adverse Events............................................................................28
8.2.4.1.
General Adverse Events Summaries..........................28
8.2.4.2.
Treatment Emergent Adverse Events.........................29
8.2.4.3.
Treatment-Related Adverse Events............................29
8.2.4.4.
Adverse Events by Maximum Intensity .......................29
8.2.4.5.
Most Common Adverse Events ..................................29
8.2.5.
Deaths and Serious Adverse Events............................................30
8.2.6.
Adverse Events Leading to Discontinuation of 
Investigational Product and/or Withdrawal from the Study ...........30
8.2.7.
Adverse Events of Special Interest ..............................................30
8.2.7.1.
Hypoglycemic Events .................................................30
8.2.7.2.
Cardiovascular Events................................................31
8.2.7.3.
Pancreatitis and Pancreatic Cancer............................31
8.2.7.4.
Thyroid Adverse Events .............................................31
8.2.7.5.
Gastrointestinal (GI) Events........................................31
8.2.7.6.
Systemic Allergic Reactions .......................................32
8.2.7.7.
Liver Events................................................................32
8.2.7.8.
Atrial Fibrillation/Flutter...............................................32
8.2.7.9.
Pneumonia .................................................................33
8.2.7.10.
Diabetic Retinopathy ..................................................33
8.2.7.11.
Appendicitis................................................................33
8.2.7.12.
Malignant Neoplasm...................................................33
8.2.8.
Pregnancies.................................................................................33
8.2.9.
Clinical Laboratory Evaluations....................................................33
8.2.9.1.
Chemistry, Hematology and Urinalysis .......................33
8.2.10.
Other Safety Measures................................................................34
8.2.10.1.
Vital Signs ..................................................................34
8.2.10.2.
Electrocardiograms.....................................................35
8.2.10.3.
Physical Exams..........................................................35
8.3.
Pharmacokinetic Analyses..........................................................................36
8.3.1.
Overview of Planned Analyses ....................................................36
8.4.
Pharmacogenetic data analyses .................................................................36
9.
OTHER STATISTICAL ANALYSES .......................................................................37
10. REFERENCES.......................................................................................................38
11. APPENDICES........................................................................................................39
11.1.
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population.....................................................................................40
11.1.1.
Exclusions from Per Protocol Population .....................................40
11.1.2.
Significant Protocol Deviation Rules ............................................40
11.2.
Appendix 2: Time & Events.........................................................................42
11.2.1.
Protocol Defined Time & Events ..................................................42
11.2.2.
Schedule of Assessments for Subjects Who Permanently 
Discontinue Investigational Product .............................................45
11.3.
Appendix 3: Assessment Windows .............................................................46
11.3.1.
Definitions of Baseline and Study Day .........................................46
11.3.2.
Visit Slotting Algorithm.................................................................46
11.3.3.
Multiple Evaluations.....................................................................47


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11.3.4.
Analysis Visit Windows ................................................................47
11.4.
Appendix 4: Treatment Periods...................................................................52
11.5.
Appendix 5: Derived and Transformed Data ...............................................53
11.5.1.
Change from Baseline .................................................................53
11.5.2.
Body Mass Index Calculation.......................................................53
11.5.3.
Total Person Time on Treatment .................................................53
11.5.4.
AE (Event) Density and Incidence Rate.......................................53
11.6.
Appendix 6: Premature Withdrawals & Handling of Missing Data ...............54
11.6.1.
Premature Withdrawal .................................................................54
11.6.2.
Missing Date Imputation ..............................................................54
11.6.3.
Handling of Missing Data.............................................................55
11.6.3.1.
Impact of Missing Data on Primary Endpoint ..............55
11.6.3.2.
Extent of Missing Primary Analysis Data ....................55
11.6.3.3.
Reasons for Withdrawal .............................................55
11.6.3.4.
Sensitivity Analysis Under Missing Not At 
Random (MNAR)........................................................55
11.6.3.5.
Sensitivity Analysis for Potential Data 
Fabrication .................................................................58
11.7.
Appendix 7: Values of Potential Clinical Importance ...................................59
11.7.1.
Laboratory ...................................................................................59
11.7.2.
Vital Signs....................................................................................61
11.7.3.
ECG.............................................................................................61
11.8.
Appendix 8: Multicenter Studies..................................................................63
11.8.1.
Definition of Geographic Region ..................................................63
11.9.
Appendix 9: Examination of Covariates, Subgroups & Other Strata............64
11.9.1.
Strata and Covariates ..................................................................64
11.9.2.
Examination of Subgroups...........................................................64
11.10. Appendix 10: Multiple Comparisons & Multiplicity .......................................65
11.10.1. Handling of Multiple Comparisons & Multiplicity...........................65
11.11. Appendix 11: Model Checking and Diagnostics for Statistical 
Analyses.....................................................................................................66
11.11.1. Model Checking and Diagnostics for Statistical Analyses ............66
11.12. Appendix 12: Sample Size Considerations .................................................68
11.12.1. Sample Size Assumptions ...........................................................68
11.12.2. Sample Size Sensitivity................................................................68
11.12.3. Sample Size Re-estimation or Adjustment...................................70
11.13. Appendix 13 – Abbreviations & Trade Marks ..............................................71
11.14. Appendix 14: List of Data Displays..............................................................74
11.14.1. Data Display Numbering..............................................................74
11.14.2. Study Population Tables..............................................................75
11.14.3. Efficacy Tables ............................................................................78
11.14.4. Efficacy Figures ...........................................................................81
11.14.5. Safety Tables...............................................................................83
11.14.6. Safety Figures .............................................................................89
11.14.7. ICH Listings .................................................................................91
11.14.8. Non-ICH Listings..........................................................................93


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1.
REPORTING & ANALYSIS PLAN SYNPOSIS
Overview
Key Elements of the RAP
Purpose

This study will evaluate the efficacy, safety, tolerability and pharmacodynamics 
(PD) response of albiglutide liquid drug product relative to the commercial 
lyophilized drug product in subjects with type 2 diabetes mellitus (T2DM) failing 
to achieve optimal glycemic control on their current regimen of diet and exercise 
or stable dose of metformin. Specifically, potential for immunogenicity (e.g. 
incidences of anti-drug antibodies [ADA]) and injection site reactions (ISRs) will 
be evaluated as part of the overall safety assessment in this study.
Protocol

This RAP is based on the protocol amendment [(Dated: 26/MAY/2016) of study 
GSK200952 (GSK Document No. : 2014N210004_02] and eCRF Version 2.
Primary 
Objective

To evaluate the efficacy of albiglutide liquid product as measured by glycated 
hemoglobin (HbA1c) change from baseline at Week 26.
Primary 
Endpoint

Change from baseline in HbA1c at Week 26
Study 
Design

This is a phase III, randomized, double-blind, multicenter, parallel-group, 
repeatdose, study of 26 weeks duration to evaluate the efficacy, safety, 
tolerability and PD response of albiglutide liquid drug product relative to the 
commercial lyophilized drug product in subjects with T2DM.

The study will recruit subjects with T2DM who are failing to achieve optimal 
glycemic control on their current regimen of diet and exercise or stable dose of 
metformin. Subjects will continue on their current regimen for the duration of 
their participation in the study.

This study will comprise 3 study periods: screening (2 weeks), treatment (26 
weeks) and for those subjects not entering the extension study a follow-up 
period (8 weeks).

At randomization, subjects will be stratified by age (<65 or ≥65 years of age), 
weight (<90 kg or ≥90 kg), and background antidiabetic therapy (diet and 
exercise or stable dose of metformin). Subjects will be randomized in a 1:1 ratio 
to either Albiglutide liquid drug product administered by an auto-injector or 
Albiglutide lyophilized drug product administered by a pen-injector.
Planned 
Analyses

Final Analysis: After all subjects have completed the planned 26 weeks of 
randomized study treatment and the subsequent follow-up phase if applicable, 
the final analysis for the clinical study report will be performed. At this time, the 
database will be frozen.
Analysis 
Populations

Intent-to-Treat (ITT) Population

Safety Population

Per-Protocol (PP) Population

Pharmacokinetics (PK) Population
Hypothesis

The primary hypothesis to be tested is that the liquid drug product will provide 


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Overview
Key Elements of the RAP
glycemic control (as measured by HbA1c change from baseline) non-inferior to 
the lyophilized drug product for a period of 26 weeks of treatment in subjects 
with T2DM.
Primary 
Analyses

The primary endpoint is the change from baseline in HbA1c at Week 26, which
will be analyzed using a mixed-effect model with repeated measures (MMRM) 
in the intent-to-treat (ITT) population. MMRM will use all available data from 
Week 4 up to Week 26 after hyperglycemia rescue and discontinuation from 
investigational product. Imputation under the non-inferiority null hypothesis for 
missing data will be incorporated. Multiple imputations will be used to replace 
missing data of change from baseline of HbA1c at Week 26 for all subjects in 
both treatment arms as a first step, and then to make all the imputed values for 
the liquid drug product arm worse by the non-inferiority margin 0.4. Non-
inferiority testing will be performed at a one-sided alpha of 0.025 and non-
inferiority margin of 0.4%.
Secondary 
Analyses

The evaluation of the safety and tolerability as assessed by immunogenicity and 
ISRs of albiglutide liquid drug product and the lyophilized drug product will be 
provided by reporting the event rates, and the associated 95% CI.

The overall general safety and tolerability of albiglutide liquid drug product 
versus lyophilized drug product will be evaluated in tabular and/or graphical 
format and summarized descriptively.

The secondary endpoint Fasting Plasma Glucose (FPG) change from baseline 
at Week 26 will be analyzed using MMRM without imputation.

To assess the PD effect of albiglutide over time for the secondary endpoints 
change from baseline in HbA1c and in FPG over time; MMRM models without 
imputation will be used.

Pharmacokinetics (PK) trough plasma concentration data will be summarized 
by treatment. No formal statistical analyses will be conducted.


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2.
SUMMARY OF KEY PROTOCOL INFORMATION
2.1.
Changes to the Protocol Defined Statistical Analysis Plan
Any changes from the planned statistical analysis specified in the protocol
amendment 2 (Dated: 26/MAY/2016) are outlined below.

Primary and supportive analyses:
o
Protocol specified “The MMRM model via PROC MIXED will 
include HbA1c change from baseline at post-baseline scheduled
visits up to Week 26 as dependent variables; treatment, region, age 
category, weight category, background antidiabetic therapy, visit 
week and treatment-by-week interaction; baseline HbA1c as a 
continuous covariate; and subject as a random effect”.
o
Changes in the Reporting & Analysis Plan:

Week 1 visit is excluded from the MMRM due to small or 
zero change in HbA1c expected at Week 1 and the primary 
endpoint is change from baseline inHbA1c at Week 26. 
Inclusion of this visit in the MMRM model does not add 
much statistical efficiency, instead it likely leads to a non-
positive definite estimated variance matrix and thus 
unstable estimate of treatment effect.

Baseline HbA1c-by-week interaction is added in the 
MMRM to allow for a more appropriate model fit by 
accounting for different coefficients of baseline at each 
post-baseline visit (Week 4, 8, 12, 16, 20 and 26) and thus 
avoid potential convergence issue due to insufficient model 
specification.
2.2.
Study Objective(s) and Endpoint(s)
Objectives
Endpoints
Primary Objectives
Primary Endpoints

To evaluate the efficacy of 
albiglutide liquid product as 
measured by glycated hemoglobin 
(HbA1c) change from baseline at 
Week 26.

Change from baseline in HbA1c at Week26
Secondary Objectives
Secondary Endpoints

To assess safety and tolerability 
of albiglutide specifically 
immunogenicity and ISRs.

Adverse events (AEs) and serious AEs (SAEs), 
physical examinations, clinical laboratory 
evaluations, vital signs, and 12-lead 
electrocardiograms (ECGs).


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Objectives
Endpoints

Anti-albiglutide antibody production and rates of 
ISRs over time.

To evaluate the PD effect of 
albiglutide on fasting plasma 
glucose (FPG) change from 
baseline at Week 26.

Change from baseline in FPG at Week 26

To assess the PD effect of 
albiglutide over time

Change from baseline in HbA1c over time

Change from baseline in FPG over time

To evaluate trough PK 
concentrations of albiglutide 
following repeat dosing

Trough concentrations of albiglutide


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2.3.
Study Design
2.3.1.
Overview of Study Design and Key Features
Overview of Study Design and Key Features
Design
Features

Randomized, double-blind, multicenter, parallel-group, repeat-dose study of 
26 weeks duration
Dosing

During the treatment period study treatment will be administered once weekly 
by subcutaneous (s.c.) injection in the abdomen, thigh, or upper arm. 

Study personnel will administer study treatment at clinic visits.

Subjects will receive 30 mg of albiglutide for 4 weeks and will then be up-
titrated to 50 mg albiglutide for the remaining 22 weeks of the study.

Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT 
permitted. If a subject experiences tolerability issues with the 50 mg dose then 
the subject may be withdrawn from the study at the discretion of investigator.
Treatment 
Assignment

Randomized treatment assignment will be done via the Interactive Voice 
Response System (IVRS) and randomization will be implemented based on a 
sequestered fixed randomization schedule. 

Approximately 300 subjects will be randomized for this study. Eligible subjects 
will be stratified by age (<65 or ≥65 years of age), weight (<90 kg or ≥90 kg), 
and background antidiabetic therapy (diet and exercise or stable dose of 
metformin). Subjects will be randomized in a 1:1 ratio to either: 1. Albiglutide 
active liquid auto-injector + placebo lyophilized DCC pen injector; or, 2. 
Albiglutide active lyophilized DCC pen injector + placebo liquid auto-injector.
Interim 
Analysis

No interim analysis is planned for this study.


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2.3.2.
Study Design
This is a phase III, randomized, double-blind, multicenter, parallel-group, repeatdose, 
study of 26 weeks duration to evaluate the efficacy, safety, tolerability and PD response 
of albiglutide liquid drug product relative to the commercial lyophilized drug product.
This study will comprise 3 study periods: screening (2 weeks), treatment (26 weeks) and 
for those subjects not entering the extension study a follow-up period (8 weeks).
The study will recruit subjects with T2DM who are failing to achieve optimal glycemic 
control on their current regimen of diet and exercise or stable dose of metformin. 
Subjects will continue on their current regimen for the duration of their participation in 
the study.
During the screening period, subjects will provide written informed consent and undergo 
procedures to determine eligibility for study participation. Screening will occur within 2 
weeks of randomization.
At randomization, subjects will be stratified by age (<65 or ≥65 years of age), weight 
(<90 kg or ≥90 kg), and background antidiabetic therapy (diet and exercise or stable dose 
of metformin). Subjects will be randomized in a 1:1 ratio to either:

Albiglutide active liquid auto-injector + placebo lyophilized DCC pen injector;
or,

Albiglutide active lyophilized DCC pen injector + placebo liquid auto-injector.
Study treatment will be administered once weekly by s.c. injection in the abdomen, thigh, 
or upper arm. Study personnel will administer study treatment at clinic visits. Subjects 
will receive 30 mg of albiglutide for 4 weeks and will then be up-titrated to 50 mg 
albiglutide for the remaining 22 weeks of the study. Down-titration (dose reduction) of 
albiglutide from 50 mg to 30 mg is NOT permitted. If a subject experiences tolerability 
issues with the higher 50mg dose then the subject may discontinue investigational 
product (at the discretion of the investigator) and will be followed for safety and efficacy.
Subjects who completed the 26 week treatment period, did not discontinue investigational 
product, and meet all eligibility criteria may consent to participate in Study 204682, a 26 
week extension study.
2.4.
Statistical Hypotheses
The primary hypothesis to be tested is that the liquid drug product will provide glycemic 
control (as measured by HbA1c change from baseline) non-inferior to the lyophilized 
drug product for a period of 26 weeks of treatment in subjects with T2DM.

The null hypothesis is that the difference in the mean change from baseline to 
Week 26 in HbA1c between the liquid drug product and the lyophilized drug 
product is greater than the non-inferiority margin of 0.4%. 


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
The alternative hypothesis is that the difference in the mean change from Baseline 
to Week 26 in HbA1c between the liquid drug product and the lyophilized drug 
product is less than or equal to the non-inferiority margin of 0.4%.

The null hypothesis will be tested based on the upper bound of 1-sided 97.5% 
confidence interval (equivalently, the upper bound of a 2-sided 95% confidence 
interval) of the least squares mean of the treatment difference estimated from a 
MMRM model. The MMRM model will include HbA1c change from baseline as 
the dependent variable; treatment, region (defined in Appendix 8: Multicenter), 
age category (<65 or >=65 years), weight category (<90 or >=90 kg), background 
antidiabetic therapy (diet and exercise or stable dose of metformin), visit week, 
treatment-by-week interaction and baseline HbA1c-by-week interaction as fixed 
effects; baseline HbA1c as a continuous covariate; and subject as a random effect.
An unstructured covariance matrix will be used for the MMRM analysis, unless 
the model does not converge, in which case the covariance matrix will be decided 
upon model convergence status and the Akaike information criterion. If the upper 
bound of 1-sided 97.5% confidence interval is less than or equal to 0.4%, non-
inferiority will be concluded.
3.
PLANNED ANALYSES
3.1.
Interim Analyses
No interim analysis is planned for this study.
3.2.
Final Analyses
The final planned primary analyses will be performed after the completion of the 
following sequential steps:
1.
All subjects have completed the planned 26 weeks of study treatment or have 
completed participation in the study and the subsequent follow-up phase if 
applicable. For subjects who did not enter the extension study (Study 204682), they 
should complete the follow-up phase.
2.
All required database cleaning activities have been completed and final database 
release and database freeze has been declared.
3.
All criteria for unblinding the randomization codes have been met. 


