Study 110933: Albiglutide Versus Placebo in Insulin-treated Subjects With New-onset Type 1 Diabetes Mellitus
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Sponsor: GlaxoSmithKline

2011N125236_02
CONFIDENTIAL
The GlaxoSmithKline group of companies
GLP110933
1
TITLE PAGE
Division: Worldwide Development
Information Type: Protocol Amendment
Title:
Study 110933: Albiglutide versus Placebo in insulin-treated 
Subjects with new-onset type 1 diabetes mellitus
Compound Number:
GSK716155
Development Phase:
II
Effective Date:
24-SEP-2014
Protocol Amendment Number:  02
Author (s):
 
Revision Chronology
GlaxoSmithKline
Document Number
Date
Version
2011N125236_00
2014-MAY-29
Original
2011N125236_01
2014-SEP-12
Amendment No. 1
Clarification added to wording in the treatment compliance section regarding Week 2. 
Clarification added regarding the collection of daily insulin use prior to Baseline. 
Correction of typographical errors 
2011N125236_02
2014-SEP-24
Amendment No. 2
Change to the acceptable contraceptive methods for UK sites only at the request of the 
MHRA. 
Copyright 2014 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD

PPD

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SPONSOR INFORMATION PAGE
Clinical Study Identifier: GLP110933
Sponsor Legal Registered Address:
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Sponsor Contact Address
GlaxoSmithKline Research & Development Limited
Iron Bridge Road 
Stockley Park West, Uxbridge, Middlesex, UB11 1BU, UK
Telephone:  
 
In some countries, the clinical trial sponsor may be the local GlaxoSmithKline affiliate 
company (or designee). Where applicable, the details of the Sponsor and contact person 
will be provided to the relevant regulatory authority as part of the clinical trial 
submission.
Sponsor Medical Monitor Contact Information: 
Dr 
 MBChB (Hons) MRCP PhD MFPM
Metabolic Pathways and Cardiovascular Unit
GlaxoSmithKline Research & Development Limited
Iron Bridge Road 
Stockley Park West, Uxbridge, Middlesex, UB11 1BU, UK
Telephone: 
Mobile: 
Sponsor Serious Adverse Events (SAE)* Contact Information:
*SAEs to be submitted via the eCRF.  
Please see Study Procedures Manual for details regarding submission of back-up paper 
SAE CRF pages.
Regulatory Agency Identifying Number(s): Eudra CT: 2014-001825-33
PPD
PPD
PPD
PPD

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INVESTIGATOR PROTOCOL AGREEMENT PAGE
For protocol number GLP110933
I confirm agreement to conduct the study in compliance with the protocol, as amended by 
this protocol amendment.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure that site 
staff receives the appropriate information throughout the study. 
Investigator Name:
Investigator Address:
Investigator Phone Number:
Investigator Signature
Date

