An Open-label Extension to Study 200952 to Evaluate the Long-term Safety, Tolerability and Pharmacodynamics of Albiglutide Liquid Drug Product in Subjects With Type 2 Diabetes Mellitus
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Sponsor: GlaxoSmithKline

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TITLE PAGE
Division:  Worldwide Development
Information Type: Clinical Protocol
Title:
An Open-label Extension to Study 200952 to Evaluate the Long-
term Safety, Tolerability and Pharmacodynamics of Albiglutide 
Liquid Drug Product in Subjects with Type 2 Diabetes Mellitus
Compound Number:
GSK716155
Development Phase
III/IV
Effective Date:
28-OCT-2015 
Author(s):
 
Copyright 2015 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
 
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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
N/A
N/A
N/A
N/A
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
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
 
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INVESTIGATOR PROTOCOL AGREEMENT PAGE

I confirm agreement to conduct the study in compliance with the protocol.

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 Signature
Date
 
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TABLE OF CONTENTS
PAGE
1.
PROTOCOL SYNOPSIS FOR STUDY 204682........................................................8
2.
INTRODUCTION....................................................................................................10
2.1.
Study Rationale ..........................................................................................10
3.
OBJECTIVE(S) AND ENDPOINT(S) ......................................................................10
4.
STUDY DESIGN ....................................................................................................10
4.1.
Overall Design ............................................................................................10
4.2.
Treatment Arms and Duration.....................................................................11
4.3.
Type and Number of Subjects.....................................................................11
4.4.
Design Justification.....................................................................................11
4.5.
Dose Justification........................................................................................12
4.6.
Benefit:Risk Assessment ............................................................................12
4.6.1.
Risk Assessment .........................................................................13
4.6.2.
Benefit Assessment.....................................................................19
4.6.3.
Overall Benefit:Risk Conclusion...................................................19
5.
SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA .............19
5.1.
Inclusion Criteria.........................................................................................19
5.2.
Exclusion Criteria........................................................................................20
5.3.
Hyperglycemia Rescue...............................................................................21
5.4.
Withdrawal/Stopping Criteria.......................................................................21
5.4.1.
Liver Chemistry Stopping Criteria ................................................23
5.4.1.1.
Study Treatment Restart or Rechallenge....................24
5.4.2.
QTc Stopping Criteria ..................................................................24
5.5.
Subject and Study Completion....................................................................25
6.
STUDY TREATMENT ............................................................................................25
6.1.
Investigational Product and Other Study Treatment....................................25
6.2.
Treatment Assignment................................................................................25
6.3.
Planned Dose Adjustments.........................................................................26
6.4.
Blinding.......................................................................................................26
6.5.
Packaging and Labeling..............................................................................26
6.6.
Preparation/Handling/Storage/Accountability..............................................26
6.7.
Compliance with Study Treatment Administration.......................................27
6.8.
Treatment of Study Treatment Overdose....................................................27
6.9.
Treatment after the End of the Study ..........................................................27
6.10.
Concomitant Medications and Non-Drug Therapies....................................27
6.10.1.
Permitted Medications and Non-Drug Therapies..........................28
6.10.2.
Prohibited Medications and Non-Drug Therapies.........................28
7.
STUDY ASSESSMENTS AND PROCEDURES .....................................................28
7.1.
Time and Events Table...............................................................................29
7.2.
Screening and Critical Baseline Assessments ............................................31
7.3.
Safety .........................................................................................................31
7.3.1.
Adverse Events (AE) and Serious Adverse Events (SAEs)..........31
7.3.1.1.
Time period and Frequency for collecting AE 
and SAE information...................................................31
 