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4.
ANALYSIS POPULATIONS
Population
Definition / Criteria
Analyses Evaluated
Intent-To-Treat

Comprise of all randomized subjects who 
receive at least one dose of study treatment
and have a baseline assessment.

This population will be analysed according to
randomly assigned treatment

Efficacy
Safety

Comprise of all enrolled subjects who receive 
at least one dose of study treatment.

This population will be analysed according to 
the treatment the subject actually received.

Safety
Per-Protocol

Comprise of all randomized subjects who 
complete study procedures through Week 26 
and are compliant with the protocol.

This population will be analysed according to 
randomly assigned treatment.

Protocol deviations that would exclude 
subjects from the PP population are defined in 
Section 4.1 (Protocol Deviations) and 
Appendix 1 (Protocol Deviation Management 
and Definition for Per-Protocol Population).

Supportive analyses 
of the efficacy 
endpoints
Pharmacokinetic

Subjects in the Safety population for 
whom a pharmacokinetic sample is
obtained and analysed.

PK
NOTES : 

Please refer to Appendix 14 List of Data Displays which details the population to be used for each 
displays being generated.
4.1.
Protocol Deviations

Significant protocol deviations (including deviations related to study 
inclusion/exclusion criteria, conduct of the trial, subject management or subject
assessment) will be summarised by category and standard text description.

Per-Protocol population is defined as all randomized subjects randomly assigned to 
treatment who complete study procedures on treatment through Week 26 and are 
compliant with the protocol. Significant deviations which result in exclusion from 
the Per-Protocol population will also be listed. (Please refer to Appendix 1: Protocol 
Deviation Management and Definitions for Per Protocol Population).

Protocol deviations will be tracked by the study team throughout the conduct of the 
study in accordance with the Study Deviation Rules document.


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o
Data will be reviewed prior to unblinding and freezing the database to ensure all 
significant deviations which may lead to exclusion from the Per-Protocol 
population are captured and categorised on the protocol deviations dataset. 
o
This dataset will be the basis for the summaries and/or listings of protocol 
deviations.

All protocol deviations regardless of significance will be listed.

A separate summary and listing of all inclusion/exclusion criteria deviations will also 
be provided. This summary will be based on data as recorded on the 
inclusion/exclusion page of the eCRF.


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5.
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS
The primary analysis in this study is comparison between the treatment groups on the 
primary efficacy endpoint change from baseline in HbA1c with MMRM, where missing 
data at Week 26 will be imputed. For the lyophilized drug product arm the imputation 
will be based on assumption of the missing at random (MAR) while for the liquid drug 
product arm the imputation will be performed assuming the worsening of 0.4 relative to 
what would be expected under MAR. Missing data handling and sensitivity analysis
under different assumptions of missing mechanism for the primary endpoint can be found 
in Appendix 6: Premature Withdrawals & Handling of Missing Data.
In the conduct of the study, specific measures will be put in place to prevent and 
minimize missing data due to treatment withdrawals, noncompliance, etc. Upon study 
completion, the characteristics (frequency, causes) of the missing data, especially as 
related to the key efficacy endpoints, will be examined to inform the sensitivity analysis 
and imputation methods concerning missing data.
Table 1 provides an overview of appendices within the RAP for outlining general 
considerations for data analyses and data handling conventions. 
Table 1
Overview of Appendices
Section
Component
11.1
Appendix 1: Protocol Deviation Management Plan and Definitions for Per-Protocol 
Population
11.2
Appendix 2: Time & Events
11.3
Appendix 3: Assessment Windows
11.4
Appendix 4: Treatment Periods
11.5
Appendix 5: Derived and Transformed Data
11.6
Appendix 6: Premature Withdrawals & Handling of Missing Data
11.7
Appendix 7: Values of Potential Clinical Importance
11.8
Appendix 8: Multicenter Studies
11.9
Appendix 9: Examination of Covariates, Subgroups & Other Strata
11.10
Appendix 10: Multiple Comparisons & Multiplicity
11.11
Appendix 11: Model Checking and Diagnostics for Statistical Analyses
11.12
Appendix 12: Sample Size Considerations
11.13
Appendix 13: Abbreviations and Trademarks
11.14
Appendix 14: List of Data Displays


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6.
STUDY POPULATION ANALYSES
6.1.
Overview of Planned Analyses
Table 2Table 2
provides an overview of the planned study population analyses,
with full details of data displays being presented in Appendix 14: List of Data Displays.
Table 2
Overview of Planned Study Population Analyses
Display Type
Data Display’s Generated
Figure
Table
Listing
Randomization
Randomization
Y
Subject Disposition
Subject Disposition
Y
Y
Reasons for Screening Failures
Y
Y
Reasons for Withdrawal from Study
Y
Y
Reasons for Discontinuing Study Treatment
Y
Y
Protocol Deviations
Y
Y
Deviations Leading to Exclusions from PP Population
Y
Y
Inclusion and Exclusion Criteria Deviations
Y
Y
Demography and Baseline Characteristics
Demographics and Baseline Characteristics
Y
Y
Race & Racial Combinations
Y
Y
Substance use
Y
Y
Medical Condition & Concomitant  Medications
Medical Conditions (Current/Past)
Y
Y
Concomitant Medication
Y
Y
Exposure and Treatment Compliance
Exposure to Study Drug
Y
Y
Treatment Compliance
Y
Y
Note: additional tables, listings and figures will be provided in Appendix 14: List of Data Displays.

Y = Yes display generated.
Following review of the data, additional analyses maybe conducted to further support the 
evaluation and interpretation of the data.


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6.2.
Disposition of Subjects
The number of subjects who were randomized and the number of subjects within each 
population (ITT, Safety, PP, PK) will be summarized for each treatment group. A 
summary of subjects randomized by geographic region, and site will also be provided by 
treatment group. 
The numbers and percentages of subjects who completed the study, discontinued the 
study, and discontinued the study treatment, along with reasons for discontinuation, will 
be summarized by treatment group. Additionally, among subjects who completed the 
study the number and percentage of subjects who continued into the open-label extension 
study, and did not participate in the open-label extension study will be also summarized 
and tabulated.
Subject status by visit summary will be provided. 
Subject disposition data will be listed as well. All disposition summaries will be based on 
the all randomized subjects.
6.3.
Protocol Deviations
As described in Section 4.1, all significant protocol deviations, those leading to exclusion 
from PP population, and all inclusion/exclusion criteria deviations will be summarized 
and listed, separately.
6.4.
Demographic and Baseline Characteristics
Continuous variables such as age, body mass index, weight, and height will be 
summarized using descriptive statistics (n, mean, standard deviation, and median, 
minimum, maximum). Categorical variables including age group (<65, 65 years), sex, 
race, ethnicity, baseline weight category (<90 kg or ≥90 kg), and background antidiabetic 
therapy (diet and exercise or stable dose of metformin) will be summarized using 
numbers and percentages. Summaries will be presented by treatment group using the 
safety population. 
Summary of substance (alcohol and tobacco) use will be provided, as well as a by-subject 
listing of data on alcohol and tobacco use. All summaries will be performed using the 
safety population.
6.5.
Exposure to Study Drug
Descriptive statistics including the number of subjects, mean, standard deviation, median, 
minimum, and maximum for the duration of exposure to study drug will be presented by 
treatment group for the safety population. The duration of study drug exposure (in days)
is defined as date of last dose of study drug - date of first dose of study drug + 1; missing 
doses will be ignored in this calculation. The total person time on study drug (in years) as 
defined in Appendix 5 will also be displayed for each treatment group. 
A by-subject listing of study drug administration will also be presented.


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6.6.
Treatment Compliance
Study treatment (both active drug and placebo injector) will be administered to the 
subject by the site personnel in the clinic at each scheduled weekly visit from Week 0 
(i.e. Baseline/Randomization), Week 1 through Week 25. At each scheduled weekly visit, 
study treatment administration status (Yes/No), date/time of dose administered (if Yes) 
and reason no dose administered (if No) will be recorded in the Exposure eCRF page. 
Treatment compliance (in percentage) will be based on the Exposure eCRF page and 
calculated as total number of doses administered divided by total number of doses 
expected over all available scheduled visits on treatment. Treatment compliance will be 
summarized for all subjects, as well as for subjects who discontinue study treatment early 
and subjects who complete study treatment. Treatment compliance will be also 
categorized as < 80% and >=80%, and summarized descriptively by treatment group.
Individual subject compliance information will also be listed. All summaries will be 
performed using the safety population.
Acceptable overall compliance for IP (albiglutide liquid and lyophilized) in this study 
will be ≥80%. 
6.7.
Medications
Any prior and concomitant medication used during the study will be recorded and coded 
using GSKDrug Dictionary, which will be updated whenever available throughout the 
life of the study. Summary of all medications by treatment group and preferred term will 
be provided in relation to treatment phase (prior medication, concomitant medication, or 
post-therapy medication). Prior medications are those started and stopped before the first 
dose of randomized study drug. Concomitant medications are those taken at any time on 
or after the day of the first dose of randomized study drug and within 25 days after the 
last dose of randomized study drug, including those medications that started prior to 
randomization and continued into the treatment period. Post-therapy medications are 
those taken more than 25 days after the day of the last dose of randomized study drug. 
All prior and concomitant medications will be listed using generic and verbatim terms. 
All summaries will be performed using the safety population.
6.8.
Medical History
Subject data listings and summary tables will be provided for the following current 
and/or past conditions:

cardiovascular medical history

diabetes related medical history

medical/surgical procedure history

gastrointestinal (GI) medical history

cancer history


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
pneumonia medical history

skin medical conditions

thyroid medical history, thyroid cancer history, benign thyroid medical conditions

thyroid cancer family history

pancreatitis family history

pancreatic cancer family history

other medical history

other medical/surgical surgery
The number and percentage of subjects with current and/or past medical histories listed 
above will be reported by treatment group. A summary of duration of diabetes disease 
history in years will be provided. The duration of diabetes disease history is calculated as 
the years lapsed between screening visit date and T2DM diagnosis date. 
In addition, by subject listings of medical and family history status and all the medical 
conditions listed above will be provided. 
All summaries will be performed using the safety population. 


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7.
PRIMARY STATISTICAL ANALYSES
7.1.
Efficacy Analyses
7.1.1.
Overview of Planned Efficacy Analyses
The primary efficacy analyses will be based on the ITT population, unless otherwise 
specified.
Table 3 provides an overview of the planned efficacy analyses, with full details of data 
displays being presented in Appendix 14: List of Data Displays.
Table 3
Overview of Planned Efficacy Analyses
Endpoint/Parameter/
Display Type
Absolute
Change from Baseline
Stats Analysis
Summary
Individual
Stats Analysis
Summary
Individual
T
F
L
T
F
F
L
T
F
L
T
F
F
L
HbA1c at Week 26
Y
Y
Y
Y
Y
Y
Y
Y
NOTES :

T = Table, F = Figure, L = Listing, Y = Yes display generated.

Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
Following review of the data, additional analyses maybe conducted to further support the 
evaluation and interpretation of the data.
7.1.1.1.
Primary Analysis on Primary Efficacy Endpoint
The primary endpoint is the change from baseline in HbA1c at Week 26. The primary 
analysis of the primary endpoint will be conducted using a mixed-effect model with 
repeated measures (MMRM) in the ITT Population. The primary analysis will include all 
HbA1c values collected at scheduled visits from Week 4 up to Week 26. This will 
include values after hyperglycemia rescue and discontinuation from investigational 
product. Imputation under the non-inferiority null hypothesis for missing data will be 
incorporated [Koch, 2008]. Multiple imputation assuming missing at random (MAR) will 
be used to replace missing data of change from baseline of HbA1c at Week 26 for all 
subjects in both treatment arms as a first step, and then to make all the imputed values for 
the liquid drug product arm worse by the non-inferiority margin 0.4. 
Multiple imputation approach under MAR uses separate means and variance-covariance 
parameter estimation for each treatment arm (Carpenter and Kenward, 2013). Missing 
values for each subject will be imputed multiple times based on his or her own observed 
HbA1c change from baseline values available and also based on the estimated means and 
variance-covariance from the treatment group where that subject is randomized to. This 
approach will be used for all missing data at Week 26 due to any reason including, but 
not limited to lost to follow-up and withdrawl consent. The details of implementing this 
multiple imputation approach are the following:


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
Step 1a: Missing values at Week 26 will be imputed 100 times via SAS PROC 
MI (specifying BY treatment group, using MCMC statement with the option 
chain = multiple, including baseline and all post-baseline scheduled visits up to 
Week 26). As a result, 100 imputed datasets will be generated. Note: Only 
imputed values at Week 26 will be retained while the imputed values at other 
visits will be dropped from the imputed datasets.

Step 1b: For each of the 100 imputed datasets from Step 1 the imputed values at 
Week 26 for the liquid drug product arm will be increased by 0.4.

Step 2: Apply MMRM analysis as specified below for each of the 100 imputed 
dataset and save LSmeans (standard error) for each treatment arm at Week 26 and 
difference in LSmeans between treatment groups (standard error) from each of the 
100 analyses. 

Step 3: Combine the 100 set of analysis results using Rubin's rules (Rubin, 1987) 
via SAS PROC MIANALYZE. The treatment differences, confidence intervals 
and p-values will be estimated by MODELEFFECTS and STDERR statement. 
Use the degrees of freedom (EDF) you would have if the dataset were complete.
The MMRM model via PROC MIXED will include HbA1c change from baseline at post-
baseline scheduled visits from Week 4 up to Week 26 as dependent variables; treatment, 
region (defined in Appendix 8: Multicenter), age category (<65 or >=65 years), weight
category (<90 or >=90 kg), background antidiabetic therapy (diet and exercise or stable 
dose of metformin), visit week, treatment-by-week interaction and baseline HbA1c-by-
week interaction as fixed effects; baseline HbA1c as a continuous covariate; and subject 
as a random effect. An unstructured covariance matrix will be used for the MMRM 
analysis, unless the model does not converge, in which case the covariance matrix will be 
decided upon model convergence status and the Akaike information criterion. Treatment 
effects estimates (and associated CI) of albiglutide liquid drug product will be evaluated 
within this MMRM model as least squares means contrasts relative to the lyophilized 
drug product. 
The null hypothesis will be tested based on the 1-sided 97.5% confidence interval (with 
upper bound, equal to that of 2-sided 95% confidence interval) of the treatment difference 
at Week 26, which is estimated from the multiple imputation/MMRM (i.e. combined 
MMRM results from multiple imputation). If the upper bound of the confidence interval 
is less than or equal to 0.4%, non-inferiority will be concluded.
In addition, the observed HbA1c and change from baseline HbA1c will be summarized 
descriptively and presented graphically.
7.1.1.2.
Supportive Analyses on Primary Efficacy Endpoint

Supportive analysis 1:
The primary endpoint change from baseline in HbA1c at Week 26 will be 
analysed using the same MMRM model as described in Section 7.1.1.1 but 
missing data are not explicitly imputed in this supportive analysis; although, there 


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is an underlying assumption that data is missing at random. All available 
scheduled post-baseline assessments from Week 4 up to Week 26 are utilized and, 
via modelling of the within subject correlation structure, the derived treatment 
difference at Week 26 is adjusted to take into account missing data. The MMRM 
analysis (using saturated fixed effects and an unstructured variance-covariance
matrix) is considered appropriate as the supportive analyses, as it has been shown 
to give sensible answers to on-treatment questions in a range of practical 
situations [Siddiqui,2009].
The least squares means (and standard errors) of change from baseline in HbA1c at 
Week 26 will be presented from the MMRM model. The least squares mean and 
the associated 1-sided 97.5% confidence interval (with upper bound, equal to that 
of 2-sided 95% confidence interval) of the treatment difference in change from 
baseline in HbA1c will be reported at Week 26. 

Supportive analysis 2: 
Analysis excluding HbA1c data after hyperglycaemia rescue and discontinuation 
from study treatment will also be performed as supportive. It is not expected to 
have a substantial number of subjects who will require rescue and/or discontinue 
from study treatment and that number of subjects would be similar for both 
treatment arms. However, rescue medications given to subjects in this study may 
distort the estimates of the underlying treatment effect when HbA1c change from 
baseline values at Week 26 are associated with rescue medications. To assess the 
impact of rescue and pure drug effect, analysis of pre-rescue data will be 
performed. The MMRM model will be similar to the one as described in Section 
7.1.1.1. Results of this analysis at Week 26 will supplement the primary analysis. 
No imputation will be conducted for this supportive analysis.

Supportive analysis 3:
The primary endpoint HbA1c change from baseline at Week 26 will be analyzed
using the same MMRM model as described in Section 7.1.1.1 in the PP 
population as a supportive analysis. No imputation will be conducted for this 
supportive analysis.
7.1.1.3.
Analyses on Primary Efficacy Endpoint by Subgroups
The primary endpoint HbA1c change from baseline at Week 26 will be examined by the 
following subgroups (also see Appendix 9) using the same multiple imputation/MMRM 
model approach for the primary analysis but also includes the subgroup- by-treatment-by-
visit interaction term (as well as subgroup-by-treatment and subgroup-by-visit interaction 
terms) in the MMRM model step. The adjusted mean difference between treatment 
groups and associated 95% confidence interval for each level of the subgroup will be 
estimated from the combined MMRM results from the multiple imputations.