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TABLE OF CONTENTS
PAGE
LIST OF ABBREVIATIONS.............................................................................................9
PROTOCOL SUMMARY...............................................................................................11
1.
INTRODUCTION....................................................................................................16
1.1.
Background ................................................................................................16
1.2.
Rationale ....................................................................................................17
1.3.
Benefit:Risk Assessment ............................................................................19
1.3.1.
Risk Assessment .........................................................................19
1.3.2.
Benefit Assessment.....................................................................23
1.3.3.
Overall Benefit:Risk Conclusion...................................................24
2.
OBJECTIVE(S) ......................................................................................................24
2.1.
Primary Objective .......................................................................................24
2.2.
Secondary Objectives.................................................................................24
2.3.
Exploratory Objectives................................................................................25
3.
INVESTIGATIONAL PLAN.....................................................................................25
3.1.
Study Design ..............................................................................................25
3.2.
Discussion of Design ..................................................................................28
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA.......................................30
4.1.
Number of Subjects ....................................................................................30
4.2.
Inclusion Criteria.........................................................................................30
4.3.
Exclusion Criteria........................................................................................31
4.4.
Withdrawal Criteria .....................................................................................33
4.5.
Screening/Run-in Failures ..........................................................................35
5.
STUDY TREATMENTS..........................................................................................35
5.1.
Investigational Product and Other Study Treatment....................................35
5.1.1.
Investigational Product Administration During the 
Treatment Period.........................................................................36
5.1.2.
Insulin Titration ............................................................................37
5.1.2.1.
Basal Insulin Titration .................................................38
5.1.2.2.
Meal-time Insulin Titration...........................................38
5.1.3.
Surveillance of Insulin Titration ....................................................39
5.2.
Treatment Assignment................................................................................40
5.3.
Blinding.......................................................................................................40
5.4.
Product Accountability ................................................................................41
5.5.
Treatment Compliance................................................................................41
5.6.
Concomitant Medications and Non-Drug Therapies....................................41
5.6.1.
Permitted Medications and Non-Drug Therapies..........................41
5.6.2.
Prohibited Medications and Non-Drug Therapies.........................42
5.7.
Treatment after the End of the Study ..........................................................42
5.8.
Treatment of Study Treatment Overdose....................................................43
6.
STUDY ASSESSMENTS AND PROCEDURES .....................................................43
6.1.
Critical Baseline Assessments....................................................................48
6.2.
Standard of Diabetic Care...........................................................................48
6.3.
Efficacy.......................................................................................................48

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6.3.1.
Study Endpoints...........................................................................48
6.3.1.1.
Primary Endpoint........................................................48
6.3.1.2.
Secondary Endpoints .................................................48
6.3.1.3.
Exploratory Endpoints ................................................49
6.3.2.
Efficacy Assessments..................................................................50
6.3.2.1.
Mixed Meal Tolerance Test ........................................50
6.3.2.2.
Self Monitoring of Plasma Glucose.............................51
6.3.2.3.
7-Point Self-Monitored Plasma Glucose Profile ..........51
6.3.2.4.
72-hour Continuous Glucose Monitoring.....................52
6.3.2.5.
Daily Insulin Use.........................................................52
6.3.2.6.
HbA1c ........................................................................52
6.3.2.7.
Body Weight...............................................................52
6.3.2.8.
Audit of Diabetes Dependent Quality of Life 
(ADDQoL) ..................................................................53
6.4.
Safety .........................................................................................................53
6.4.1.
Safety Endpoints..........................................................................53
6.4.2.
Subject-Reported Hypoglycaemia Events....................................54
6.4.3.
Physical Examination...................................................................55
6.4.4.
Height and BMI............................................................................56
6.4.5.
Vital Signs....................................................................................56
6.4.6.
Electrocardiograms......................................................................56
6.4.7.
Clinical Laboratory Assessments .................................................56
6.4.7.1.
Estimated Glomerular Filtration Rate..........................58
6.4.8.
Immunogenicity Sampling (Anti-albiglutide Antibodies)................58
6.4.9.
Liver chemistry stopping and follow up criteria.............................58
6.4.10.
Adverse Events............................................................................61
6.4.10.1.
Definition of an AE......................................................61
6.4.10.2.
Definition of an SAE ...................................................62
6.4.10.3.
Sentinel Events ..........................................................63
6.4.11.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs.........................................................64
6.4.12.
Cardiovascular Events.................................................................64
6.4.13.
Death Events...............................................................................64
6.4.14.
Injection Site Reactions and Potential Systemic Allergic 
Reactions (e.g., rashes, urticaria, angioedema or 
anaphylaxis) ................................................................................64
6.4.15.
Pancreatitis..................................................................................65
6.4.16.
Pancreatic Cancer .......................................................................65
6.4.17.
Medullary Thyroid Cancer............................................................66
6.4.18.
Pneumonia ..................................................................................66
6.4.19.
Atrial Fibrillation/Atrial Flutter .......................................................66
6.4.20.
Pregnancy ...................................................................................66
6.4.21.
Time Period and Frequency of Detecting AEs and SAEs.............67
6.4.22.
Method of Detecting AEs and SAEs.............................................67
6.4.23.
Prompt Reporting of Serious Adverse Events and Other 
Events to GSK.............................................................................67
6.4.23.1.
Regulatory Reporting Requirements for SAEs............70
6.5.
Pharmacokinetics .......................................................................................70
6.6.
Pharmacogenetic Research........................................................................71
6.7.
Biomarker Samples ....................................................................................71
7.
DATA MANAGEMENT ...........................................................................................71