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7.3.1.2.
Method of Detecting AEs and SAEs ...........................32
7.3.1.3.
Follow-up of AEs and SAEs........................................32
7.3.1.4.
Cardiovascular and Death Events ..............................32
7.3.1.5.
AEs of Special Interest ...............................................32
7.3.1.6.
Regulatory Reporting Requirements for SAEs............33
7.3.2.
Pregnancy ...................................................................................33
7.3.3.
Physical Exams ...........................................................................34
7.3.4.
Vital Signs....................................................................................34
7.3.5.
Electrocardiogram (ECG).............................................................34
7.3.6.
Clinical Safety Laboratory Assessments ......................................34
7.3.7.
Estimated Glomerular Filtration Rate (eGFR) ..............................37
7.3.8.
Diabetic Dietary, Exercise, and Home Plasma Glucose 
Monitoring Advice ........................................................................37
7.3.9.
Hypoglycemic Events...................................................................37
7.4.
Tracking of Albiglutide Liquid Auto-injector Failures and User Errors..........38
7.5.
Immunogenicity...........................................................................................38
7.6.
Efficacy.......................................................................................................39
7.7.
Value Evidence and Outcomes...................................................................39
7.8.
Genetics .....................................................................................................39
8.
DATA MANAGEMENT ...........................................................................................39
9.
STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................40
9.1.
Hypotheses.................................................................................................40
9.2.
Sample Size Considerations.......................................................................40
9.2.1.
Sample Size Assumptions ...........................................................40
9.2.2.
Sample Size Sensitivity................................................................40
9.2.3.
Sample Size Re-estimation or Adjustment...................................40
9.3.
Data Analysis Considerations .....................................................................40
9.3.1.
Analysis Populations....................................................................40
9.3.2.
Interim Analysis ...........................................................................40
9.4.
Key Elements of Analysis Plan ...................................................................41
9.4.1.
Primary Analyses.........................................................................41
9.4.2.
Exploratory Analyses ...................................................................41
9.4.3.
Other Analyses ............................................................................42
10. STUDY GOVERNANCE CONSIDERATIONS........................................................42
10.1.
Posting of Information on Publicly Available Clinical Trial Registers............42
10.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................42
10.3.
Quality Control (Study Monitoring) ..............................................................43
10.4.
Quality Assurance.......................................................................................43
10.5.
Study and Site Closure ...............................................................................43
10.6.
Records Retention......................................................................................44
10.7.
Provision of Study Results to Investigators, Posting of Information 
on Publically Available Clinical Trials Registers and Publication .................45
10.8.
Review Committees....................................................................................45
11. REFERENCES.......................................................................................................46
12. APPENDICES........................................................................................................47
12.1.
Appendix 1 – Abbreviations and Trademarks..............................................47
 
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12.2.
Appendix 2: GSK Modified List of Highly Effective Methods for 
Avoiding Pregnancy in Females of Reproductive Potential (FRP)...............49
12.3.
Appendix 3: Liver Safety Required Actions and Follow up 
Assessments ..............................................................................................50
12.4.
Appendix 4: Definition of and Procedures for Recording, Evaluating, 
Follow-Up and Reporting of Adverse Events...............................................53
12.4.1.
Definition of Adverse Events........................................................53
12.4.2.
Definition of Serious Adverse Events...........................................54
12.4.3.
Definition of Cardiovascular Events .............................................55
12.4.4.
Recording of AEs and SAEs ........................................................56
12.4.5.
Evaluating AEs and SAEs............................................................56
12.4.6.
Reporting of SAEs to GSK...........................................................58
12.5.
Appendix 5: Collection of Pregnancy Information........................................59
12.5.1.
Collection of Pregnancy Information ............................................59
12.5.2.
Appendix 6: Immunogenicity Testing Algorithm............................60
12.6.
Appendix 7: Genetic Research ...................................................................62
12.7.
Appendix 8: Patient Experience and Satisfaction Questionnaire.................65
12.8.
Appendix 9: Country Specific Requirements...............................................67
 
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1.
PROTOCOL SYNOPSIS FOR STUDY 204682
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. 
This open-label extension (Study 204682) to Study 200952 will provide additional safety, 
tolerability and immunogenicity data for the albiglutide liquid drug product.
Objective(s)/Endpoint(s)
Primary

To provide extended safety, tolerability 
and immunogenicity data for the 
albiglutide liquid drug product.

Adverse events (AEs) and serious adverse 
events (SAEs), physical examinations, 
clinical laboratory evaluations, vital signs, 
and 12-lead electrocardiograms (ECGs).

Anti-albiglutide antibody production over 
time.
Exploratory 

To provide safety and tolerability data on 
the transition from albiglutide lyophilized to 
liquid drug product.

To further evaluate the PD effect of 
albiglutide liquid drug product on HbA1c 
and FPG.  

AEs and SAEs, physical examinations, 
clinical laboratory evaluations, vital signs, 
and 12-lead ECGs.

Anti-albiglutide antibody production over 
time.

Change from baseline in HbA1c and FPG at 
Week 52.

To gain additional patient experience with 
the albiglutide liquid drug product via auto-
injector.

Exploring patient experience and 
satisfaction.
Overall Design

This is a 26 week, open-label, single group, multicenter, extension study to 
Study 200952. This extension study will provide extended safety, tolerability and 
immunogenicity data for the albiglutide liquid drug product.

This extension study will recruit subjects who have completed Study 200952 and 
satisfy all inclusion/exclusion criteria.
 