Baseline HbA1c category (< 8% or >=8%)


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
Region (USA – North, USA – South Atlantic, USA – South Central and USA -
West)

Age category (<65 or >=65 years)

Weight category (<90 or >=90 kg)

Background antidiabetic therapy (diet and exercise or stable dose of metformin)

Gender (male or female)

Race (white or non-white)

Ethnicity (Hispanic or non-hispanic)

Duration of diabetes category (<5, 5 to 10 or >10 years) 
7.1.1.4.
Sensitivity Analysis
Sensitivity analyses will be performed for the primary efficacy endpoint to assess the 
robustness of the primary efficacy analysis results with respect to different methods of 
handling missing values. Detailed methodology is provided in Appendix 6: Premature 
Withdrawals & Handling of Missing Data.


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7.1.2.
Planned Efficacy Statistical Analyses
Primary Statistical Analyses
Endpoint(s)

Change from baseline in HbA1c at Week26
Model Specification

Multiple imputation: Use PROC MI by specifying BY treatment group, using MCMC statement 
with the option chain = multiple and including baseline and all post-baseline scheduled visits up 
to Week 26. Then the imputed values at Week 26 for the liquid drug product arm will be 
replaced with the originally imputed values plus 0.4.

MMRM model: Change from Baseline in HbA1c = Baseline HbA1c + Treatment + Region + Age 
Category + Weight Category + Background Antidiabetic Therapy + Visit Week + Treatment-by-
Visit Interaction + Baseline HbA1c-by-Visit Interaction. This model will be including all HbA1c 
values collected at scheduled visits from Week 4 up to Week 26 and will be performed for each 
imputation.

Combining analysis results: Use PROC MIANALYZE by applying the MODELEFFECTS and 
STDERR statement. The treatment differences, confidence intervals and p-values will be 
estimated by combining the multiple sets of MMRM results..
Model Checking & Diagnostics

Refer to Appendix 11: Model Checking and Diagnostics for Statistical Analyses.
Model Results Presentation

The treatment difference at Week 26 and its 1-sided 97.5% confidence interval (or equivalently
2-sided 95% confidence interval) estimated from the combined MMRM results from multiple 
imputation. 

Descriptive statistics for the observed HbA1c and change from Baseline HbA1c

Refer to Appendix 14 List of Data Displays
Supportive Statistical Analysis

The primary endpoint will also be analyzed using the MMRM model above including all HbA1c 
values collected at scheduled visits from Week 4 up to Week 26. This would include values 
after post-hyperglycemia rescue and discontinuation from investigational product. No explicit 
data imputation will be performed.

The primary endpoint will also be analyzed using the MMRM model above excluding post-
hyperglycemia rescue data and post discontinuation from study treatment data. No data 
imputation will be performed.

The primary endpoint will also be analyzed using MMRM model above in the Per-Protocol 
Population. No data imputation will be performed.
Model Specification

Same MMRM model as for the primary analysis
By-Subgroup Statistical Analysis

The subgroup analyses will be performed using the same multiple imputation/MMRM model
approach except in the MMRM step a treatment by subgroup interaction term is added to the 
model. The subgroups include baseline HbA1c category, region, age category (<65 or >=65 
years), weight category (<90 or >=90 kg), background antidiabetic therapy (diet and exercise 
or stable dose of metformin), gender, race, ethnicity and duration of diabetes category.

Refer to Appendix 9: Examination of Covariates, Subgroups & Other Strata.


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Model Specification

Change from Baseline in HbA1c = Baseline HbA1c + Treatment + Region + Age Category + 
Weight Category + Background Antidiabetic Therapy + Visit Week + Treatment-by-Visit + 
Baseline HbA1c-by-Visit Interaction + Subgroup (if not already in the model) + Subgroup-by-
Treatment+ Subgroup-by-Visit + Subgroup-by-Treatment-by-Visit.

Refer to Appendix 11: Model Checking and Diagnostics for Statistical Analyses for SAS code
Sensitivity Statistical Analysis

Refer to Appendix 6 Section 11.6.3.4: Sensitivity Analysis Under Missing Not At Random 
(MNAR)


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8.
SECONDARY STATISTICAL ANALYSES
8.1.
Efficacy Analyses
8.1.1.
Overview of Planned Efficacy Analyses
The secondary efficacy analyses will be based on the ITT population.
Table 4 provides an overview of the planned efficacy analyses, with further details of 
data displays being presented in Appendix 14: List of Data Displays.
Table 4
Overview of Planned Efficacy Analyses
Endpoint / Display Type
Stats Analysis
Summary
Individual
T
F
L
T
F
F
L
Change from baseline in FPG at Week 26
Y
Y
Y
Y
Y
Change from baseline in HbA1c over time
Y
Y
Y
Y
Y
Change from baseline in FPG over time
Y
Y
Y
Y
Y
NOTES :

T = Table, F = Figure, L = Listing, Y = Yes display generated.

Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
8.1.1.1.
FPG Change from Baseline at Week 26 and over Time
FPG change from Baseline by visit will be analyzed using the similar MMRM model as 
described in Section 7.1.1.1 with FPG replacing HbA1c in the model without imputation. 
The observed FPG and change from Baseline FPG will be summarized descriptively and 
presented graphically. The least squares means (and standard errors) of change from 
Baseline FPG will be plotted by treatment group. The analyses will be performed on ITT 
population and all data will be listed. 
8.1.1.2.
HbA1c Change from Baseline over Time
HbA1c change from baseline by visit will be analyzed using the same MMRM model as 
described in Section 7.1.1.1 without imputation in the ITT population. The observed 
HbA1c and change from baseline HbA1c will be summarized descriptively and presented 
graphically. The least squares means (and standard errors) of change from Baseline 
HbA1c will be plotted by treatment group.


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8.2.
Safety and Tolerability Analyses
8.2.1.
Overview of Planned Analyses
The safety analyses will be based on the safety population.
Safety and exposure for subjects continuing in extension study 204682 will be 
summarized too.
Table 5 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 14: List of Data Displays.
Table 5
Overview of Planned Safety Analyses
Endpoints
Observed
Change from 
Baseline
Summary
Individual
Summary
Individual
T
F
F
L
T
F
F
L
Injection Site Reaction
Y
Y
Immunogenicity
Y
Y
Adverse Events
  All AEs
Y
Y
  Pre-therapy, On-therapy, and Post-therapy AEs
Y
Y
  Relationship of AEs to Study Drug
Y
Y
  AEs by Maximum Intensity
Y
Y
  Most Common AEs
Y
Y
  Serious AEs
Y
Y
AEs and SAEs Leading to Treatment Discontinuation
Y
Y
  Fatal AEs and non-fatal SAEs
Y
Y
  AEs of special interest 
Y
Y
Incidence of hypoglycemic events (in total and by each 
category as defined by the American Diabetes 
Association criteria)
Y
Clinical Laboratory
Y
Y
Y
Y
Y
Y
Vital Signs
Y
Y
Y
Y
Y
Y
Electrocardiogram (ECG)
Y
Y
Y
Y
Y
NOTES :

T = Table, F = Figure, L = Listing, Y = Yes display generated.

Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.


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Following review of the data, additional analyses maybe conducted to further support the 
evaluation and interpretation of the data.
8.2.2.
Injection Site Reactions
Injection site reactions are reported by the investigators on the eCRF. The number and 
percentage of subjects with injection site reactions and 95% confidence intervals of the 
proportions will be presented by treatment group. In addition, the time to first occurrence 
of an injection site reaction will be analyzed and presented in a manner identical to that 
described for the first occurrence of a GI event in Section 8.2.7.5.
The number and percentage of subjects reporting injection site reactions at each study 
week will be presented by treatment group. Each week will include those subjects with 
the onset of an injection site reaction during that particular week as well as those subjects 
with injection site reactions from previous weeks that have not resolved. The incidence of 
injection site reactions will be plotted over time. Various characteristics of injection site 
reactions at the event level and subject level will be summarized.
A by-subject listing of injection site reactions will also be produced.
8.2.3.
Immunogenicity 
Serum for antidrug antibody testing will be obtained from all subjects before 
administration of study treatment at Week 0, 2, 4, 8, 12, 16, 20, 24, 26/early withdrawal 
and at follow-up (if applicable), according to the Time and Events Table in Appendix 2. 
The presence of anti-albiglutide antibodies will be assessed using a validated 
enzymelinked immunosorbent assay. The assay involves screening, confirmation, and 
titration steps (tiered-testing approach). Confirmed positive samples will be titrated to 
obtain the titre of antibodies and tested for GLP-1 and albumin cross-reactivity, as well as 
for albiglutide neutralizing activity. Samples positive for both anti-GLP-1 antibodies and 
drug neutralizing antibodies may be tested for GLP-1 neutralizing activity.
Anti-albiglutide antibody results will be analyzed by treatment arm, visit, and study 
period for the safety population. For subjects with positive anti-albiglutide antibody 
results, the number and percentage with positive albiglutide neutralizing antibody results, 
positive anti-GLP-1 antibody results, and positive anti-albumin antibody results will be 
provided separately at each assessment. The 95% confidence intervals for the proportions 
of the positive immunogenicity results will be calculated using exact binomial method, 
assuming a simple binomial distribution. Antibody titers will be summarized using 
descriptive statistics. Individual immunogenicity data, including antibody titers, will be 
listed for each subject.
Additionally, in the case of severe allergic reactions that include anaphylaxis, 
angioedema, or other severe potential hypersensitivity reactions, three 1-mL serum 
samples should be obtained for immunogenicity testing (within 24 hours of the event if 
possible) and sent to the central laboratory for immediate distribution to a contracted 
testing facility for specific immunological testing (albiglutide specific IgE and other tests, 


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as appropriate) A follow-up serum sample will be collected 8 weeks after the final dose 
of study treatment in the case of early withdrawal from the study. For subjects who have 
discontinued study treatment or subjects who have completed the 26 week treatment 
period, but do not consent and/or are not eligible to participate in the 26 week extension 
study (Study 204682), if baseline antibody levels or a reduction in titer are not achieved 
by the follow-up visit then additional samples for immunogenicity testing may be 
obtained every 30 days following the follow-up visit until baseline antibody levels, or 
reduced titres, are achieved. Subjects eligible for the extension study (Study 204682) will 
have immunogenicity samples taken as specified in protocol 204682.
The immunogenicity data in the case of severe allergic reactions will be listed.
8.2.4.
Adverse Events
All AEs will be coded using MedDRA which will be updated whenever available 
throughout the life of the study. Adverse events will be categorized by their occurrence in 
regard to therapeutic phase (pre-therapy, on-therapy, or post-therapy) as defined in 
Appendix 4. Adverse events will be summarized in various subsets by treatment group. 
An overview summary of the number and percentage of subjects with any AE, the total 
number of AEs recorded, and the overall AE density and incidence rate for on-therapy 
AEs will be provided by treatment group. The overview will also summarize SAEs, 
treatment-related AEs, AEs by maximum intensity, and AEs by therapy phase. 
Summaries of the number and percentage of subjects with any treatment-emergent AEs 
(TEAEs), related AEs, AEs leading to treatment discontinuation or withdrawal from 
study, SAEs, fatal AEs, will be provided. Adverse events will also be summarized by 
maximum intensity (mild, moderate, and severe).
AE summaries will not include hypoglycemic events, unless otherwise specified – The 
exceptions are summaries for serious AEs, AEs leading to withdrawal from 
treatment/study and pre-therapy AEs.
All AEs will be listed in a subject data listing.
8.2.4.1.
General Adverse Events Summaries
Summaries of the number and percentage of subjects with AEs and the total number of 
AEs will be provided by treatment group overall and at the SOC and PT level for the 
following time periods:
1) On-therapy and post-therapy combined period
2) Pre-therapy (includes hypoglycemia events)
3) On-therapy
4) Post-therapy 
In addition, on-therapy Adverse events will be presented by time intervals of onset (<=12 
weeks, >12 - <=26 weeks) and by treatment group; the on-therapy non-serious AEs will 
be summarized by treatment group.


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An additional on-therapy AE summary will also be provided following government 
clinical register format; these summaries will include the AEs of hypoglycemia event.
A by-subject listing of all AEs will also be presented.
8.2.4.2.
Treatment Emergent Adverse Events
TEAEs are defined as any AEs, regardless of relationship to the, randomized study drug 
(i.e., albiglutide or other study treatments), that occur after the first dose of the 
randomized study medication, which is equivalent to on-therapy and post-therapy AEs 
combined. Summaries of the number and percentage of subjects with TEAEs will be 
provided by treatment group overall at the SOC and PT level. TEAES will also be further 
defined as on-therapy or post-therapy AEs for summary purposes. 
A by-subject listing of all TEAEs will also be presented.
8.2.4.3.
Treatment-Related Adverse Events
Treatment-related AEs will be defined as any AEs that are considered by the investigator 
to have a reasonable possibility to be related to the study treatment. If a relationship to 
the study treatment is missing or unknown after the start of treatment it will be assumed, 
for the purpose of analyses, to be treatment-related. 
A summary of the number and percentage of subjects with treatment-related AEs will be 
displayed. The treatment-related AE data will be categorized and presented in a manner 
similar to that described above for the general AE summaries for both the on-therapy and 
post-therapy therapeutic phases.
8.2.4.4.
Adverse Events by Maximum Intensity
A summary of the number and percentage of subjects with on-therapy and post-therapy 
adverse events by intensity (mild, moderate, and severe) will be produced. The data will 
be sorted and categorized using the method and format described previously. 
Subjects who experience the same event several times with different intensity will only 
be counted once according to the maximum intensity experienced (for that therapeutic 
phase). 
8.2.4.5.
Most Common Adverse Events
A summary of most common on-therapy adverse events (>2% total incidence in any 
treatment arm) by treatment will be produced.
In addition, on-therapy non-serious AEs with proportion of subjects experiencing the AE 
>=5% among any of the active arms will be summarized by treatment group following 
government clinical register format; this summary will include AEs of hypoglycemia 
event.


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8.2.5.
Deaths and Serious Adverse Events
Serious adverse events (SAEs) will be summarized in a manner similar to that described 
above for the general AE summaries by treatment group for pre-therapy, on-therapy, and 
post-therapy therapeutic phases. Treatment-related SAEs will also be summarized 
separately by treatment group for both the on-therapy and post-therapy therapeutic 
phases.
SAE, fatal SAE and serious non-fatal AEs will also be summarized following 
government clinical register format; these summaries will include SAEs of hypoglycemia 
event.
Summaries and by subject listings of fatal AEs and serious non-fatal AEs will be 
presented. 
8.2.6.
Adverse Events Leading to Discontinuation of Investigational 
Product and/or Withdrawal from the Study
A summary of the number and percentage of subjects with adverse events leading to 
permanent discontinuation of study treatment from the study will be presented by 
treatment group for the on-therapy phase. 
A summary of the number and percentage of subjects with adverse events leading to 
withdrawal from the study will be presented for the on-therapy phase.
A by-subject listing of all adverse events leading to permanent discontinuation of study 
drug/withdrawal from the study will be produced.
8.2.7.
Adverse Events of Special Interest
For selected AEs of special interest such as hypoglycemia, the exposure-adjusted event 
rate, i.e., AE density, will be calculated as the number of events in a given period divided 
by the total person time on treatment of subjects at risk within the same period; the 
exposure-adjusted incidence rate will also be calculated as the number of subjects in a 
given period divided by the total person time on treatment of subjects at risk within the 
same period. The exposure-adjusted event rate and incidence rate will be expressed as an 
annualized rate (expected number of events or subjects per 100 person-years).
For any AEs of special interest, summary tables and by subject data listings will be 
provided. 
8.2.7.1.
Hypoglycemic Events
Hypoglycemic events merit special attention in the development and study of drugs for 
the treatment of T2DM since they are often related to the efficacy of a compound. In 
order to accomplish this, hypoglycemic event data including supplemental hypoglycemic 
event information not collected on AE eCRF page are reported on a separate 
hypoglycemic event eCRF page. However, any hypoglycemic event that meets the 
criteria for a serious AE will also be included in the serious AE summaries.