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8.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS...................................72
8.1.
Hypotheses.................................................................................................72
8.2.
Study Design Considerations......................................................................72
8.2.1.
Sample Size Assumptions ...........................................................72
8.2.2.
Sample Size Sensitivity................................................................73
8.2.3.
Sample Size Re-estimation..........................................................73
8.3.
Data Analysis Considerations .....................................................................74
8.3.1.
Analysis Populations....................................................................74
8.3.2.
Analysis Data Sets.......................................................................74
8.3.3.
Treatment Comparisons ..............................................................74
8.3.3.1.
Primary Comparisons of Interest ................................74
8.3.3.2.
Other Comparisons of Interest....................................74
8.3.4.
Interim Analysis ...........................................................................74
8.3.5.
Key Elements of Analysis Plan ....................................................74
8.3.5.1.
General Statistical Methods........................................74
8.3.5.2.
Subject Disposition and Demographic and 
Baseline Characteristics .............................................75
8.3.5.3.
Efficacy Analyses .......................................................75
8.3.5.3.1.
Primary Efficacy Analysis .......................75
8.3.5.3.2.
Secondary Efficacy Analyses..................77
8.3.5.3.3.
Exploratory Analyses..............................78
8.3.5.4.
Safety Analyses..........................................................79
8.3.5.5.
Immunogenicity analyses ...........................................79
8.3.5.6.
Pharmacokinetic Analyses..........................................79
8.3.5.7.
Pharmacokinetic/Pharmacodynamic Analyses ...........80
8.3.5.8.
Pharmacogenetic Analyses ........................................80
8.3.5.9.
Missing Data...............................................................80
8.3.5.10.
Laboratory Values Below Limits of 
Quantification and Repeat Testing..............................81
9.
STUDY CONDUCT CONSIDERATIONS ...............................................................81
9.1.
Posting of Information on Publicly Available Clinical Trial Registers............81
9.2.
Regulatory and Ethical Considerations, Including the Informed 
Consent Process ........................................................................................81
9.3.
Quality Control (Study Monitoring) ..............................................................82
9.4.
Quality Assurance.......................................................................................82
9.5.
Study and Site Closure ...............................................................................82
9.6.
Records Retention......................................................................................83
9.7.
Provision of Study Results to Investigators, Posting of Information 
on Publicly Available Clinical Trials Registers and Publication....................84
9.8.
Pancreatitis Adjudication Committee...........................................................84
10. REFERENCES.......................................................................................................85
11. APPENDICES........................................................................................................90
11.1.
Appendix 1: Pharmacogenetic Research ....................................................90
11.2.
Appendix 2: Liver Chemistry Stopping and Follow-up Criteria.....................95
11.3.
Appendix 3: Immunogenicity Testing ..........................................................96
11.4.
Appendix 4: Audit of Diabetes Dependent Quality of Life (AddQoL)............98
11.5.
Appendix 5: Country Specific Requirements.............................................104
11.6.
Appendix 6: Protocol Amendment Changes..............................................105
11.6.1.
Changes Resulting from Protocol Amendment 01......................105

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11.6.2.
Changes Resulting from Protocol Amendment 02......................109