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
In addition to receiving albiglutide liquid drug product, subjects will continue on their 
current regimen of diet and exercise or stable dose of background metformin (if 
applicable).
Treatment Arms and Duration

This extension study will comprise 2 study periods: treatment (26 weeks) and post-
treatment follow-up (8 weeks). 

All subjects will receive 50 mg albiglutide liquid drug product via auto-injector.

Study treatment will be administered once weekly by s.c. injection in the abdomen, 
thigh, or upper arm.
Type and Number of Subjects

This extension study will recruit subjects who have completed Study 200952 and 
satisfy all inclusion/exclusion criteria.

A maximum of 300 subjects will be eligible to take part in this extension study. 
Analysis
Primary analyses:
The overall general safety and tolerability of albiglutide liquid drug product will be 
evaluated in tabular and/or graphical format and summarized descriptively. 
The evaluation of the safety and tolerability as assessed by immunogenicity of albiglutide 
liquid drug product will be provided by reporting descriptive statistics.
Exploratory analyses:
The overall general safety and tolerability of albiglutide liquid drug product for subjects 
who are randomized to albiglutide lyophilized drug product in Study 200952 and 
transition to albiglutide liquid drug product in this extension study will be evaluated in 
tabular and/or graphical format and summarized descriptively. 
The safety and tolerability as assessed by immunogenicity for the subject who transition 
to albiglutide liquid drug product in the extension study will be summarized 
descriptively.
HbA1c and FPG change from baseline will be summarized descriptively and/or 
graphically. 
Patient experience and satisfaction with the auto-injector and albiglutide liquid product as 
measured by a self completed patient exit questionnaire at the end of treatment visit 
(Week 52) will be assessed using summary statistics.
 
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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 
and has been approved by the US FDA, the EMA and other regulatory agencies. 
2.1.
Study Rationale
Study 200952, a randomized, double-blind, repeat-dose study in subjects with T2DM will 
determine if there are any clinically relevant differences between albiglutide liquid drug 
product and albiglutide lyophilized drug product with respect to safety, tolerability and 
pharmacodynamic (PD) response. This open-label extension (Study 204682) to Study 
200952 will provide additional safety, tolerability and immunogenicity data for the 
albiglutide liquid drug product.
3.
OBJECTIVE(S) AND ENDPOINT(S)
Objectives
Endpoints
Primary

To provide extended safety, tolerability 
and immunogenicity data for the 
albiglutide liquid drug product.

AEs and SAEs, physical examinations, 
clinical laboratory evaluations, vital signs, 
and 12-lead ECGs.

Anti-albiglutide antibody production over 
time.
Exploratory 

To provide safety and tolerability data on 
the transition from albiglutide lyophilized to 
liquid drug product.

To further evaluate the PD effect of 
albiglutide liquid drug product on HbA1c and
FPG.  

AEs and SAEs, physical examinations, 
clinical laboratory evaluations, vital signs, 
and 12-lead ECGs.

Anti-albiglutide antibody production over 
time.

Change from baseline in HbA1c and FPG at 
Week 52.

To gain additional patient experience with 
the albiglutide liquid drug product via auto-
injector.

Exploring patient experience and 
satisfaction.
4.
STUDY DESIGN
4.1.
Overall Design

This is a 26 week, open-label, single group, multicenter, extension study to 
Study 200952. This extension study will provide extended safety, tolerability and 
immunogenicity data for the albiglutide liquid drug product.
 
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
This extension study will recruit subjects who have completed Study 200952 and 
satisfy all inclusion/exclusion criteria (Section 5).

In addition to receiving albiglutide liquid drug product, subjects will continue on their 
current regimen of diet and exercise or stable dose of background metformin (if 
applicable).

An overview of the study design is provided in Figure 1
Figure 1
Study Schematic
Study Week
Albiglutide active lyophilized DCC pen injector + 
placebo liquid autoinjector (N= 150)
Albiglutide active liquid autoinjector + placebo 
lyophilized DCC pen injector   (N=150)
Study 200952
26-Week study
Study 200952
Primary Endpoint
52
26
Study 204682
26-Week Extension Study
Albiglutide active liquid autoinjector (N=300 
approximately)
36
42
48
Extension Study Visit
1
3
4
5
6
2
30
Follow-up
7
60
End of Treatment
4.2.
Treatment Arms and Duration

This extension study will comprise 2 study periods (Figure 1): treatment (26 weeks) 
and post-treatment follow-up (8 weeks). 

All subjects will receive 50 mg albiglutide liquid drug product via auto-injector.