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Analysis of on-therapy hypoglycemic events will include all AEs coded to the preferred 
term of ‘Hypoglycemia’. For on-therapy hypoglycemic events the number and percentage 
of subjects with events, the number of events, the incidence rate (per 100 person-years) 
and AE density (per 100 person-years) by the severity of the event defined by American 
Diabetes Association [ADA], SAE status, relationship to the investigational product, and 
withdrawal status will be summarized by treatment group. The events will also be 
summarized according to intervention provided, action taken with regard to background 
and anti-hyperglycemic medications and onset week and glucose levels. All 
hypoglycemic events will be classified as severe, documented symptomatic, 
asymptomatic, probable symptomatic, or pseudohypoglycemia per the American 
Diabetes Association criteria. 
The incidence of hypoglycemia with blood glucose <56 mg/dL (<3.1 mmol/L), regardless 
of symptoms, will also be summarized by treatment group. 
On-therapy hypoglycemic events over time will be summarized by onset week and 
plotted for each treatment group.
A by-subject listing of all hypoglycemic events will be produced.
8.2.7.2.
Cardiovascular Events
A summary of the number and percentage of subjects with cardiovascular events will be 
reported by treatment group and therapeutic phase.
A by-subject listing of all the data elements collected on the eCRF page will be presented 
for subjects who experience cardiovascular events.
8.2.7.3.
Pancreatitis and Pancreatic Cancer
The number and percent of subjects with pancreatitis and pancreatic cancer will be 
reported by treatment group. A by-subject listing of all the data elements collected on 
pancreatitis event page of the eCRF will be presented for subjects who experienced 
pancreatitis and pancreatic cancer. This listing of the pancreatitis events will also include 
the adjudication results as determined by the independent pancreatitis adjudication 
committee. 
8.2.7.4.
Thyroid Adverse Events
The number and percent of subjects with thyroid AEs will be reported by treatment 
group. Additionally thyroid adverse events identified by a customized MedDRA query 
will be presented by treatment group.
A by-subject listing of all the data elements captured in the thyroid tumor eCRF page will 
be produced.
8.2.7.5.
Gastrointestinal (GI) Events
A summary of the number and percentage of subjects with GI events (specifically, AEs 
coded to the MedDRA SOC of gastrointestinal disorders) will be reported by treatment 


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group and therapeutic phase (pre-, on-, or post-therapy). Also, summaries of on-therapy 
GI events that lead to withdrawal of active treatment, treatment-related and serious GI 
events (including those that do not necessarily lead to withdrawal of active treatment) 
will be presented separately by treatment group.
For each subject, the time to first occurrence of a GI event is calculated as the number of 
days between the randomization date and the date of onset of the first on-therapy GI 
event plus 1. Subjects who do not experience any GI events will be censored at the last 
dose date + 25 days. The median time to first occurrence of a GI event as well as the 
Kaplan-Meier probability of first occurrence of a GI event at various time points will be 
presented for each treatment group. 
The prevalence of GI events will be reported and plotted by treatment group. 
The number and percentage of subjects reporting nausea at each study week will be 
presented by treatment group. Each week will include those subjects with onset of nausea 
during that particular week and also those subjects with nausea that started during a 
previous week but has not resolved. The prevalence of nausea will also be plotted over 
time. Similar summaries and plots will be presented for subjects reporting events of 
diarrhea and also separately for subjects reporting events of vomiting. In addition, a 
combined summary and accompanying plot of the number and percentage of subjects 
reporting events of nausea and/or vomiting will be presented.
8.2.7.6.
Systemic Allergic Reactions
Systemic allergic reactions are reported by the investigators on the eCRF. The number 
and percentage of subjects with suspected systemic allergic reactions will be presented by 
treatment group. In addition, the time to first occurrence of a systemic allergic reaction 
will be analyzed and presented in a manner identical to that described above for first 
occurrence of a GI event.
A summary of systemic allergic reactions based on Customized MedDRA Query (CMQ) 
list identified by GSK will also be presented. Analyses will be repeated for this data.
8.2.7.7.
Liver Events
The number and percentage of subjects with liver events that have been identified by 
investigators on the liver events eCRF page will be presented by treatment group. 
Additionally, liver events identified by a customized MedDRA query will also be 
presented by treatment group. By-subject listings of all the data elements collected on the 
eCRF page will be presented for subjects who experience adverse liver events, as 
identified by the investigators.
8.2.7.8.
Atrial Fibrillation/Flutter
The number and percentage of subjects with Atrial Fibrillation/Flutter events will be 
presented by treatment group for Atrial Fibrillation and Atrial Flutter. By-subject listings 
of all the data elements collected on the Atrial Fibrillation and Atrial Flutter event eCRF 


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page will be presented for subjects who experience atrial fibrillation/flutter events, as 
reported by the investigators.
8.2.7.9.
Pneumonia
The number and percentage of subjects with Pneumonia events will be presented by 
treatment group for Pneumonia event reported by the investigator on the eCRF. Summary 
of Pneumonia events identified by a customized MedDRA query will also be provided. 
By-subject listings of all the data elements collected on the Pneumonia event eCRF page 
will be presented for subjects who experience pneumonia events, as reported by the 
investigators.
8.2.7.10.
Diabetic Retinopathy
The number and percentage of subjects with diabetic retinopathy events will be presented 
by treatment group. A by-subject listing of all the data elements collected on the diabetic 
retinopathy eCRF page will be presented for subjects who experience diabetic 
retinopathy, as reported by the investigators.
8.2.7.11.
Appendicitis
The preferred terms containing the word “appendicitis” will be identified as Appendicitis 
events. The number and percentage of subjects with appendicitis will be presented by 
treatment group and a by-subject listing will be presented. 
8.2.7.12.
Malignant Neoplasm
Malignant neoplasm will be captured in the AE eCRF pages. The number and 
percentages of subjects with malignant neoplasm identified by a customized MedDRA 
query will be presented by treatment group and a by-subject listing will be presented.
8.2.8.
Pregnancies
A listing of subject pregnancies will be provided. 
8.2.9.
Clinical Laboratory Evaluations
Laboratory results that are beyond the limits of quantification will have the inequality 
sign dropped (<, ≤, >, or ≥) and the quantification limit will be used as the numeric result 
for summarization.  
8.2.9.1.
Chemistry, Hematology and Urinalysis
Laboratory parameters include the following tests: hematology, chemistry and urinalysis. 
Established or generally acknowledged methods, normal ranges, and quality control 
procedures will be supplied by central lab for the study records. 
Hematology parameters used in summaries include complete blood count with red blood 
cell indices, white blood cell count with differential, and platelet count. Chemistry 
parameters (including lipids) used in summaries include blood urea nitrogen (BUN), 


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potassium, aspartate aminotransferase (AST), total and direct bilirubin, creatinine, 
sodium, ALT, total protein, calcium, chloride, alkaline phosphatase (ALP), albumin, 
bicarbonate, uric acid, gamma glutamyl transferase (GGT), estimated glomerular 
filtration rate (eGFR), and lipids (including total cholesterol, LDL-C, HDL C, 
triglycerides, free fatty acids). Urinalysis include specific gravity, pH, glucose, protein, 
blood and ketones by dipstick and microscopic examination (if blood or protein is 
abnormal). Note that white blood cell absolute count was not collected in the study.
All laboratory parameters will be summarized, for each treatment group, at every 
scheduled assessment time point using descriptive statistics and presented graphically. In 
addition, for hematology and chemistry laboratory parameters, change from Baseline in 
these quantitative tests will be summarized by treatment group and at every scheduled 
assessment postbaseline time point. Shift tables providing the number and percentage of 
subjects with indicated shifts (normal, abnormal not of clinical concern, abnormal of 
clinical concern) in their results from baseline to each scheduled postbaseline assessment 
will also be presented for all hematology and chemistry parameters. 
Additionally, the number of subjects with laboratory values of potential clinical concern 
will be summarized by treatment group and scheduled assessment time point for 
hematology and chemistry. The criteria for laboratory values of potential clinical concern 
are detailed in Appendix 7: Values of Potential Clinical Importance. 
A summary of laboratory values of potential clinical concern will be provided for liver 
function tests, including ALT, AST, and total bilirubin. The criteria for liver function 
tests of potential clinical concern are detailed in Appendix 7: Values of Potential Clinical 
Importance.
All summaries will be done for the safety population and all laboratory data will be listed 
including other laboratory tests, such as HIV, Lipase, Amylase, hepatitis B, hepatitis C, 
TSH, and urine pregnancy test results. 
8.2.10.
Other Safety Measures
8.2.10.1.
Vital Signs
The vital sign summary and analysis will include systolic blood pressure (mmHg), 
diastolic blood pressure (mmHg), and heart rate (bpm).
Each vital sign parameter at every scheduled assessment time point will be summarized 
using descriptive statistics and presented graphically. Change from Baseline will also be 
summarized using descriptive statistics and presented graphically. Additionally, the 
number of subjects with vital signs of potential clinical concern will also be summarized. 
Shift tables providing the number and percentage of subjects with indicated shifts 
(normal, low value of clinical concern, high value of clinical concern) in their results 
from baseline to each scheduled postbaseline assessment will also be presented. The 
criteria for vital signs of potential clinical concern are detailed in Appendix 7: Values of 
Potential Clinical Importance. 
All summaries will be done for the safety population and all vital sign data will be listed. 


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8.2.10.2.
Electrocardiograms
ECG parameters collected at each scheduled assessment time point include heart rate, 
QRS interval, QT interval, QT interval – Bazett correction (QTcB), QT interval –
Fridericia correction (QTcF), RR interval and PR interval. 
Each ECG parameter at each scheduled assessment time point will be summarized by 
treatment group using descriptive statistics and presented graphically. Change from 
Baseline will also be summarized using descriptive statistics. A summary of the number 
and percentage of subjects in overall ECG interpretation and abnormal findings will be 
displayed by treatment group. The number of subjects with ECG values of potential 
clinical concern will also be summarized. Shift tables providing the number and 
percentage of subjects with indicated shifts (normal, low value of clinical concern, high 
value of clinical concern) in their results from baseline to each scheduled postbaseline 
assessment will also be presented. The criteria for ECG values of potential clinical 
concern are detailed in Appendix 7: Values of Potential Clinical Importance. 
Additional notable abnormality criteria are defined based on the corrected QT interval 
(both QTcB and QTcF values) as the following: >450 msec, >480 msec, >500 msec, >30
msc increase from baseline, and >60 msec increase from baseline. The numbers and 
percentages of subjects who have notable abnormalities at any time post-baseline will be 
presented overall and by treatment group.
All summaries will be done for the safety population and all ECG data will be listed. 
8.2.10.3.
Physical Exams
In this study, findings from physical exams will be recorded in the AE eCRF page or 
medical history CRF page by the investigator as deemed appropriate. No separate 
summary of physical exams will be provided.


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8.3.
Pharmacokinetic Analyses
Blood samples for the determination of albiglutide plasma concentrations will be 
obtained from all subjects before administration of study treatment at Week 12 and Week 
26/early withdrawal. During visits where ECGs and vital sign measurements
are required, blood samples will be collected after measurement of ECGs and vital signs.
Albiglutide concentrations will be summarized by treatment group at each visit using 
descriptive statistics (n, mean, SD, coefficient of variation [%], median, minimum, 
maximum, geometric mean and geometric mean coefficient of variation [%]). 
Data will be summarized for the PK population and individual subject concentration data 
will be listed.
8.3.1.
Overview of Planned Analyses
The PK analyses will be based on the PK population.
Table 6 provides an overview of the planned analyses, with further details of data 
displays being presented in Appendix 14: List of Data Displays.
Table 6
Overview of Planned PK Analyses
Endpoints
Observed
Change from Baseline
Summary
Individual
Summary
Individual
T
F
F
L
T
F
F
L
Summary of [Analyte] [Matrix] 
Pharmacokinetic Concentration-Time Data by 
treatment group
Y
Y
Y
Summary of [Analyte] Pharmacokinetic Urine 
Excretion Rate-Time Data by treatment group
Y
Y
Y
NOTES :

T = Table, F = Figure, L = Listing, Y = Yes display generated.

Stats Analysis = Represents TFL related to any formal statistical analyses (i.e. modelling) conducted.

Summary = Represents TFL related to any summaries (i.e. descriptive statistics) of the observed raw data.

Individual = Represents FL related to any displays of individual subject observed raw data.
8.4.
Pharmacogenetic data analyses
Additional blood samples drawn for pharmacogenetic (PGx) analysis will be stored and 
may be analyzed in the future for exploratory study of variability in drug response 
because of hereditary factors in different populations. Whenever applicable, the details of 
these analyses will be described in a separate document. See the protocol for details about 
the Pharmacogenetics Analysis Plan.


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9.
OTHER STATISTICAL ANALYSES
Not applicable.


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10.
REFERENCES
American Diabetes Association. Standards of Medical Care in Diabetes—2010. Diabetes 
Care. 2010;33;S11-S61. 
Carpenter J.R., Kenward M.G. 2013. Multiple Imputation and its Application. 
Chichester: John Wiley & Sons.
Food and Drug Administration (FDA). Guidance for Industry. Non-Inferiority Clinical 
Trials. U.S. Department of Health and Human Services. Food and Drug Administration. 
Center for Drug Evaluation and Research (CDER). Center for Biologics Evaluation and 
Research (CBER). March 2010 Clinical/Medical. Available from: 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM202140.pdf.
GSK Document No. : 2014N210004_02. A Repeat-dose Study in Subjects with Type 2 
Diabetes Mellitus to Assess the Efficacy, Safety, Tolerability and Pharmacodynamics, of 
Albiglutide Liquid Drug Product. 26 May 2016
Hintze, J. PASS 12. NCSS, LLC. Kaysville, Utah, USA. 2013. Available at 
http://www.ncss.com.
Koch, G. Comments on ‘Current issues in non-inferiority trials’. Statistics in Medicine. 
2008; 27: 333-342
Rubin D.B. 1987. Multiple Imputation for Nonresponse in Surveys. New York: John 
Wiley & Sons.
Siddiqui O, Hung HM, O’Neill R. MMRM vs. LOCF: a comprehensive comparison 
based on simulation study and 25 NDA datasets. J Biopharm Stat. 2009;19 (2):227-46.


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11.
APPENDICES
Section
Appendix
RAP Section 4 : Analysis Populations
Section 11.1
Appendix 1: Protocol Deviation Management and Definitions for Per Protocol 
Population
RAP Section 5 : General Considerations for Data Analyses & Data Handling Conventions
Section 11.2
Appendix 2: Time and Events
Section 11.3
Appendix 3: Assessment Windows
Section 11.4
Appendix 4: Treatment Periods
Section 11.5
Appendix 5: Derived and Transformed Data
Section 11.6
Appendix 6: Premature Withdrawals & Handling of Missing Data
Section 11.7
Appendix 7: Values of Potential Clinical Importance
Section 11.8
Appendix 8: Multicentre Studies
Section 11.9
Appendix 9: Examination of Covariates, Subgroups & Other Strata
Section 11.10
Appendix 10: Multiple Comparisons and Multiplicity
Section 11.11
Appendix 11: Model Checking and Diagnostics for Statistical Analyses
Other RAP Appendices
Section 11.12
Appendix 12: Sample Size Considerations
Section 11.13
Appendix 13: Abbreviations & Trade Marks
Section 11.14
Appendix 14Appendix 14: List of Data Displays


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11.1.
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population
11.1.1.
Exclusions from Per Protocol Population 
Final list of protocol deviations that lead to exclusion from Per-Protocol population will 
be determined by the study team and populated here toward the end of the study. 
A subject meeting any of the following criteria may be excluded from the Per Protocol 
population based on clinical judgement in a case-by-case basis. In addition, other 
deviations that may not fall under the following criteria may be excluded from the per 
protocol population based on a case by case basis:
Number
Protocol Deviation Description
01
Concomitant Medication

Subject took medication prohibited by protocol (SAFETY)

Subject took medication prohibited by protocol (EFFICACY)
02
Study Treatment Compliance

Subject did not receive >= 80% of planned medication
03
Inclusion Criteria and Exclusion Criteria

Subject enrolled but did not meet all protocol inclusion criteria at screening.

Subject enrolled but met exclusion criteria at screening.
04
Study Treatment Admin/Dispense

Incorrect study medication kit and/or pen dispensed to subject.
05
ICF (Informed Consent Form) Process/Timing

ICF(s) not obtained prior to any study procedure.

Site staff did not sign and/or date ICF.

Genetic blood sample collected without subject consent.

ICF re-consenting issues/delays

Incorrect ICF used
06
Missing Endpoint Assessments

HbA1c blood sample not collected or insufficient/deficient at baseline or Week 26
11.1.2.
Significant Protocol Deviation Rules
The Significant Protocol Deviation Rules Version 1.1, dated 21JUN2017, will be used to 
identify the significant protocol deviations. It is intended to categorize significant 
protocol deviations that are anticipated to occur in a study and to document study-specific 
requirements for cross-functional team review of these significant protocol deviations and 
other deviations that may occur in the study. 
Part A of the Significant Protocol Deviation Plan is a list of the frequency that all 
deviations (protocol and GCP) will undergo review by a cross-functional team. (Review 


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should assess trending and appropriate categorization (both deviation type and 
significance)).
Part B is a list of each significant protocol deviation in the appropriate category and 
indicates the criterion that makes the deviation significant. Non-significant deviations 
should not be included.
This Significant PD Rules document should be updated when changes are identified (e.g., 
new deviation, re-classification of significance of a deviation). The revised document 
should describe changes in the Change History and appropriate version control should be 
applied.  