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LIST OF ABBREVIATIONS
ADA
ADDQoL
AE
ALP
ALT
Anti-IA-2
Anti-GAD
AST
AUC
BLQ
-hCG
BMI
CGM
CHMP
CPK
CV
DCCT
DKA
DM
DNA
DPP-4
ECG
eCRF
eGFR
EMA
FDA
American Diabetes Association
Audit of Diabetes Dependent Quality of Life 
Adverse Event
Alkaline phosphatase
Alanine aminotransferase
Antibody to protein tyrosine phosphatase-like protein
Antibody to Glutamic Acid Decarboxylase
Aspartate aminotransferase
Area Under the Curve
Below level of quantification
-human chorionic gonadotropin
Body mass index
Continuous glucose monitoring
Committee for Medicinal Products for Human Use
Creatine phosphokinase
Cardiovascular
Diabetes Control and Complications Trial
Diabetic keoacidosis
Diabetes mellitus
Deoxyribonucleic acid 
Dipeptidypeptidase-IV
Electrocardiogram
electronic case report form
estimated Glomerular Filtration Rate
European Medicines Agency
Food and Drug Administration
FPG
Fasting plasma glucose
GCP
GCSP
Good Clinical Practice
Global Clinical Safety and Pharmacovigilance
GLP-1
Glucagon-like peptide-1
GLP-1R
Glucagon-like peptide-1 receptor
GSK
GlaxoSmithKline
HA
Human albumin
HbA1c
Glycosylated haemoglobin A1c
HPLC
High performance liquid chromatography
IAA
Insulin autoantibody
IB
Investigator’s Brochure
ICH
International Conference on Harmonisation
IDAA1c
Insulin Dose Adjusted A1c
IEC
Independent Ethics Committee
IgE
Immunoglobulin E
IgG
Immunoglobulin G
INR
International Normalised Ratio
IRB
Institutional Review Board 
ITT
Intent to treat
LDH
Lactate dehydrogenase

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IP
Investigational Product
IVRS
Interactive voice response system
LSLV
Last subject last visit
MAR
missing at random
MDRD
Modification of Diet in Renal Disease
MMTT
Mixed meal tolerance test
NAb
Neutralising antibody
NOT1DM
New-onset type 1 diabetes mellitus
PAC
Pancreatitis Adjudication Committee
PBMC
Peripheral blood mononuclear cell
PCR
Polymerase chain reaction
PD
Pharmacodynamic
PGx
Pharmacogenetic
PK
Pharmacokinetic
QoL
Quality of Life
QTc
RBCF
RAP
RNA
SAE
sc
SD
SMPG
SPM
SU
T1DM
T2DM
TZD
ULN
corrected QT interval
Residual beta-cell function
Reporting and analysis plan
Ribonucleic acid
Serious Adverse Event
Subcutaneous
Standard deviation
Self-monitored plasma glucose
Study Procedures Manual
Sulphonylurea
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Thiazolidinedione
Upper limit of normal
Trademark Information
Trademarks of the GlaxoSmithKline 
group of companies
Trademarks not owned by the 
GlaxoSmithKline group of companies
NONE
Ketostix
SAS