Study treatment will be administered once weekly by s.c. injection in the abdomen, 
thigh, or upper arm.

The first dose of study treatment will be administered by the subject during the clinic 
visit (Visit 1, Week 26) with supervision from clinic staff. All further doses of study 
treatment will be self-administered by the subject.

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

This extension study will recruit subjects who have completed Study 200952 and 
satisfy all inclusion/exclusion criteria (Section 5).

Maximum of 300 subjects will be eligible to take part in this extension study. 
4.4.
Design Justification
This is an open-label, long term extension to Study 200952.  All subjects may choose to 
continue in the extension study if eligible to participate.  The selected 26 week extension 
 
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treatment duration should appropriately capture the continuation of the safety, tolerability 
and immunogenicity data for the albiglutide liquid drug product. 
4.5.
Dose Justification
Phase III studies confirmed the glycemic efficacy of both 30 mg and 50 mg doses of 
albiglutide lyophilized drug 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 Investigator Brochure [IB] for further details).
In this extension study all subjects will receive 50 mg of albiglutide liquid drug product 
once weekly for 26 weeks.
4.6.
Benefit:Risk Assessment
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.
The following sections outline the risk assessment and mitigation strategy for this 
protocol which would apply to the new liquid drug product in development.
A detailed description of the characteristics of the liquid drug product in the auto-injector 
device and results of nonclinical studies with this investigational formulation are 
presented in the IB Supplement. 
Summary characteristics of the liquid drug product are shown in Table 1.
Table 1
Composition of Albiglutide (Liquid for Injection, 30 mg and 50 mg)
Component
Liquid Albiglutide
30 mg dose
50 mg dose
Injector type
Pre-filled syringe with auto-injector  
Final formulation pH
5.9
Final albiglutide concentration
50 mg/mL
Injection volume
0.6 mL
1.0 mL
Stability data thus far suggest that the same product-related variants/impurity profiles are 
present in the liquid and commercial lyophilized drug products when stored at the 
 
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recommended conditions.  Based on the current understanding of albiglutide degradation 
pathways and clinical outcomes from exposure to variants/impurities, similar 
pharmacokinetic (PK), PD, and clinical comparability between the liquid drug product 
and the lyophilized drug product is expected. 
4.6.1.
Risk Assessment
Key identified and potential risks associated with administration of albiglutide 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 drug product and the 
investigational liquid drug product. No risks specific to the liquid drug product have been 
identified in non-clinical studies to date.  Mitigation strategies for this study have been 
incorporated for those risks (e.g., immunogenicity, injection site reactions) where a 
potential for differences between the liquid and lyophilized drug products has been 
recognized.
Please also refer to the IB and any 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 
were excluded from entering study 200952.
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 5.4).
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 were excluded from 
entering study 200952.
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  were excluded from 
entering study 200952
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. 
Subjects are neither allowed to use insulin nor insulin 
secretagogues during the study. Except as part of 
hyperglycemia rescue (see Section 5.3)
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 
Hypersensitivity reactions are of potential concern with any 
injected protein and were reported rarely in the Phase III 
Subjects with known allergy to any GLP-1 receptor agonist 
or excipients of albiglutide are excluded from entering
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
antidrug antibodies, severe hypersensitivity reactions, and 
other potential immune-related adverse events)
program with lyophilized albiglutide. 
Risk assessment of the albiglutide molecule predicted low 
immunogenic potential, which was substantiated for the 
commercial lyophilized 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 ISRs (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 drug product to 
form aggregates could have an impact on anti-drug 
antibody characteristics or immune related AE.  However, 
the likelihood of clinically important changes in anti-drug 
antibody characteristics or immune related AEs with the 
albiglutide liquid drug product compared to the lyophilized 
product is considered low based on the absence of 
substantive qualitative differences between formulations. 
study 200952
Subjects will be informed of the symptoms of severe 
hypersensitivity or allergy and be advised to seek medical 
assistance immediately. 
The development of anti-albiglutide antibodies and of 
injection site reactions 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 formulation, 
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 anti-drug 
antibody positive subjects reported one or more injection 
site reactions) than among those who were consistently 
antibody negative (14% of the antidrug antibody negative 
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.
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
subjects reported one or more injection site reactions).  
Overall, for lyophilized albiglutide, ISRs 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 drug 
product) may impact the injection site reaction profile.
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) were
excluded from entering study 200952.  
Risk communication via guidance for investigators (see 
Section 6 of the IB) and informed consent form for 
subjects.
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) were excluded from entering study 200952.
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 5.4).
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 
Subjects with a history of cancer were excluded from 
enetering. study 200952
Risk communication via guidance for investigators (see 
 
 
 
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Potential Risk of Clinical Significance
Summary of Data/Rationale for Risk
Mitigation Strategy
biological plausibility [European Public Assessment 
Report, 2014], and hematological malignancies [FDA
Summary Basis of Approval, 2014].
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+ 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 were excluded from entering 
study 200952 .
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 5.4.1).
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 
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 .
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
compared to those with mild renal impairment. GI events 
may lead to dehydration and worsen renal function. 
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 were excluded from Study 
200952.
 