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11.2.
Appendix 2: Time & Events
11.2.1.
Protocol Defined Time & Events
Procedure
Treatment
Visit
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Week15
-2
0
1
2
3
4
5
6
7
8
9
10
11
12
Visit Window
-14d
0d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
Informed consent
X
Demography/medical history
X
HIV, hepatitis B and C, amylase, lipase, 
alcohol and drug  screen, TSH
X
Inclusion/exclusion criteria review
X
X1
Full (F) or brief (B) physical exam2
F
B
B
B
Height (H),Weigh (W), BMI 
H, W, 
BMI
W
W
12-lead ECG3
X
X
X
X
X
Vital signs3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum (S)/Urine (U) pregnancy test 
(WCBP)
S
U
U
U
U
Clinical chemistry/hematology samples4
X
X
X
X
Lipids (including total cholesterol, LDL-
C, HDL C, triglycerides, FFAs)4
X
Urinalysis
X
HbA1c 5, 8
X
X
X
X
X
X
eGFR
X
X
X
Immunogenicity sample6
X
X
X
X
X
Genetic sample7
X
FPG 8
X
X
X
X
X
X
X
X
X
X
X
X
X
PK samples9
X
Review AE/SAE, concomitant 
medication and hypoglycemia events 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Advice on diet and exercise10
X
X
X
X
X
X
X
X
X
X
X
X
X
Register visit into IVRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X


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Randomization11
X
Study Treatment 
X
X
X
X
X
X
X
X
X
X
X
X
X
Procedure
Treatment
End of 
Treatment
12, 13
Follow-
up14
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week15
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
Visit Window
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±7d
Informed consent
Demography/medical history
HIV, hepatitis B and C, amylase, lipase, 
alcohol and drug  screen, TSH
Inclusion/exclusion criteria review
Full (F) or brief (B) physical exam2
B
B
B
B
F
F
Height (H),Weigh (W), BMI 
W
W
W
W
W
W
12-lead ECG3
X
Vital signs
X
X
X
X
X
X
X
X
Serum (S)/Urine (U) pregnancy test (WCBP)
U
U
U
U
S
U
Clinical chemistry/hematology samples4
X
X
Lipids (including total cholesterol, LDL-C, 
HDL C, triglycerides, FFAs)4
X
X
Urinalysis
X
HbA1c 5, 8
X
X
X
X
eGFR
X
X
X
Immunogenicity sample6
X
X
X
X
X
Genetic sample7
FPG 8
X
X
X
X
X
PK samples9
X
Review AE/SAE, concomitant medication 
and hypoglycemia events 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Advice on diet and exercise10
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Register visit into IVRS
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization11


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Procedure
Treatment
End of 
Treatment
12, 13
Follow-
up14
Visit
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
Week15
13
14
15
16
17
18
19
20
21
22
23
24
25
26
34
Visit Window
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±3d
±7d
Study Treatment 
X
X
X
X
X
X
X
X
X
X
X
X
X
TSH: thyroid stimulating hormone; BMI: body mass index; WCBP: women of child bearing potential; FFA: free fatty acids; LDL-c:  low density lipoproteins cholesterol; 
HDL-c: high density lipoproteins cholesterol; d, day
1.
Before dosing, the investigator must review all inclusion and exclusion criteria to confirm subject’s eligibility. If a subject no longer meets all of the eligibility criteria (e.g., there is 
evidence of a new myocardial infarction (MI) on an ECG or ALT, etc. are out of range), do not administer the study treatment and contact the medical monitor to discuss how to
proceed (e.g., to determine if repeat testing is warranted). 
2.
Details of full and brief physical examinations are provided in Protocol Section 7.4.3.
3.
12-lead ECGs will be obtained before measurement of vital signs and collection of blood samples for laboratory testing. Vital signs measurement will be taken before collection of 
blood samples. See Protocol Section 7.4.5.
4.
Clinical chemistry and hematology assessments are described in Protocol Section 7.4.6.
5.
Blood samples for HbA1c should be collected before administration of study treatment.
6.
Blood samples for immunogenicity are to be collected before study drug administration at the times specified in Protocol Section 7.1.  A follow-up sample will be taken from each 
subject 8 weeks after the final dose of albiglutide is administered.
7.
Blood sample for genetics can be collected at any time during the study after the genetics informed consent has been obtained and the subject has been randomly assigned to 
treatment group. 
8.
Subjects will have their FPG and HbA1c levels evaluated to monitor for potential hyperglycemia.
9.
PK samples (trough) will be obtained prior to dosing (Protocol Section 7.6).
10. Standard diabetic dietary and exercise advice will be provided at Visit 2 and reinforced through the end-of-treatment visit.
11. Once the HbA1c results have been received from the central laboratory and all other eligibility criteria are met, study centre personnel will call the IVRS to obtain the subject’s 
treatment assignment.
12. Subjects who discontinue study treatment should be handled as described in Protocol Section 5.5.
13. The end of treatment visit in Study 200952.is also Visit 1 of 204682 for those subjects continuing into the extension study.
14. Follow-up visit for subjects who have stopped investigational product (see Protocol Section 5.5), withdrawn from the study or who have completed the 26 week treatment period, 
but do not consent and/or are not eligible to participate in the 26 week extension study (Study 204682).
15. All visits will have a treatment window as in the table. Baseline (Week 0) serves as the reference point. Subjects will not be considered out of compliance if visit windows extend 
because of extraordinary events that make it impossible for subjects to complete a visit within the above window (e.g., holidays, vacations, personal emergencies). Determination 
of the maximum visit window deviation is at the discretion of the medical monitor


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11.2.2.
Schedule of Assessments for Subjects Who Permanently Discontinue Investigational Product
Procedure
Continue Scheduled Clinic 
Visit
(Weeks 4, 8, 12,16,20) 4,5
Week 26
(Equivalent to End of 
Treatment Visit)
Follow-up
Week 34
Full (F) or brief (B) physical exam
B
F
F
Weight
X
X
X
12-lead ECG 1
X
X
Vital Signs
X
X
X
Clinical chemistry/hematology samples2
X
X
X
HbA1c and FPG 3
X
X
X
Review AE/SAE, concomitant medication and 
hypoglycaemia events
X
X
X
1.
12-lead ECGs will be obtained before measurement of vital signs and collection of blood samples for laboratory testing. Vital signs measurement will be taken before collection of 
blood sample. See Protocol Section 7.4.5.
2.
Clinical chemistry and hematology assessments are described in Protocol Section 7.4.6.
3.
Subjects will have their FPG and HbA1c levels evaluated to monitor for potential hyperglycemia.
4.
Week will be dependent on when the subject discontinues investigational product. Subjects will start this schedule as soon as possible following investigational product
discontinuation and timings of visits will be the same as for if the subject was continuing on investigational product. The timing of the clinic visits can be modified at the discretion
of the investigator. All subjects must attend the Week 26 visit.
5.
Additional unscheduled visits will occur as medically necessary.


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11.3.
Appendix 3: Assessment Windows
11.3.1.
Definitions of Baseline and Study Day
In general, the baseline value for each variable will be defined as the last measurement 
collected prior to the first dose of randomized study medication.
Study day will be defined as the number of days from the first dose of randomized study 
medication. The date when a subject receives the first dose of randomized study 
medication is defined as Day 1. For events after the first dose date, study day is 
calculated as the difference in days between the first dose date and the date of interest, 
plus 1 day. For events that occur before the first dose date, study day is calculated as the 
difference in days between the first dose date and the date of interest. Thus, the day 
before first dose date is defined as Day -1.
Note that the date of first dose is Day 1 and the day before the date of first dose is Day -1 
(there is no Day 0).
11.3.2.
Visit Slotting Algorithm
For all safety and efficacy parameters to be summarized or analyzed by visit, data records 
will be slotted to one of the protocol specified visits using the following algorithm: 
a) Determine the therapy period and study day for all records using the algorithms from 
Appendix 4: Treatment Periods.
b) For all records (including unscheduled visit records , early withdrawal records and 
repeat visit records), use the therapy period and study day determined above with the 
slotting intervals in the respective Table Analysis Visit Windows below to slot the 
record to the appropriate analysis visit.
Safety assessments:

For records determined to be in the pre-therapy period, the Screening (Week -
2) and Baseline (Week 0) analysis visits will be based on the nominal visits 
recorded on the eCRF. 

For records determined to be in the on-therapy period, use the study day with 
the slotting intervals in the respective table below to assign the records to the 
appropriate on-therapy analysis visit (Week 1 through Week 26).

For records determined to be in the post-therapy period, the study day will not 
be used for assigning the analysis visit. Instead, all post-therapy period 
records for subjects who complete randomized study treatment according to 
protocol will be assigned to the Week 34 post-therapy analysis visit. For 
subjects who terminate study treatment early, all post-therapy period records 
will be assigned to the 8 Week Follow up Visit. 


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Efficacy assessments (HbA1c and FPG):

For records determined to be in the pre-therapy period, the Screening (Week -
2) and Baseline (Week 0) analysis visits  will be based on the nominal visits 
recorded on the eCRF. 

For records determined to be in the on-therapy or post-therapy period, use the 
study day with the slotting intervals in the respective table below to assign the 
records to the appropriate on-therapy analysis visit (Week 1 through Week 
34).
11.3.3.
Multiple Evaluations
After all the records have been slotted based on therapy period and study day, if there are 
multiple valid records for an assessment within an assigned analysis visit, only one of 
these records will be used for summary statistics and analyses. The record to be used is 
determined using the following hierarchy (in decreasing order of priority):

the record closest to the target visit day

the record with an original nominal visit that matches the analysis visit

the record earliest in time for post-baseline assessments; for baseline, it is the 
record latest in time
11.3.4.
Analysis Visit Windows
For vital sign assessments (except weight):
Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Pre-therapy
Screening (Week -2)
-14
Not applicable
Baseline (Week 0)
1
Not applicable
On-therapy
Week 1
8
2 to 11 days
Week 2
15
12 to 18 days
Week 3
22
19 to 25 days
Week 4
29
26 to 32 days
Week 5
36
33 to 39 days
Week 6
43
40 to 46 days
Week 7
50
47 to 53 days
Week 8
57
54 to 60 days
Week 9
64
61 to 67 days
Week 10
71
68 to 74 days
Week 11
78
75 to 81 days
Week 12
85
82 to 92 days
Week 14
99
93 to 106 days
Week 16
113
107 to 120 days
Week 18
127
121 to 134 days


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Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Week 20
141
135 to 148 days
Week 22
155
149 to 165 days
Week 25
176
166 to 179 days
Week 26 (End of Treatment 
Visit)*
183
180 to (last dose date + 25 
days)
Post-therapy
Week 34**
239
>Last dose date + 25 days
8 Week Follow-up Visit**
Last dose date + 63 days***
>Last dose date + 25 days
* Week 26 is the end of treatment visit for those subjects completing the study per-protocol. For subjects who withdraw 
early from study treatment, the end of treatment visit will be assigned to an analysis visit based on the visit slotting 
algorithm using study day and therapy phase.
** Week 34 is the 8 week post-treatment follow-up visit for those subjects completing the study per-protocol. The 8 Week 
Follow-up Visit is the 8 week post-treatment follow-up visit for those subjects who withdraw early from study treatment. 
Both visits will be assigned based on the visit slotting algorithm using therapy phase.
*** The target study day for the 8 Week Follow-up Visit for subjects who withdraw early from study treatment is set to be 9
weeks (63 days) after last dose to correspond with the timing of the 8 week post-treatment follow-up for subjects 
completing the study per-protocol (where last dose is at Week 25 and the follow-up visit is at Week 34). 
For ECG assessments:
Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Pre-therapy
Week -2
-14
Not applicable
Baseline (Week 0)
1
Not applicable
On-therapy
Week 2
15
2 to 22 days
Week 4
29
23 to 43 days
Week 8
57
44 to 120 days
Week 26 (End of Treatment 
Visit)*
183
121 to (last dose date + 25 
days)
Post-therapy
Week 34**
239
>Last dose date + 25 days
8 Week Follow-up Visit**
Last dose date + 63 days***
>Last dose date + 25 days
* Week 26 is the end of treatment visit for those subjects completing the study per-protocol. For subjects who withdraw 
early from study treatment, the end of treatment visit will be assigned to an analysis visit based on the visit slotting 
algorithm using study day and therapy phase.
** Week 34 is the 8 week post-treatment follow-up visit for those subjects completing the study per-protocol. The 8 Week 
Follow-up Visit is the 8 week post-treatment follow-up visit for those subjects who withdraw early from study treatment. 
Both visits will be assigned based on the visit slotting algorithm using therapy phase.
*** The target study day for the 8 Week Follow-up Visit for subjects who withdraw early from study treatment is set to be 9 
weeks (63 days) after last dose to correspond with the timing of the 8 week post-treatment follow-up for subjects 
completing the study per-protocol (where last dose is at Week 25 and the follow-up visit is at Week 34). 
For lab assessments:
Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Pre-therapy
Week -2
-14
Not applicable
On-therapy
Week 1
8
2  to 18 days
Week 4
29
19 to 43 days
Week 8
57
44 to 85 days
Week 16
113
86 to 148 days


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Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Week 26 (End of Treatment 
Visit)*
183
149 to (last dose date + 25 
days)
Post-therapy
Week 34**
239
>Last dose date + 25 days
8 Week Follow-up Visit**
Last dose date + 63 days***
>Last dose date + 25 days
* Week 26 is the end of treatment visit for those subjects completing the study per-protocol. For subjects who withdraw 
early from study treatment, the end of treatment visit will be assigned to an analysis visit based on the visit slotting 
algorithm using study day and therapy phase.
** Week 34 is the 8 week post-treatment follow-up visit for those subjects completing the study per-protocol. The 8 Week 
Follow-up Visit is the 8 week post-treatment follow-up visit for those subjects who withdraw early from study treatment. 
Both visits will be assigned based on the visit slotting algorithm using therapy phase.
*** The target study day for the 8 Week Follow-up Visit for subjects who withdraw early from study treatment is set to be 9 
weeks (63 days) after last dose to correspond with the timing of the 8 week post-treatment follow-up for subjects 
completing the study per-protocol (where last dose is at Week 25 and the follow-up visit is at Week 34). 
For immunogenicity assessments:
Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Pre-therapy
Baseline (Week 0)
1
Not applicable
On-therapy
Week 2
15
2 to 22 days
Week 4
29
23 to 43 days
Week 8
57
44 to  71 days
Week 12
85
72 to 99 days
Week 16
113
100 to 127 days
Week 20
141
128 to 155 days
Week 24
169
156 to 176 days
Week 26 (End of Treatment 
Visit)*
183
177 to (last dose date + 25 
days)
Post-therapy
Week 34**
239
>Last dose date + 25 days
8 Week Follow-up Visit**
Last dose date + 63 days***
>Last dose date + 25 days
* Week 26 is the end of treatment visit for those subjects completing the study per-protocol. For subjects who withdraw 
early from study treatment, the end of treatment visit will be assigned to an analysis visit based on the visit slotting 
algorithm using study day and therapy phase.
** Week 34 is the 8 week post-treatment follow-up visit for those subjects completing the study per-protocol. The 8 Week 
Follow-up Visit is the 8 week post-treatment follow-up visit for those subjects who withdraw early from study treatment. 
Both visits will be assigned based on the visit slotting algorithm using therapy phase.
*** The target study day for the 8 Week Follow-up Visit for subjects who withdraw early from study treatment is set to be 9 
weeks (63 days) after last dose to correspond with the timing of the 8 week post-treatment follow-up for subjects 
completing the study per-protocol (where last dose is at Week 25 and the follow-up visit is at Week 34). 
For weight assessments:
Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Pre-therapy
Week -2
-14
Not applicable
On-therapy


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Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Week 4
29
2 to 43 days
Week 8
57
44 to 74 days
Week 13
92
75 to 102 days
Week 16
113
103 to 127 days
Week 20
141
128 to 158 days
Week 25
176
159 to 179 days
Week 26 (End of Treatment 
Visit)*
183
180 to (last dose date + 25 
days)
Post-therapy
Week 34**
239
>Last dose date + 25 days
8 Week Follow-up Visit**
Last dose date + 63 days***
>Last dose date + 25 days
* Week 26 is the end of treatment visit for those subjects completing the study per-protocol. For subjects who withdraw 
early from study treatment, the end of treatment visit will be assigned to an analysis visit based on the visit slotting 
algorithm using study day and therapy phase.
** Week 34 is the 8 week post-treatment follow-up visit for those subjects completing the study per-protocol. The 8 Week 
Follow-up Visit is the 8 week post-treatment follow-up visit for those subjects who withdraw early from study treatment. 
Both visits will be assigned based on the visit slotting algorithm using therapy phase.
*** The target study day for the 8 Week Follow-up Visit for subjects who withdraw early from study treatment is set to be 9 
weeks (63 days) after last dose to correspond with the timing of the 8 week post-treatment follow-up for subjects 
completing the study per-protocol (where last dose is at Week 25 and the follow-up visit is at Week 34). 
For HbA1C assessments:
Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Pre-therapy
Week -2
-14
Not applicable
Baseline (Week 0)
1
Not applicable
On-therapy or post-therapy*
Week 1
8
2  to 18 days
Week 4
29
19 to 43 days
Week 8
57
44 to 71 days
Week 12
85
72 to 99 days
Week 16
113
100 to 127 days
Week 20
141
128 to 162 days
Week 26 (End of Treatment Visit)
183
163 to 211 days
Week 34
239
>211 days
* For all subjects regardless their study drug discontinuation status, their on-therapy or post-therapy 
period assessments will be slotted in the same way to the appropriate analysis visits per the above 
defined slotting intervals.
For FPG assessments:
Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Pre-therapy
Baseline (Week 0)
1
Not applicable
On-therapy or post-therapy*
Week 1
8
2  to 11 days
Week 2
15
12 to 18 days
Week 3
22
19 to 25 days
Week 4
29
26 to 32 days
Week 5
36
33 tp 39 days


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Scheduled Visit
Target Study Day of Visit
Slotting Intervals
Week 6
43
40 to 46 days
Week 7
50
47 to 53 days
Week 8
57
54 to 60 days
Week 9
64
61 to 67 days
Week 10
71
68 to 74 days
Week 11
78
75 to 81 days
Week 12
85
82 to 88 days
Week 13
92
89 to 102 days
Week 16
113
103 to 127 days
Week 20
141
128 to 162 days
Week 26 (End of Treatment Visit)
183
163 to 211 days
Week 34
239
>211 days
* For all subjects regardless their study drug discontinuation status, their on-therapy or post-therapy 
period assessments will be slotted in the same way to the appropriate analysis visits per the above 
defined slotting intervals.