 
 
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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 currently no data available for the use of the albiglutide liquid drug product in 
humans. 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 drug product and lyophilized drug product 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 that have been demonstrated in subjects with T2DM.
5.
SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings, precautions, contraindications, AEs, and other 
pertinent information on the GlaxoSmithKline (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 albiglutide 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 extension study only if all of the following 
criteria apply:
[1] TYPE OF SUBJECT 
1.
Subjects who have completed the 26 week Treatment Phase of Study 200952
 
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[2] SEX
2.
Male or female
3.
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 
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.
[3] INFORMED CONSENT
4.
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] TYPE OF SUBJECT
1.
Subject meets one or more of the withdrawal stopping criteria at Visit 1 (Week 26) 
(see Section 5.4)
 
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5.3.
Hyperglycemia Rescue
During the study of diabetics, there is always the possibility of hyperglycemia which 
might impact subject safety. 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
≥Week 26 and <Week 52
HbA1c ≥8.5% 
1.
HbA1c = glycosylated hemoglobin
Subjects can be rescued at any time. Subjects who qualify for rescue should return to the 
study center for a rescue visit, which includes efficacy assessments. The laboratory 
assessments should include safety laboratory tests (e.g., chemistry and complete blood 
count) and HbA1c. 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 and uptitration 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 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 study medication and appropriate 
rescue therapy initiated. Such subjects will continue to be followed in the study for their 
cardiovascular and other safety information; however, they will not receive further 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.
5.4.
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 5.4.1

QTc abnormalities exceeding the threshold criteria outlined in Section 5.4.2.

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 discontinue active participation in the study will no longer receive 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. 
5.4.1.
Liver Chemistry Stopping Criteria
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 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 3x upper limit of normal (ULN) 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.
5.4.1.1.
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.
5.4.2.
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 be withdrawn from the study:

QTcF > 500 msec (or 530 ms for subjects with bundle-branch block or 
pacemaker)
 
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5.5.
Subject and Study Completion
A completed subject is one who has completed the 26 week treatment phase of the 
extension 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.
Study Treatment
Product name:
Albiglutide liquid auto-injector
Dosage form/Delivery system:
Albiglutide liquid drug product is provided as a fixed-dose, 
disposable auto-injector containing albiglutide liquid drug 
product (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 drug product.
Albiglutide liquid drug product (50mg) has a pH of 5.9.
The auto-injector delivers the study treatment in an injection 
volume of 1.0 mL for the 50 mg dose.
Unit dose strength(s)
/Dosage level(s):
50mg albiglutide
Route of Administration
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 at any time of day without regard to meals
6.2.
Treatment Assignment
All subjects will receive 50 mg albiglutide liquid drug product via auto-injector.
 
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6.3.
Planned Dose Adjustments
Down-titration (dose reduction) of albiglutide from 50 mg to 30 mg is NOT permitted. If 
a subject experiences tolerability issues with the 50mg dose then the subject may be 
withdrawn from the study at the discretion of the investigator.
Subjects on a stable dose of metformin at the start of study 200952 may have their 
metformin dose adjusted during the extension study at the discretion of the investigator 
based on clinical need.
6.4.
Blinding
This extension study will be an open-label study.
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). 
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.
 
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6.7.
Compliance with Study Treatment Administration
The subject or designee will administer study treatment at the time points specified in the 
Time and Events Table (Section 7.1). 
Subjects will be instructed to return all unused and used auto-injectors at the visits 
specified in the Time and Events Table (Section 7.1) in order to perform drug 
accountability and determine compliance. In addition, subjects will be provided with a 
pre-printed card at each dispensing visit to record the date of each dose. The card is to be 
returned at the next dispensing visit.
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 four 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 52 visit, subjects will return to the study centre in 8 
weeks for the post-treatment follow-up visit (Week 60 visit) and will complete the study. 
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.
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 Visit 1 (Week 26) 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.
 
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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
drug product taken as study treatment) are prohibited.

Any investigational drug other than study treatment (albiglutide liquid drug 
product).

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.
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.
 
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7.1.
Time and Events Table
Procedure
Treatment
11End of 
Treatment
Follow-up12
Extension Study Visit
1
2
3
4
5
6
7
Study Week
2613
30
36
42
48
52
60
Informed consent for Study 204682
X
Inclusion/exclusion criteria review1
X
Full (F) or brief (B) physical exam2
F
B
B
B
B
F
F
Weight
X
X
X
X
X
X
X
12-lead ECG3
X
X
X
Vital signs
X
X
X
X
X
X
X
Serum (S)/Urine (U) pregnancy test (WCBP)
S
U
U
U
U
S
Clinical chemistry/hematology samples4
X
X
X
X
X
X
Lipids (including total cholesterol, LDL-C, HDL C, triglycerides, 
FFAs)4
X
X
X
Urinalysis5
X
X
HbA1c 6,7
X
X
X
X
X
X
X
FPG 7
X
X
X
X
X
X
X
eGFR
X
X
X
Immunogenicity sample8
X
X
X
X
X
Review AE/SAE, concomitant medication and hypoglycemia 
events 
X
X
X
X
X
X
X
Advice on diet and exercise9
X
X
X
X
X
X
Subject Experience / Satisfaction Exit Questionairre
X
Study treatment  dispensed 
X
X
X
X
X
Study treatment compliance10
X
X
X
X
X
WCBP: Women of child bearing potential; FFA: free fatty acids; LDL-c:  low density lipoproteins cholesterol; HDL-c: high density lipoproteins cholesterol
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 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 7.3.3.
3.
12-lead ECGs will be obtained before measurement of vital signs and collection of blood samples for laboratory testing. See Section 7.3.5.
4.
Clinical chemistry and hematology assessments are described in Section 7.3.6.
 
 
 
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5.
Urine samples should be collected in the early morning.
6.
Blood samples for HbA1c should be collected before administration of study treatment.
7.
Subjects will have their FPG and HbA1c levels evaluated to monitor for potential hyperglycemia.
8.
Blood samples for immunogenicity are to be collected before study drug administration.
9.
Standard diabetic dietary and exercise advice will be reinforced through the end-of-treatment visit. 
10. Compliance will be assessed as described in Section 6.7.
11. Subjects who discontinue study treatment should be handled as described in Section 5.4.
12. Follow-up visit for subjects who have discontinued study treatment (see Section 5.4) or subjects who have completed the 52 week treatment period.
13. Visit 1 of 204682 is also the end of treatment visit in Study 200952.
14. Visit 1 of Study 204682; albiglutide liquid drug product administered to all study subjects.
 
 
 
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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.
Full details of assessments undertaken at Visit 1 (Week 26) are provided in the Time and 
Events Table Section 7.1.
7.3.
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.
7.3.1.
Adverse Events (AE) and Serious Adverse Events (SAEs)
The definitions of an AE or SAE can be found in Appendix 4.
The investigator and their designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE. 
7.3.1.1.
Time period and Frequency for collecting AE and SAE information

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. 

AEs will be collected from the start of study treatment until the follow-up contact
(see Section 7.3.1.3), 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.

All SAEs will be recorded and reported to GSK within 24 hours, as indicated in 
Appendix 4.

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 4.
 
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7.3.1.2.
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?” 
7.3.1.3.
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 7.3.1.5) 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 5.4). Further information on follow-up procedures is 
given in Appendix 4.
7.3.1.4.
Cardiovascular and Death Events
For any cardiovascular events detailed in Appendix 4 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 
Medical Dictionary for Regulatory Activities (MedDRA) terms. The CV information 
should be recorded in the specific cardiovascular section of the CRF within one week of 
receipt of a CV Event data query prompting its completion. 
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.
7.3.1.5.
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 7.3.1.4)
 
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
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 be withdrawn from the study and should not be 
rechallenged with albiglutide (see Section 5.4 for complete list of AEs of special interest
requiring withdrawal).
7.3.1.6.
Regulatory Reporting Requirements for SAEs
Prompt notification by the investigator to GSK of SAEs 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. 
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.
7.3.2.
Pregnancy

If a subject becomes pregnant during the study they should discontinue 
Investigational Product.
 