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11.4.
Appendix 4: Treatment Periods
For classifying AEs (including hypoglycemic events), the therapy periods will be defined 
as: 

Pre-therapy: The onset date of the AE is before the start date of randomized 
study medication. If the onset date of the AE is on the start date of randomized 
study medication, the AE will be considered as on-therapy.

On-therapy: The onset date of the AE is on or after the start date of randomized 
study medication and within 25 days after the date of last dose.

Post-therapy: The onset date of the AE is more than 25 days after the last date of 
randomized study medication.
For immunogenicity data and other safety parameters that are assessed prior to 
administration of randomized study medication on dosing days, the therapy periods will 
be defined as:   

Pre-therapy: The assessment date is on or before the start date of randomized 
study medication. 

On-therapy: The assessment date is after the start date of randomized study 
medication and within 25 days after the date of last dose.

Post-therapy: The assessment date is more than 25 days after the last date of 
randomized study medication.
For an AE with an incomplete start date where the year and month are present while the 
day is missing, or where the year is present while both month and day are missing, the 
date is imputed in a dynamic way consistent with the partial date information so that the 
resulting AE therapy period assignment based on the imputed date is the most 
conservative possible, where the order from the most to the least conservative is: on-
therapy phase > post-therapy phase > pre-therapy. Note that if the AE stop date is 
present, then the imputed start date will always be on or prior to the stop date.


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11.5.
Appendix 5: Derived and Transformed Data
11.5.1.
Change from Baseline
The baseline value for an assessment is defined as the last available nonmissing value 
prior to the first dose of the randomized treatment. Change from Baseline is defined as 
the postbaseline value minus the baseline value for the given assessment.
11.5.2.
Body Mass Index Calculation
Body mass index (BMI) will be calculated as follows:
BMI = weight (kg)
[height (m)]2
11.5.3.
Total Person Time on Treatment
The total person time on albiglutide treatment (in years) is defined as the total time on 
study medication between the time of the last dose date and the first dose date plus 26 
days (to account for the long half-life of albiglutide) and then divided by 365.25 
days/year. 
11.5.4.
AE (Event) Density and Incidence Rate
AE density, also referred to as event density, will be calculated as the number of events in 
a given period divided by the total person time on treatment (in years) of subjects at risk 
at the beginning of the same period. The incidence rate for an AE will be calculated as 
the number of subjects experiencing that AE within a given period divided by the total 
person time on treatment (in years) of subjects at risk at the beginning of the same period.
To enhance the data presentation and to aid comparison between treatment groupings, all
AE densities and all incidence rates of AEs will be presented per 100 person-years (by 
multiplying the above defined statistics by 100).


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11.6.
Appendix 6: Premature Withdrawals & Handling of Missing 
Data
11.6.1.
Premature Withdrawal 
The reasons for subjects not completing the treatment period will be recorded in the 
eCRF. Subjects who discontinue active participation in the study will no longer receive 
the randomized study treatment. Immediately upon discontinuation from active 
participation in this study, these subjects should complete the early withdrawal 
assessments and return 8 weeks later for the follow-up assessments.
The reasons for subjects not completing the study will be also recorded in the eCRF. 
Subjects who are withdrawn will not be replaced.
11.6.2.
Missing Date Imputation
In general, partial dates will be imputed as follows:
A partial event start date, partial start dates of prior and concomitant medications or 
partial diagnosis date will be assumed to be the earliest possible date consistent with the 
partial date. 
o
If year is missing, the year will be assumed to be the year part of informed 
consent date of that subject; 
o
If month is missing, the month will be assumed to be January; 
o
If day is missing, it will be assumed to be the first day of the month. 
o
In the case of a completely missing start date, the start date will be assumed to be 
prior to date of the first administration of study drug. 
Partial event or medication stop dates will be assumed to be the latest possible date 
consistent with the partial date.
o
If month is missing, it will be assumed to be December; 
o
If day is missing, it will be assumed to be the last day of the month. 
o
In the case of completely missing stop date, the stop date will be assumed to be 
after the date of the last study visit; the event or medication are considered as 
ongoing. 
For AE date imputation this rule will be followed but will be more conservative in nature 
consistent with the therapy phase (see Appendix 4: Treatment Periods for details).
Since only the year of birth is recorded for subjects in this study, the age of the subjects 
for analysis purposes is calculated using June 30 of the birth year as the imputed subject 
birth date.


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11.6.3.
Handling of Missing Data
11.6.3.1.
Impact of Missing Data on Primary Endpoint
Missing data, in the context of the primary analysis at Week 26, refer to those cases
where the Week 26 HbA1c value is not available or was not collected or subject is lost to 
follow-up or withdraws consent. Missing data will be imputed in the primary MMRM 
analysis. To avoid bias in non-inferiority trials due to missing data, special attention will 
be paid to the handling of missing data in statistical analysis. Although, it is expected that 
the pattern of missing data will be similar in both treatment arms given that the treatment 
arms are the same drug but different formulations and it is expected that the impact of 
missing data on the primary endpoint to be minimal. Imputation under the non-inferiority 
null hypothesis [Koch, 2008] for all missing data for the primary analysis at Week 26 will 
be implemented.
11.6.3.2.
Extent of Missing Primary Analysis Data
Missing data is expected to arise mainly from subjects missing complete visits. The
amount of missing data for those baseline covariates included in the statistical analysis is
expected to be none or at worst minimal. If it should occur, that subject will effectively
be lost to analysis. Missing data for HbA1c between two non-missing visits will be
considered missing at random (intermediate missing data). 
In this study, subjects who withdraw from treatment will stay in the study. In the eCRF, 
the reason for treatment discontinuation and the reason for withdrawal from the study are 
collected separately. Whenever the HbA1c value at Week 26 is missing (end of the 
study), the reason can be determined based on available data in these two locations. The 
reason for missing data can be classified as lost to follow-up or withdrawal of consent or 
investigator discretion.
11.6.3.3.
Reasons for Withdrawal
Reasons for withdrawal from the study are lost to follow-up or withdrawal consent or 
investigator discretion. All subjects who discontinuation from investigational product due 
to the reason listed under protocol Section 5.5 will remain in the study and efficacy and 
safety data will be collected.
11.6.3.4.
Sensitivity Analysis Under Missing Not At Random (MNAR)
The impact of missing data will be explored, as outlined below, for the ITT Analysis
Population only.
Examination of Missing Data Patterns
It is expected that the pattern of missing data will be similar in both treatment groups 
given the each treatment group is using the same drug but different formula.


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To examine the nature of missing data, cohorts of subjects will be defined based on the 
scheduled assessments (HbA1c change from baseline) that were completed at Weeks 1, 4, 
8, 12, 16, 20, and 26.

Subjects who have week 1 assessment only

Subjects who have assessments up to and including Week 4 only

Subjects who have assessments up to and including Week 8 only

Subjects who have assessments up to and including Week 12 only

Subjects who have assessments up to and including Week 16 only

Subjects who have assessments up to and including Week 20 only

Subjects who have assessments up to and including Week 26.
The number and percentage of subjects on each treatment in the 7 cohorts defined here 
will be tabulated. Graphical methods will be used to examine changes from baseline over 
time to assess the pattern of outcomes prior to withdrawal.
Sensitivity Analyses 
The sensitivity of the results of analysis to the method of handling missing values will be 
investigated, especially if the number of missing values is substantial or if the 
characteristics of missing values differ between treatment groups.
To assess the impact of subjects who discontinued investigational product and stayed in 
the study; exclusion of data after treatment discontinuation may also be performed if a 
significant number of subjects discontinue study medication prior to Week 26. On 
treatment data will be analyzed using the same imputation/MMRM model as described in 
Section 7.1.1.1. The imputation will be performed for missing value at Week 26 due to 
any reason and also available value at Week 26, but off-treatment.
Sensitivity analyses using a different type of multiple imputation method will be 
conducted. Firstly, missing data between two non-missing time points (i.e. intermittent 
missing data) will be considered missing at random (MAR). Secondly, missing data after 
the last available assessment due to any reasons (i.e. monotone missing data) will be 
imputed using last mean carried forward (LMCF), that is Missing Not At Random 
(MNAR) (Carpenter and Kenward, 2013). Thirdly, this approach assumes that a constant 
rate of increase in HbA1c change from Baseline is experienced by subjects following 
withdrawal from the study. The imputed values based on LMCF will be then updated 
with an added delta using the following rates of HbA1c increase: 0%/month, 
0.1%/month, and 0.2%/month to explore the potential impact as in a tipping-point 
analysis. For each treatment group, these 3 rates will be assumed, resulting in 9 scenarios. 
The resulting treatment differences and associated P-values for non-inferiority will be 
tabulated against the varying rates of HbA1c increase. This estimand is one where those 
who withdraw are assumed to revert to an unstable treatment regimen with an increasing 
rate of HbA1c. For each imputation data set, an analysis of variance (ANCOVA) will be 
carried using Week 26 data, both actual and imputed, using the same covariates as in the 
primary analysis. Contrasts of interest will be estimated and then combined across 


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imputations using standard multiple imputation rules. The details of implementing this 
multiple imputation approach using delta method in combination with LMCF are the 
following:

Step 1: Multiple Imputation under MAR (K=100 times)
o Run PROC MI for all subjects BY treatment group (specifying the options 
chain=multiple in the MCMC statement). 
o As a result 100 sets of mean vectors (µ) and variance-covariance matrices 
(∑) for each treatment group are simulated from the posterior distribution.
o Each of the above 100 simulated parameter sets leads to a separate 
imputed dataset, in which the missing values (Y2) for each subject are 
replaced by values drawn randomly from their conditional distribution 
given the observed values (Y1). This condition distribution (Y2/Y1) is 
multinomial with mean µ2 + ∑21 ∑11-1 (Y1 - µ1) and variance-covariance 
matrix ∑22 - ∑21 ∑11-1 ∑12. So, 100 imputed datasets are generated.

Step 2: Multiple Imputation using LMCF (K=100 times)
o For each imputed dataset from Step 1, update the imputed values (post-last 
observation) as follows:
For each subject per treatment group, if there are any imputed 
values after the last observation (Yp, imp), first split the simulated 
mean vector (µ) into three parts: µb (prior to last obs), µlast (last 
obs) and µp (post last obs) and then update these imputed values 
as Y*p, imp=( Yp, imp - µp + µlast). Repeat for all subjects and 
for both treatment groups.
o Repeat for the 100 imputed datasets from Step 1.

Step 3: Multiple Imputation using Delta method (K=100 times)
o Calculate delta value for each subject at each visit post-last observation

Let 1  and 2 be the rates of HbA1c increase per month after the 
last observation for the liquid and lyophilized treatment group, 
respectively.

Let be the length of time between visits. Also, consider 1 
month=4 weeks and determine using the visit week values. For 
example, time between visits Week 16 and Week 20 is 4 weeks 
(i.e. 1 month) and time between visits Week 16 and Week 26 is 10 
weeks (i.e. 10/4=2.5 months). 

For each subject and each visit post-last observation, a delta value 
will be derived according to the treatment group the subject was 
randomized to and time between the last observation visit and the 
present visit (). If the subject belongs to the liquid treatment 
group, the delta value = 1 x /4; if the subject belongs to the 
lyophilized treatment group, the delta value = 2 x /4.
o
For each updated imputed dataset from Step 2 increase the imputed values 
post-last observation by the corresponding delta values (per subject per 
visit post-last observation).
o
Repeat for the 100 imputed datasets from Step 2


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
Step 4: Repeat Step 1, Step 2 and Step 3 for 9 scenarios based on 3 different rates 
of HbA1c increase for each treatment group (i.e. 1, 2=0/month , 0.1/month and 
0.2/month) 

Step 5: For each scenario, apply ANCOVA analysis at Week 26 for each of the 
100 imputed dataset and save the difference in LSmeans between treatment group 
and the associated standard error from each of the 100 analyses.

Step 6: For each scenario, combine the 100 set of analysis results using Rubin's 
rules (Rubin, 1987) via SAS PROC MIANALYZE. The treatment differences, 
confidence intervals and p-values will be estimated by MODELEFFECTS and 
STDERR statement. Use the degrees of freedom (EDF) you would have if the 
dataset were complete.
11.6.3.5.
Sensitivity Analysis for Potential Data Fabrication
In case where there are data integrity issues, that would impact the outcome of the trial 
results, we may perform a sensitivity analysis by excluding certain sites from the primary 
analysis. 


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11.7.
Appendix 7: Values of Potential Clinical Importance
11.7.1.
Laboratory
Hematology
Laboratory 
Test
Units
Change from Baseline of 
Potential Clinical Concern 
Potential Clinical Concern 
Value 
Basophils
GI/L
None
None
Eosinophils
GI/L
None
None
Hematocrit
1
>0.1 decrease
>0.05 below LLN
>0.04 above ULN
Hemoglobin
g/L
>25 g/L decrease
>20 g/L below LLN 
>10 g/L above ULN
Lymphocytes
GI/L
None
<0.5 x LLN
Monocytes
GI/L
None
None
Neutrophils
GI/L
None
<1 GI/L
Neutrophil 
Bands
GI/L
None
None
Platelets
GI/L
None
<80 GI/L
>500 GI/L
Red Blood Cell 
Count
TI/L
None
None
Segmented  
Neutrophils
GI/L
None
<0.5 x LLN
White Blood Cell 
Count
GI/L
None
>1 GI/L below LLN 
>5 GI/L above ULN
Chemistry
Laboratory 
Test
Units
Change from Baseline of 
Potential Clinical Concern  
Potential Clinical Concern 
Value 
Albumin
g/L
None
>5 g/L above ULN or below LLN
Alkaline 
Phosphatase 
U/L
None
>3 x ULN
ALT
U/L
None
>3 x ULN
AST
U/L
None
>3 x ULN
Bicarbonate 
(Carbon Dioxide 
Content)
mmol/L
None
<16 mmol/L
> 40 mmol/L
Blood Urea 
Nitrogen
mmol/L
None
>2 x ULN
Calcitonin
pmol/L
None
>100


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Chemistry
Laboratory 
Test
Units
Change from Baseline of 
Potential Clinical Concern  
Potential Clinical Concern 
Value 
Calcium
mmol/L
None
<1.8 mmol/L
>3.0 mmol/L
Chloride
mmol/L
None
None
Creatinine 
umol/L
None
>159 umol/L
Direct Bilirubin
umol/L
None
>1.35 x ULN
Gamma 
Glutamyl 
Transferase
U/L
None
>3 x ULN
Glucose 
(fasting) 
mmol/L
None
<3 mmol/L
>22 mmol/L
Potassium
mmol/L
None
>0.5 mmol/L below LLN 
>1.0 mmol/L above ULN
Sodium
mmol/L
None
>5 mmol/L above ULN or below 
LLN
Total Bilirubin 
umol/L
None
>1.5 x ULN
Total Protein
g/L
None
>15 g/L above ULN or below 
LLN
Uric acid
umol/L
None
>654 umol/L
Free Fatty Acids
mmol/L
None
None
HDL Cholesterol
mmol/L
None
None
LDL Cholesterol
mmol/L
None
None
Triglycerides
mmol/L
None
> 9.04 mmol/L
Total 
Cholesterol
mmol/L
None
None
Liver Function Tests


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Liver Function Tests
Laboratory Test
Potential Clinical Concern Value     
ALT
≥ 2 x ULN
≥ 3 x ULN
≥ 5 x ULN
≥ 8 x ULN
≥ 10 x ULN
≥ 3 x ULN and Total Bilirubin ≥ 2 x ULN
AST
≥ 2 x ULN
≥ 3 x ULN
≥ 5 x ULN
≥ 8 x ULN
≥ 10 x ULN
≥ 3 x ULN and Total Bilirubin ≥ 2 x ULN
Total Bilirubin
≥ 1.5 x ULN
≥ 2 x ULN
≥ 3 x ULN
≥ 5 x ULN
≥ 8 x ULN
≥ 10 x ULN
11.7.2.
Vital Signs
Parameter
Units
Change from Baseline of 
Potential Clinical Concern  
Potential Clinical 
Concern Value 
Systolic BP
mmHg
Decrease >30 mmHg 
Increase >30 mmHg
<100 mmHg
>170 mmHg
Diastolic BP
mmHg
Decrease >30 mmHg 
Increase >30 mmHg
<50 mmHg
>110 mmHg 
Heart rate
bpm
Decrease >30 bpm 
Increase >30 bpm 
<50 bpm
> 120 bpm
11.7.3.
ECG
Parameter
Units
Change from Baseline of Potential Clinical 
Concern  
Potential Clinical 
Concern Value 


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Heart Rate
bpm
None
Supine: < 50 or > 120
QRS interval
msec
Increase of > 25% when baseline QRS >100 msec 
Increase of > 50% when baseline QRS 100 msec
>200 msec 
QTcF 
msec
≥ 60 msec
≥500 msec
PR Interval
msec
Increase of > 25% when baseline PR >200 msec
Increase of > 50% when baseline PR 200 msec
>300 msec


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11.8.
Appendix 8: Multicenter Studies
11.8.1.
Definition of Geographic Region
Clinical sites will be clustered by geographic region since the number of subjects per 
clinical site is expected to be rather small. Geographic regions will be defined based on 
geographic proximity, similarity of medical practice in diabetes, and number of subjects 
per region. Subjects per region will be constrained such that the region with the largest 
sample size is no more than 3 times that of the region with the smallest sample size. The 
clustering will be finalized after clinical site selection and randomization are complete. 