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
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 5.
7.3.3.
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
Weight will be measured at each clinic visit.
7.3.4.
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.
7.3.5.
Electrocardiogram (ECG)
A single 12-lead ECG recording (with subject in semi-recumbent 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 
5.4.2 for QTc withdrawal criteria.
All ECGs will be performed before measurement of vital signs and collection of blood 
samples for laboratory testing.
7.3.6.
Clinical Safety Laboratory Assessments
All protocol required laboratory assessments, as defined in Table 4 must be conducted in 
accordance with the Laboratory Manual, and Protocol Time and Events Schedule in 
 
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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.
All study-required laboratory assessments will be performed by a central laboratory. The 
results of the test must be entered into the eCRF.
Hematology, clinical chemistry, urinalysis and additional parameters to be tested are 
listed in Table 4.
 
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Table 4
Protocol Required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Platelet Count
RBC Indices:
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

Lipids including total cholesterol, LDL-C, HDL C, triglycerides, 
FFAs (fasting) 2

FSH and estradiol (as needed in women of non-child bearing 
potential only)

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 5.4.1 and Appendix 3.
2.
Fasting is defined as no food or drink (except water) for at least 8 hours before blood draw
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.
 
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7.3.7.
Estimated Glomerular Filtration Rate (eGFR)
Serum creatinine will be measured at the timepoints 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).
7.3.8.
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 1 (Week 26) and reinforced at each study site visit through the 
End of treatment visit (Week 52). 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.
7.3.9.
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 4) 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.
7.4.
Tracking of Albiglutide Liquid Auto-injector Failures and 
User Errors
All albiglutide liquid auto-injector failures and user errors must be detected, documented, 
and reported by the investigator throughout the study. Detailed information on auto-
injector failures and user errors will be collected on the Auto-injector Failure Reporting 
Form.
NOTE: Albiglutide 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 7.3.1.
7.5.
Immunogenicity
Serum for antidrug antibody testing will be obtained from all subjects before 
administration of study treatment according to the Time and Events Table in Section 7.1. 
With exception of Week 30, all other time points (Week 26, Week 36, Week 52 and 
Week 60 (Follow-up)) are comparable to those collected in the Phase III Harmony 
studies with lyophilized albiglutide and may serve as comparators to the formulation of 
the marketed product.
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 6).
 
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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 as per the Protocol Time and Events 
Schedule in Section 7.1.
7.6.
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.
7.7.
Value Evidence and Outcomes
In this open-label extension study, subjects will self-administer their medication via the 
auto-injector device, thereby gaining first time personal experience with its use.  Subject 
experience with the auto-injector device and treatment will be collected via a patient self-
completed exit questionnaire at the end of treatment visit (Week 52).  The close-ended 
questionnaire focuses on elements of burden, experience and satisfaction with the auto-
injector and albiglutide liquid drug product.  Specifically, the questions evaluate how 
comfortable subjects feel about using the device, how long it took for them to feel 
comfortable using the device, how easy they think it is to use, how long it takes to 
prepare/administer and whether they prefer it to other methods for self-injection 
(assuming that they have prior experience) (see Appendix 8 for further details) 
7.8.
Genetics
Information regarding genetic research is included in Appendix 7
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.
 
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9.
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
9.1.
Hypotheses
This open label study is designed to evaluate the extended safety and tolerability as 
assessed by immunogenicity of albiglutide liquid drug product when used in subjects 
with T2DM for additional 26 weeks.  The overall general safety and tolerability of 
albiglutide liquid drug product will be assessed by reporting descriptive statistics.
9.2.
Sample Size Considerations
The total number of subjects for this study will be determined by the number of subjects 
who give consents to enroll in this study from the parent Study 200952, have completed 
Study 200952, and satisfy all inclusion/exclusion criteria.  Therefore, it is anticipated to 
enroll a maximum of 300 eligible subjects who will receive albiglutide liquid drug
product.
9.2.1.
Sample Size Assumptions
No sample size assumptions are planned for this study.
9.2.2.
Sample Size Sensitivity
No sample size sensitivity is planned for this study.
9.2.3.
Sample Size Re-estimation or Adjustment
No sample size re-estimation is planned for this study.
9.3.
Data Analysis Considerations
9.3.1.
Analysis Populations
Safety Population:  The Safety Population is defined as all enrolled subjects who receive 
at least 1 dose of study medication. 
Intent-to-Treat (ITT) Population: The ITT Population will include all subjects who 
receive at least 1 dose of the study medication and have a baseline assessment. 
Other analysis populations may be defined in the reporting and analysis plan (RAP).
9.3.2.
Interim Analysis
No interim analysis is planned for this study.
 