Final classification of geographic region
Region
State
Investigational Site
USA - North
New York, 
Pennsylvania, Ohio, 
Indiana, Illinois, 
Michigan, Missouri, 
Nebraska, Kansas
USA – South Atlantic
North Carolina, South 
Carolina, Georgia, 
Florida
USA – South Central
Kentucky, Alabama, 
Arkansas, Louisiana, 
Texas
USA - West
Idaho, Colorado, New 
Mexico, Arizona, Utah, 
Nevada, Washington, 
California
PPD


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11.9.
Appendix 9: Examination of Covariates, Subgroups & Other 
Strata
11.9.1.
Strata and Covariates
The randomization for this study is stratified by the following baseline characteristics:

Age at randomization (<65 years versus ≥65 years)

Weight at Screening (<90 or >=90 kg)

Background antidiabetic therapy (diet and exercise or stable dose of metformin)
The primary analysis of HbA1c change from baseline will use a mixed-effect model with 
repeated measures (MMRM), which includes HbA1c change from baseline at all post-
baseline visits as dependent variables; treatment, region, age category, weight category, 
backgroup antidiabetic therapy, visit week, treatment-by-visit interaction as fixed effects; 
baseline HbA1c as a continuous covariate; and subject as a random effect.
11.9.2.
Examination of Subgroups
The primary efficacy endpoint will be analyzed for the following subgroups using a 
MMRM model described in Section 7. 

Baseline HbA1c (< 8% or >=8%)

Region (USA – North, USA – South Atlantic, USA – South Central, USA -
West)

Age at randomization (<65 or >=65 years)

Weight at Screening (<90 or >=90 kg)

Background antidiabetic therapy (diet and exercise or stable dose of metformin)

Gender (male or female)

Race (white or non-white)

Ethnicity (Hispanic or non-hispanic)

Duration of diabetes category (<5, 5 to 10 or >10 years) 


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11.10.
Appendix 10: Multiple Comparisons & Multiplicity
11.10.1.
Handling of Multiple Comparisons & Multiplicity
Not applicable.


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11.11.
Appendix 11: Model Checking and Diagnostics for 
Statistical Analyses
11.11.1.
Model Checking and Diagnostics for Statistical Analyses
1. Example SAS code for the primary efficacy analysis with imputation
Step 1a: Transpose the data horizontally and then impute data assuming missing at 
random (EFFIM)
PROC MI DATA= EFF OUT= EFFIM NIMPUTE=100 SEED=4408572;
   BY TRT01PN;
   MCMC CHAIN=multiple;
   VAR BASE CHG_W1 CHG_W4 CHG_W8 CHG_W12 CHG_W16 CHG_W20 CHG_W26;
   RUN;
Note: need to remove all imputed values before Week 26 and retain imputed values at 
Week 26 only.
Step 1b: Add 0.4 to the imputed value at Week 26 in the liquid product arm and transpose 
data in vertical structure (EFFIM2)
Step 2: Exclude HbA1c change from baseline at Week 1 and perform MMRM for each 
imputed dataset
Ods output SLICES=SLICELSM SLICEDIFFS=SLICEDIFF;
PROC MIXED DATA= EFFIM ; 
  BY _imputation_;
   CLASS USUBJID REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN; 
   MODEL CHG= BASE REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN 
TRT01PN*AVISITN BASE*AVISITN/ DDFM=KR; 
   REPEATED AVISITN/SUB=USUBJID TYPE=UN;
   SLICE TRT01PN*AVISITN/sliceby(AVISITN=’26’) means pdiff cl cov;
RUN;
Step 3: Combine results using PROC MIANALYZE
PROC SORT DATA=SLICELSM; BY TRT01PN IMPUTATION; RUN;
PROC MIANALYZE DATA=SLICELSM EDF=CDF*;
BY TRT01PN;
MODELEFFECTS ESTIMATE;
STDERR STDERR;
RUN;
PROC MIANALYZE DATA=SLICEDIFF;
MODELEFFECTS ESTIMATE;
STDERR STDERR;
RUN;
*CDF=complete-data degrees of freedom. This is used to calculate the 
adjusted degrees of freedom for the combined results.


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2. Example SAS code for the by-subgroup analysis of the primary endpoint with 
imputation
Follow the same steps as for the example SAS code for the primary analysis except in the 
step 2 additional interaction terms need to be added.
Subgroup variable: Baseline HbA1c <8% or >=8%
ods output SLICES=SLICELSM1 SLICEDIFFS=SLICEDIFF1;
PROC MIXED DATA= EFFIM; 
   BY imputation;
   CLASS USUBJID REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN HBGR1; 
   MODEL CHG= HBGR1 REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN 
TRT01PN*AVISITN HBGR1*TRT01PN HBGR1*AVISITN
        HBGR1*TRT01PN*AVISITN/ DDFM=KR; 
   REPEATED AVISITN/SUB=USUBJID TYPE=UN;
   SLICE HBGR1*TRT01PN*AVISITN/sliceby(AVISITN=’26’) means pdiff cl
cov;
RUN;
Subgroup variable: Baseline Weight <90 or >=90 kg
ods output SLICES=SLICELSM2 SLICEDIFFS=SLICEDIFF2;
PROC MIXED DATA= EFFIM; 
   BY imputation;
   CLASS USUBJID REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN; 
   MODEL CHG= BASE REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN 
TRT01PN*AVISITN BASE*AVISITN WGTGR1*TRT01PN WGTGR1*AVISITN
        WGTGR1*TRT01PN*AVISITN/ DDFM=KR; 
   REPEATED AVISITN/SUB=USUBJID TYPE=UN;
   SLICE WGTGR1*TRT01PN*AVISITN/sliceby(AVISITN=’26’) means pdiff cl
cov;
RUN;
3. Example SAS code for the secondary efficacy analyses using MMRM without 
imputation
PROC MIXED DATA= INDATA ; 
   CLASS USUBJID REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN; 
   MODEL CHG= BASE REGION WGTGR1 AGEGR1 PRIORDTX TRT01PN AVISITN 
TRT01PN*AVISITN BASE*AVISITN/ DDFM=KR; 
   REPEATED AVISITN/SUB=USUBJID TYPE=UN;
   SLICE TRT01PN*AVISITN/slice=AVISITN means pdiff cl cov;
RUN;


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11.12.
Appendix 12: Sample Size Considerations 
11.12.1.
Sample Size Assumptions
This study will randomly assign approximately 150 subjects to each of the 2 treatment 
groups (liquid drug product and lyophilized drug product) in a 1:1 ratio, for a total of 
approximately 300 subjects. Eligible subjects will be stratified by age (<65 or ≥65 years 
of age), weight (<90 kg or ≥90 kg), and background antidiabetic therapy (diet and 
exercise or stable dose of metformin).
With 133 subjects in each of the 2 treatment groups, the study will provide 90% power to 
demonstrate non-inferiority for HbA1c change from baseline, assuming a non-inferiority 
margin of 0.4%, an expected treatment group difference of 0.0%, and a common standard 
deviation of 1%, using a 2-sample, 1-sided t test with significance level of 0.025. Power 
was calculated using PASS [Hintze, 2013]. Assuming that 13% of subjects will be 
withdrawn early or will be lost to follow-up; therefore, approximately 150 subjects will 
be randomized in each treatment group. 
The non-inferiority margin of 0.40 was selected based on the expected effect of the 
albiglutide lyophilized drug product as active control. Results from two HARMONY 
Phase III studies (subset of GLP112756 and GLP112753) for the comparison of the
control albiglutide lyophilized drug product versus placebo were used in selecting the 
non-inferiority margin. The two studies are similar to the current study in terms of the 
population and the design; subjects were either on diet and exercise or metformin 
background therapy and received 30 mg of albiglutide then up-titrated to 50 mg 
albiglutide. The 95% confidence interval from the 2 Harmony studies for HbA1c change 
from baseline at week 24 for albiglutide lyophilized drug product difference from placebo
is ( -1.04, -0.75). The conservative effect in terms of the difference from placebo for 
HbA1c change from baseline at Week 24 for albiglutide lyophilized drug product versus 
placebo is 0.75% (M1 =0.75%, as defined in Guidance for Industry: Non-Inferiority
Clinical Trials [FDA, 2010]). M2, calculated as 50% of M1 is 0.375 (approximately 
0.4).The margin of 0.40% that should be met in this trial will preserve at least 45% of the 
effect of the comparator and it is below M1.
11.12.2.
Sample Size Sensitivity
The following Figure illustrates the power versus standard deviation of 0.7, 0.8, 0.9, 1.0, 
1.1, and 1.2 to reject the null hypothesis of inferiority for HbA1c change from baseline, 
assuming a non-inferiority margin of 0.4%, an expected treatment group difference of 
0.0%, and a sample size of 133 per treatment group, using a 2-sample, 1-sided t- test with 
a significance level of 0.025.


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11.12.3.
Sample Size Re-estimation or Adjustment
No sample size re-estimation is planned for this study.


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11.13.
Appendix 13 – Abbreviations & Trade Marks
Abbreviations
ADA
American Diabetes Association
AE
adverse event
ALT (SGPT)
alanine aminotransferase (serum glutamic pyruvic 
transaminase)
AST (SGOT)
aspartate aminotransferase (serum glutamic oxaloacetic 
transaminase)
BMI
body mass index
BUN
blood urea nitrogen
CI
confidence interval
CONSORT
Consolidated Standards of Reporting Trials
CPK
creatine phosphokinase
CV
cardiovascular
DCC
dual chamber cartridge
DNA
deoxyribonucleic acid
ECG
electrocardiogram
eCRF
electronic case report form
eGFR
estimated glomerular filtration rate
ELISA
enzyme-linked immunosorbent assay
EMA
European Medicines Agency
FDA
US Food and Drug Administration
FFA
free fatty acids
FPG
fasting plasma glucose
FRP
females of reproductive potential
FSH
follicle stimulating hormone
GCP
Good Clinical Practice
GCSP
Global Clinical Safety and Pharmacovigilance
GGT
gamma glutamyl transferase
GI
gastrointestinal
GLP-1
glucagon-like peptide-1
GSK
GlaxoSmithKline
HA
human albumin
HbA1c
glycated hemoglobin
HBcAb
hepatitis B core antibody 
HBsAg
hepatitis B surface antigen
HIV
human immunodeficiency virus
hCG
human chorionic gonadotrophin
HDL-c
high density lipoproteins
HRP
horseradish peroxidase
HRT
hormone replacement therapy
IB
Investigator’s Brochure
ICH
International Conference on Harmonization


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IEC
Independent Ethics Committee
INR
international normal range
IP
investigational product
IRB
Institutional Review Board
ISRs
injection site reactions
ITT
intent-to-treat
IVRS
Interactive Voice Response System
LDH
lactate dehydrogenase
LDL-c
low density lipoproteins; 
LMCF
last mean carried forward
K2EDTA
di-potassium ethylenediaminetetraacetic acid
MACE
major adverse cardiovascular event
MAR
missing at random
MCH
mean corpuscular hemoglobin
MCV
mean corpuscular volume
MDRD
Modification of Diet in Renal Disease
MedDRA
Medical Dictionary for Regulatory Activities
MEN-2
multiple endocrine neoplasia type 2
MI
myocardial infarction
MMRM
mixed-effect model with repeated measures
MNAR
missing not at random
MSDS
Material Safety Data Sheet
MTC
medullary thyroid cancer
OC RDC
Oracle Clinical Remote Data Capture
PAC
Pancreatitis Adjudication Committee
PD
pharmacodynamics
PK
pharmacokinetics
PP
per protocol
PTS-DPMK
Platform Technologies and Science-Drug Metabolism and 
Pharmacokinetics
RAP
Reporting Analysis Plan
RBC
red blood cell
RNA
ribonucleic acid
s.c.
subcutaneous
SAC
Statistical Analysis Complete
SAE
serious adverse event
SmPC
Summary of Product Characteristics
SRM
Study Reference Manual
SU
sulfonylureas
T2DM
type 2 diabetes mellitus
TSH
thyroid stimulating hormone
ULN
upper limit of normal range
WBC
white blood cell
WCBP
women of child bearing potential


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Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
MedDRA


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11.14.
Appendix 14: List of Data Displays
11.14.1.
Data Display Numbering
The following numbering will be applied for RAP generated displays:
Section
Tables
Figures
Study Population
1.01 to 1.43
N/A
Efficacy
2.01 to 2.32
2.01 to 2.14
Safety
3.01 to 3.352
3.01 to 3.61
Section
Listings
ICH Listings
1 to 35
Other Listings
101 to 154


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11.14.2.
Study Population Tables
Study Population Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Disposition
1.1.
All 
Randomized 
Subjects
Subject Disposition
1.2.
All Subjects 
Screened
Reasons for Screening Failures
1.3.
All 
Randomized 
Subjects
Reasons for Withdrawal from Study
1.4.
All 
Randomized 
Subjects
Reasons for Discontinuing Study Treatment
1.5.
All 
Randomized 
Subjects
Subject Status by Visit
1.6.
All 
Randomized 
Subjects
Subjects Randomized across Sites
1.7.
All 
Randomized 
Subjects
Inclusion/Exclusion Criteria Deviations
Protocol Deviation


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Study Population Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.8.
All 
Randomized 
Subjects
Significant Protocol Deviations
Demographics and Baseline Characteristics
1.9.
[Safety]
Demographics and Baseline Characteristics
1.10.
All 
Randomized 
Subjects
Geographic Ancestry
1.11.
Safety
Substance Use
Medical History
1.21.
Safety
Medical and Family History Status
1.22.
Safety
Current and/or Past Cardiovascular Medical History
1.23.
Safety
Current and/or Past Diabetes Related Conditions
1.24.
Safety
Duration of Diabetes Disease History
1.25.
Safety
Current and/or Past Medical/Surgical Procedure History
1.26.
Safety
Current and/or Past Gastrointestinal Medical Conditions
1.27.
Safety
Current and/or Past Cancer History
1.28.
Safety
Current and/or Past Pneumonia Medical History
1.29.
Safety
Current and/or Past Skin Medical Conditions
1.30.
Safety
Current and/or Past Thyroid Medical History
1.31.
Safety
Current and/or Past Other Medical History
Prior and Concomitant Medications
1.41.
Safety
Prior Medications


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Study Population Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
1.42.
Safety
Concomitant Medications
1.43.
Safety
Post-therapy Medications


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11.14.3.
Efficacy Tables
Efficacy: Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
HbA1c
2.1.
ITT
Primary Analysis - Analysis of Change from Baseline in HbA1c 
(%) at Week 26 — With Imputation
2.2.
ITT
Statistical Output Supporting the Primary Analysis of Change 
from Baseline in HbA1c (%) at Week 26
2.3.
ITT
Supportive Analysis 1 - Analysis of Change from Baseline in 
HbA1c (%) at Week 26 — Without Imputation
2.4.
ITT
Statistical Output Supporting the Supportive Analysis 1 of 
Change from Baseline in HbA1c (%) at Week 26 — Without 
Imputation
2.5.
ITT
Supportive Analysis 2 - Analysis of Change from Baseline in 
HbA1c (%) at Week 26 — Without Imputation and Excluding 
Data after Hyperglycemia Rescue and discontinuation from
study treatment
2.6.
ITT
Statistical Output Supporting the Supportive Analysis 2 of 
Change from Baseline in HbA1c (%) at Week 26 — Without 
Imputation and Excluding Data after Hyperglycemia Rescue and 
discontinuation from study treatment
2.7.
PP
Supportive Analysis 3 — Per Protocol Analysis of Change from 
Baseline in HbA1c (%) at Week 26 — Without Imputation
2.8.
PP
Statistical Output Supporting the Supportive Analysis 3 of Per 
Protocol Analysis of Change from Baseline in HbA1c (%) at 
Week 26 — Without Imputation


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Efficacy: Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.9.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Baseline HbA1c Category — With Imputation
2.10.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Age Category at Randomization — With 
Imputation
2.11.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Region — With Imputation
2.12.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Weight Category at Randomization — With 
Imputation
2.13.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Background Antidiabetic Therapy — With 
Imputation
2.14.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Gender — With Imputation
2.15.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Race — With Imputation
2.16.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Ethnicity — With Imputation
2.17.
ITT
Subgroup analysis: Analysis of Change from Baseline in HbA1c 
(%) at Week 26 by Duration of Diabetes Category — With 
Imputation
2.18.
ITT
Sensitivity Analysis 1 - Analysis of Change from Baseline in 
HbA1c (%) at Week 26 — Excluding Data after Treatment 
Discontinuation and With Imputation


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Efficacy: Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
2.19.
ITT
Sensitivity Analysis 2: Tipping Point Analysis of Change from 
Baseline in HbA1c (%) at Week 26 — With Imputation
2.20.
ITT
Examination of the Pattern of Missing HbA1c Values
2.21.
ITT
Summary Statistics for HbA1c (%) by Visit
2.22.
ITT
Analysis of Change from Baseline in HbA1c (%) over Time
FPG
2.31.
ITT
Summary Statistics for Change from Baseline in Fasting Plasma 
Glucose (mmol/L) by Visit
2.32.
ITT
Analysis of Change from Baseline in Fasting Plasma Glucose 
(mmol/L) by Visit