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9.4.
Key Elements of Analysis Plan
9.4.1.
Primary Analyses
The overall general safety and tolerability of albiglutide liquid 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. 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 7.3.9.
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).
The evaluation of the safety and tolerability as assessed by immunogenicity of albiglutide 
liquid drug product will be provided by reporting descriptive statistics.
Anti-albiglutide antibody results will be summarized. In addition, the number and 
percentage of subjects with positive results along with the antibody titer values will be 
provided by visit.
Summary data for the primary analyses will be presented by visit and by subjects who 
needed hyperglycemic rescue during Study 200952 (at visit 1 of the current study), by 
subjects who did not need hyperglycaemic rescue during study 200952, and overall.
9.4.2.
Exploratory Analyses
The overall general safety and tolerability of albiglutide liquid drug product as assessed 
by AEs and SAEs, physical examinations, clinical laboratory evaluations, vital sign 
measurements, and 12-lead ECGs for subjects who are randomized to albiglutide 
lyophilized in Study 200952 and transition to albiglutide liquid drug product in this 
extension study will be summarized analogous to the data in Section 9.4.1.
The safety and tolerability as assessed by immunogenicity for the subjects who transition 
to albiglutide liquid drug product in this extension study will be summarized 
descriptively.  
 
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The exploratory endpoints change from baseline for HbA1c and FPG at week 52 for those 
subjects who transition to albiglutide liquid product will be presented in tabular and/or 
graphical format and summarized descriptively together with the 95% CI.
Patient experience and satisfaction will be assessed using descriptive summary statistics
of individual questions of the 9-item questionnaire (Appendix 8). 
Summary data for the exploratory analyses will be presented by subjects who needed 
hyperglycemic rescue during Study 200952 (at Visit 1 of the current study), by subjects 
who did not need hyperglycaemic rescue during study 200952, and overall.
9.4.3.
Other Analyses
No other analyses will be conducted for this study.
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 favourable opinion/approval from the 
appropriate regulatory agency to conduct the study in accordance with International 
Conference on Harmonization (ICH) 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
 
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
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.
10.3.
Quality Control (Study Monitoring)

In accordance with applicable regulations including 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 
 
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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 
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.  
 
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
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.
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.
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
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
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.
 
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12.
APPENDICES
12.1.
Appendix 1 – Abbreviations and Trademarks
Abbreviations
AE
adverse event
ALT (SGPT)
alanine aminotransferase (serum glutamic pyruvic 
transaminase)
AST (SGOT)
aspartate aminotransferase (serum glutamic oxaloacetic 
transaminase)
BUN
blood urea nitrogen
CI
confidence interval
CPK
creatine phosphokinase
CV
cardiovascular
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
GGT
gamma glutamyl transferase
GI
gastrointestinal
GLP-1
glucagon-like peptide-1
GSK
GlaxoSmithKline
HA
human albumin
HbA1c
glycated hemoglobin
hCG
human chorionic gonadotrophin
HDL-c
high density lipoproteins
HRT
hormone replacement therapy
IB
Investigator’s Brochure
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
INR
international normal range
IP
Investigational product
IRB
Institutional Review Board
ISRs
injection site reactions
ITT
intent-to-treat
LDH
lactate dehydrogenase
LDL-c
low density lipoproteins; 
 
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MACE
major adverse cardiovascular event
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
MSDS
Material Safety Data Sheet
MTC
medullary thyroid cancer
PAC
Pancreatitis Adjudication Committee
PD
pharmacodynamics
PK
pharmacokinetics
OC RDC
Oracle Clinical Remote Data Capture
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
ULN
upper limit of normal range
WBC
white blood cell
WCBP
women of child bearing potential
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
MedDRA
SpectrMAX
 
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12.2.
Appendix 2: GSK Modified List of Highly Effective Methods 
for Avoiding Pregnancy in Females of Reproductive 
Potential (FRP)
1.
Contraceptive subdermal implant that meets effectiveness criteria including a <1% 
rate of failure per year, as stated in the product label.
2.
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]
3.
Oral Contraceptive, either combined or progestogen alone [Trussell, 2011] 
4.
Injectable progestogen [Trussell, 2011]
5.
Contraceptive vaginal ring [Trussell, 2011]
6.
Percutaneous contraceptive patches [Trussell, 2011]
7.
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.
8.
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) 
International 
Normal
Range (INR)2
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)

Do not restart/rechallenge subject with 

Viral hepatitis serology4

Only in those with underlying chronic 
hepatitis B at study entry (identified by 
positive hepatitis B surface antigen)
quantitative hepatitis B deoxyribonucleic 
acid (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).

Fractionate bilirubin, if total 
 
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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
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 adduct 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 
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 
 
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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.
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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