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11.14.4.
Efficacy Figures
Efficacy: Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
HbA1c
2.1.
ITT
Line Graph of Mean (+/- SE) of HbA1c (%) by Treatment Group 
and Visit
2.2.
ITT
Line Graph of Mean (+/- SE) of Change from Baseline in HbA1c 
(%) by Treatment Group and Visit
2.3.
ITT
Line Graph of LS Mean (+/- SE) of Change from Baseline in 
HbA1c (%) by Treat Group and Visit — Without Imputation
2.4.
ITT
Model-adjusted Change from Baseline in HbA1c (%) for 
Albiglutide liquid vs. Albiglutide lyophilized and 95% CI at Week 
26 — With Imputation
2.5.
ITT
Line Graph of Mean of Change from Baseline in HbA1c (%) by 
Missing Data Patterns and Treatment
2.6.
ITT
Model-adjusted Change from Baseline in HbA1c (%) for 
Albiglutide liquid vs. Albiglutide lyophilized and 95% CI at Week 
26 — Supportive Analysis 1 Without Imputation
2.7.
ITT
Model-adjusted Change from Baseline in HbA1c (%) for 
Albiglutide liquid vs. Albiglutide lyophilized and 95% CI at Week 
26 — Supportive Analysis 2 Without Imputation and Excluding 
Data after Hyperglycemia Rescue and Discontinuation from 
Study Treatment
2.8.
PP
Model-adjusted Change from Baseline in HbA1c (%) for 
Albiglutide liquid vs. Albiglutide lyophilized and 95% CI at Week 
26 — Supportive Analysis 3 of Per Protocol Analysis Without 
Imputation


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Efficacy: Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
FPG
2.11.
ITT
Line Graph of Mean (+/- SE) of Fasting Plasma Glucose 
(mmol/L) by Treatment Group and Visit
2.12.
ITT
Line Graph of Mean (+/- SE) of Change from Baseline in Fasting 
Plasma Glucose (mmol/L) by Treatment Group and Visit
2.13.
ITT
Line Graph of LS Mean (+/- SE) of Change from Baseline in 
Fasting Plasma Glucose (mmol/L) by Treatment Group and Visit 
— Without Imputation
2.14.
ITT
Model-adjusted Change from Baseline in Fasting Plasma 
Glucose (mmol/L) for Albiglutide liquid vs. Albiglutide lyophilized 
and 95% CI at Week 26 — Without Imputation


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11.14.5.
Safety Tables
Safety : Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Exposure and Compliance
3.1.
Safety
Exposure to Treatment
3.2.
Safety
Treatment Compliance
[Adverse Events]
3.11.
Safety
Overview of Adverse Events
3.12.
Safety
All On-therapy and Post-therapy Adverse Events
3.13.
Safety
Pre-therapy Adverse Events
3.14.
Safety
On-therapy Adverse Events
3.15.
Safety
Most Common On-therapy Adverse Events
3.16.
Safety
Post-therapy Adverse Events
3.17.
Safety
On-Therapy Adverse Events and the Information on Relation to 
Treatment
3.18.
Safety
On-therapy Adverse Events by Time of Onset with 12-Weeks 
Intervals
3.19.
Safety
On-therapy Non-serious Adverse Events
3.20.
Safety
On-Therapy Non-serious Adverse Events with Incidence of 
Preferred Term >2% in Any Treatment Group and the 
Information on Relation to Treatment
3.21.
Safety
On-therapy and Post-therapy Adverse Events Related to Study 
Treatment
3.22.
Safety
On-therapy Treatment-related Adverse Events
3.23.
Safety
Post-therapy Treatment-related Adverse Events


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Safety : Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.24.
Safety
On-therapy and Post-therapy Treatment-related Adverse Events
3.31.
Safety
Overall Summary of On-therapy and Post-therapy Adverse 
Events by Maximum Intensity
3.32.
Safety
On-therapy Adverse Events by Maximum Intensity
3.33.
Safety
Post-therapy Adverse Events by Maximum Intensity
3.34.
Safety
On-therapy and Post-therapy Adverse Events by Maximum 
Intensity
3.41.
Safety
Pre-therapy Serious Adverse Events
3.42.
Safety
On-therapy Serious Adverse Events
3.43.
Safety
On-Therapy Serious Adverse Events and the Information on 
Relation to Treatment
3.44.
Safety
Post-therapy Serious Adverse Events
3.45.
Safety
On-therapy Treatment-related Serious Adverse Events
3.46.
Safety
Post-therapy Treatment-related Serious Adverse Events
3.47.
Safety
On-Therapy Fatal Serious Adverse Events and the Information 
on Relation to Treatment
3.48.
Safety
On-Therapy Non-fatal Serious Adverse Events and the 
Information on Relation to Treatment
3.51.
Safety
On-therapy Adverse Events Leading to Permanent 
Discontinuation of Study Treatment
3.52.
Safety
On-therapy Adverse Events Leading to Withdrawal from Study
Adverse Events of Special Interest
3.61.
Safety
Overview of On-therapy Adverse Events of Special Interest


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Safety : Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.71.
Safety
On-therapy Hypoglycemic Events by SAE Status, Relationship 
to Study Medication, and Withdrawal Status
3.72.
Safety
On-therapy Hypoglycemic Events by Treatment, Symptom, 
Severity, Intervention and Action Taken
3.73.
Safety
On-therapy Hypoglycemic Events by Blood Glucose Level
3.80.
Safety
On-therapy Hypoglycemic Events over Time by Onset Week
3.91.
Safety
On-therapy and Post-therapy Cardiovascular Adverse Events
3.101.
Safety
On-therapy and Post-therapy Thyroid Adverse Events Reported 
by the Investigator
3.102.
Safety
On-therapy and Post-therapy Thyroid Adverse Events Identified 
by a Customized MedDRA Query
3.111.
Safety
Summary of Gastrointestinal Adverse Events
3.112.
Safety
On-therapy Gastrointestinal Adverse Events
3.113.
Safety
On-therapy Serious Gastrointestinal Adverse Events
3.114.
Safety
On-therapy Treatment-related Gastrointestinal Adverse Events
3.115.
Safety
On-therapy Gastrointestinal Adverse Events Leading to 
Permanent Discontinuation of Study Treatment before 
Scheduled End of Treatment Period
3.116.
Safety
On-therapy Gastrointestinal Adverse Events over Time
3.117.
Safety
On-therapy Gastrointestinal Adverse Events by Onset Week
3.118.
Safety
Kaplan-Meier Analysis of Time to First Occurrence of a 
Gastrointestinal Adverse Event
3.119.
Safety
On-therapy Nausea over Time
3.120.
Safety
On-therapy Diarrhea over Time


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Safety : Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.121.
Safety
On-therapy Vomiting over Time
3.122.
Safety
On-therapy Nausea or Vomiting over Time
3.131.
Safety
On-therapy and Post-therapy System Allergic Reactions 
Identified by the Investigator
3.132.
Safety
On-therapy and Post-therapy System Allergic Reactions 
Identified by a Customized MedDRA Query
3.133.
Safety
Kaplan-Meier Analysis of Time to First Occurrence of a Systemic 
Allergic Reaction Reported by the Investigator
3.134.
Safety
Kaplan-Meier Analysis of Time to First Occurrence of a Systemic 
Allergic Reaction Identified by a Customized MedDRA Query
3.141.
Safety
On-therapy and Post-therapy Injection Site Reactions
3.142.
Safety
Kaplan-Meier Analysis of Time to First Occurrence of an 
Injection Site Reaction
3.143.
Safety
On-therapy Injection Site Reaction over Time
3.144.
Safety
Summary Characteristics of On-therapy Injection Site Reactions
3.151.
Safety
On-therpy and Post-therapy Liver Events Identified by a 
Customized MedDRA Query
3.161.
Safety
On-therapy and Post-therapy Pancreatitis and Pancreatic 
Cancer
3.162.
Safety
On-therapy and Post-therapy Adjudicated Pancreatitis Events
3.171.
Safety
On-therapy and Post-therapy Atrial Fibrillation and Atrial Flutter 
Adverse Events
3.181.
Safety
On-therapy and Post-therapy Pneumonia Adverse Events 
Reported by the Investigator


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200952
87
Safety : Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.182.
Safety
On-therapy and Post-therapy Pneumonia Adverse Events 
Identified by a Customized MedDRA Query
3.191.
Safety
On-therapy and Post-therapy Diabetic Retinopathy Adverse 
Events
3.201.
Safety
On-therapy and Post-therapy Appendicitis Adverse Events
3.211.
Safety
On-therapy and Post-therapy Malignant Neoplasm Adverse 
Events Identified by a Customized MedDRA Query
Lab Assessments
3.221.
Safety
Change from Baseline in Hematology by Visit
3.222.
Safety
Change from Baseline in Chemistry by Visit
3.223.
Safety
Hematology Values of Clinical Concern by Visit
3.224.
Safety
Chemistry Values of Clinical Concern by Visit
3.225.
Safety
Liver Function Tests of Clinical Concern by Visit
3.226.
Safety
Shift in Hematology by Visit
3.227.
Safety
Shift in Chemistry by Visit
3.228.
Safety
Urinalysis by Visit
Vital Signs
3.231.
Safety
Change from Baseline in Vital Signs by Visit
3.232.
Safety
Vital Signs of Clinical Concern by Visit
3.233.
Safety
Shift in Vital Signs of Clinical Concern by Visit
[ECG]
3.341.
Safety
Change from Baseline in ECG Values by Visit
3.342.
Safety
ECG Values of Clinical Concern by Visit


CONFIDENTIAL
200952
88
Safety : Tables
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.343.
Safety
Overall ECG Interpretations by Visit
3.344.
Safety
Shift in ECG Values of Clinical Concern from Baseline to Week 
26
3.345.
Safety
ECG QTcF and QTcB Results of Notable Abnormalities at any 
time post-baseli
Immunogenicity
3.351.
Safety
Positive Immunogenicity Results for Anti-Albiglutide Antibody 
Positive Subjects by Visit
3.352.
Safety
Positive Immunogenicity Results for Anti-Albiglutide Antibody 
Positive Subjects by Therapy Phase


CONFIDENTIAL
200952
89
11.14.6.
Safety Figures
Safety : Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Adverse Events of Special Interest 
3.1.
Safety
On-therapy Hypoglycemic Events over Time
3.11.
Safety
On-therapy Gastrointestinal Adverse Events Over Time
3.12.
Safety
On-therapy Nausea Over Time
3.13.
Safety
On-therapy Diarrhea Over Time
3.14.
Safety
On-therapy Vomiting Over Time
3.15.
Safety
On-therapy Nausea or Vomiting Over Time
3.21.
Safety
On-therapy Injection Site Reaction Over Time
Lab
3.31.
Safety
Line Graph of Mean (+/- SE) Results for Hematology 
Parameters
3.32.
Safety
Line Graph of Mean (+/- SE) Results for Chemistry Parameters
3.33.
Safety
Line Graph of Mean (+/- SE) Change from Baseline Results for 
Hematology Parameters
3.34.
Safety
Line Graph of Mean (+/- SE) Change from Baseline Results for 
Chemistry Parameters
Vital Signs
3.41.
Safety
Line Graph of Mean (+/- SE) Results for Vital Sign Parameters
3.42.
Safety
Line Graph of Mean (+/- SE) Change from Baseline Results for 
Vital Sign Parameters
ECG


CONFIDENTIAL
200952
90
Safety : Figures
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
3.51.
Safety
Line Graph of Mean (+/- SE) Results for ECG Parameters
3.52.
Safety
Line Graph of Mean (+/- SE) Change from Baseline Results for 
ECG Parameters
Immunogenicity
3.61.
Safety
Number and Percentage of Subjects with Positive 
Immunogenicity Results for Anti-Albiglutide Antibody Over Time


CONFIDENTIAL
200952
91
11.14.7.
ICH Listings
ICH : Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
Vital Signs
1.
Safety
Vital Signs of Clinical Concern
ECG
2.
Safety
ECG Values of Clinical Concern
Adverse Events and Adverse Events of Special Interest
4.
Safety
Fatal Adverse Events
5.
Safety
Serious Non-fatal Adverse Events
6.
Safety
Adverse Events Leading to Withdrawal from Study
7.
Safety
Adverse Events Leading to Permanent Discontinuation of Study 
Drug
8.
Safety
Hypoglycemic Events
10.
Safety
Cardiovascular Events - Deep Vein Thrombosis/Pulmonary 
Embolism
11.
Safety
Cardiovascular Events - Arrhythmias
12.
Safety
Cardiovascular Events - Myocardial Infarction (MI)/Unstable 
Angina (UA)
13.
Safety
Cardiovascular Events - Cerebrovascular Events/Stroke (CVA) 
and Transient Ischemic Attack (TIA)
14.
Safety
Cardiovascular Events - Congestive Heart Failure
15.
Safety
Cardiovascular Events - Peripheral Arterial Thromboembolism
16.
Safety
Cardiovascular Events - Pulmonary Hypertension


CONFIDENTIAL
200952
92
ICH : Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
17.
Safety
Cardiovascular Events - Coronary Revascularization
18.
Safety
Cardiovascular Events - Peripheral Revascularization
19.
Safety
Cardiovascular Events - Valvulopathy
20.
Safety
Pancreatitis Events
21.
Safety
Thyroid Cancer/Nodules/ Goiter
22.
Safety
Customized MedDRA Query Identified Thyroid Adverse Events
23.
Safety
Systemic Allergic Reactions Reported by the Investigator
24.
Safety
Systemic Allergic Reactions Identified by Customized MedDRA 
Query
25.
Safety
Injection Site Reactions
26.
Safety
Liver Events Identified by a Customized MedDRA Query
27.
Safety
Atrial Fibrillation/Flutter
28.
Safety
Pneumonia Reported by the Investigator
29.
Safety
Pneumonia Reported Identified by a Customized MedDRA 
Query
30.
Safety
Diabetic Retinopathy
31.
Safety
Appendicitis
32.
Safety
Malignant Neoplasm
33.
Safety
Hematology Values of Clinical Concern
34.
Safety
Chemistry Values of Clinical Concern
35.
Safety
Liver Function Test Results of Clinical Concern


CONFIDENTIAL
200952
93
11.14.8.
Non-ICH Listings
Non-ICH : Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
101.
All 
Randomized 
Subjects
Randomization Allocation to Treatment
102.
All 
Randomized 
Subjects
Subject Disposition
103.
All 
Randomized 
Subjects
Reasons for Withdrawal from Study
104.
All 
Randomized 
Subjects
Reasons for Discontinuing Study Treatment
105.
All Subjects 
Screened
Reasons for Screening Failures
106.
All 
Randomized 
Subjects
Subject Visits
107.
All 
Randomized 
Subjects
Inclusion/Exclusion Criteria Deviations
108.
All 
Randomized 
Subjects
Protocol Deviations


CONFIDENTIAL
200952
94
Non-ICH : Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
110.
All 
Randomized 
Subjects
Analysis Populations
111.
Safety
Demographics and Baseline Characteristics
112.
All 
Randomized 
Subjects
Geographic Ancestry
113.
Safety
Substance Use
114.
Safety
Cardiovascular Medical History
115.
Safety
Diabetes Related Conditions
116.
Safety
Diabetes Disease History
117.
Safety
Medical/Surgical Procedure History
118.
Safety
Gastrointestinal Medical Conditions
119.
Safety
Cancer History
120.
Safety
Pneumonia Medical History
121.
Safety
Skin Medical Conditions
122.
Safety
Thyroid Medical History
123.
Safety
Thyroid Cancer History
124.
Safety
History Benign Thyroid Conditions
125.
Safety
Thyroid Cancer Family History
126.
Safety
Pancreatitis Family History
127.
Safety
Pancreatic Cancer Family History
128.
Safety
Other Medical History


CONFIDENTIAL
200952
95
Non-ICH : Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
129.
Safety
Hypersensitivity - Past Medical Conditions
130.
Safety
Prior and Concomitant Medications
131.
Safety
Albiglutide Administration and Compliance
132.
All 
Randomized 
Subjects
HbA1c (%)
133.
All 
Randomized 
Subjects
Stratifying Factors Used in MMRM Models
134.
All 
Randomized 
Subjects
Subgroup Values Used in Subgroup Analyses
135.
All 
Randomized 
Subjects
Fasting Plasma Glucose (mmol/L)
136.
Safety
Adverse Events
138.
Safety
Hematology Laboratory Evaluations
139.
Safety
Chemistry Laboratory Evaluations
140.
Safety
Urinalysis Laboratory Evaluations
142.
Safety
Vital Signs
143.
Safety
ECG Values
144.
Safety
Overall ECG Interpretations
145.
Safety
Pregnancies
146.
Safety
Liver Events Information


CONFIDENTIAL
200952
96
Non-ICH : Listings
No.
Population
IDSL / TST ID / 
Example Shell
Title
Programming Notes
Deliverable 
[Priority]
147.
Safety
Liver Biopsy
148.
Safety
Liver Imaging
149.
Safety
Other Medical/Surgical Procedures
150.
Safety
Other Lab Results at Screening
151.
Safety
Immunogenicity Information: Anti-Albiglutide Antibody
152.
Safety
Listing of Subject Numbers for Individual Adverse events
153.
Safety
Listing of Relationship between System Organ Class and 
Verbatim Text
154.
All 
Randomized 
Subjects
Listing of Subjects for Whom the Treatment Blind was Broken 
During the Study