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PROTOCOL SUMMARY
Rationale
Despite introduction of modern analogue insulins, and improved methods of delivery 
such as continuous subcutaneous insulin infusion using a pump, glucose control in 
patients with type 1 diabetes mellitus (T1DM) remains suboptimal, leading to an 
increased burden of complications of diabetes including blindness, renal failure and 
amputation. It is recognised that patients with preserved pancreatic β-cell function and 
hence endogenous insulin production, who require a lower overall dose of insulin 
replacement therapy, achieve better glycaemic control and experience a reduced burden 
of long term complications. 
Glucagon-like peptide-1 receptor (GLP-1R) agonists stimulate insulin secretion in a 
glucose-dependent manner and suppress glucagon secretion, resulting in lower fasting 
plasma glucose and reduced postprandial glucose excursions with a low risk of 
hypoglycaemia. GLP-1R agonists also delay gastric emptying, increase satiety and are 
associated with modest weight reduction. These physiological effects of GLP-1 therapies 
may lead to an improvement in glycaemic control in subjects with T1DM.
Pre-clinical evidence from rodent models suggests that GLP-1R agonists may also 
preserve -cell function. This study seeks to evaluate the effect of albiglutide, a GLP-1R 
agonist, on endogenous insulin production, (measured by stimulated C-peptide), 
exogenous insulin requirements, (as measured by total daily insulin dose per kg of body 
weight, and glycaemic variability over one year in subjects with T1DM and residual -
cell function.  The results of this study will determine the next steps in the development 
of albiglutide as a novel therapy for subjects with T1DM.
Objectives and Endpoints
Objective
Endpoint
Primary
Determine the effect of albiglutide therapy 
versus placebo on endogenous insulin secretion 
over 52 weeks when added to standard of care 
in subjects with new onset type 1 diabetes 
mellitus (NOT1DM)
Primary Endpoint: Mean change from baseline 
in stimulated (from mixed meal tolerance test 
[MMTT]) 2 hour plasma C-peptide area under 
the curve (AUC) at Week 52
Secondary Endpoints linked to primary 
objective:
Mean change from baseline in stimulated (from 
MMTT) 2 hour plasma C-peptide AUC at Week 
16, 28 and Week 64
Maximum stimulated plasma C-peptide: the 
highest value at any time point during the 2 
hour MMTT after the subject has ingested the 
mixed meal at Baseline, Week 16, Week 28, 
Week 52 and Week 64

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Objective
Endpoint
Secondary
To assess the effect of albiglutide versus 
placebo on plasma glucagon concentration 
during a MMTT
Mean change from baseline in plasma 
glucagon AUC (from MMTT) at Week 16, 28, 
52 and Week 64
Determine the percentage of subjects meeting 
the definition of a responder (defined as having 
HbA1c ≤ 7.0% and mean daily insulin use < 0.5 
units/kg/day) and the percentage of subjects 
achieving partial remission status (i.e., defined 
as subjects with Insulin Dose Adjusted A1c 
(IDAA1C) 9.0) 
Percent of responders (defined as subjects with 
HbA1c < 7.0% and insulin dose < 0.5 
units/kg/day) at Weeks 4, 8, 16, 28, 40, 52 and 
64
Percent of subjects achieving insulin dose-
adjusted haemoglobin A1c (IDAA1C) 9.0 at 
Weeks 4, 8, 16, 28, 40, 52 and 64
To assess glycaemic control in both treatment 
groups as measured by HbA1c
Change from Baseline in HbA1c at Week 52 
and HbA1c over time (i.e., at Weeks 4, 8, 16, 
28, 40, 52 and 64
Determine differences in total daily insulin dose 
between treatment groups
Change from baseline in mean daily insulin use 
over the 3 days preceding the visit at Weeks 4, 
8, 16, 28, 40, 52 and 64. The mean daily insulin 
use value will be calculated, in units/kg/day, as 
the mean of the values of the total amount of 
insulin used per day on each of the 3 
consecutive days
Determine any differences in significant 
hypoglycaemia (i.e., events with plasma glucose  
< 3.9 mmol/L and/or requiring third party 
intervention) between treatment groups
Number of events of hypoglycaemia with 
confirmed self plasma glucose monitoring < 3.9 
mmol/L and/or requiring third party intervention 
(i.e., severe, documented symptomatic and 
asymptomatic hypoglycaemic events – see 
Section 6.4.2) occurring > Week 24 and 
Week 52
Compare glycaemic variability between 
treatment groups, as measured by 72-hour 
continuous glucose monitoring (CGM) and 7 
point glucose profile
Time spent with a plasma glucose <3.9 
mmol/L, between 3.9 and 10.0 mmol/L, and 
>10.0 mmol/L, respectively as performed by 
72-hour CGM at Baseline, Week 28 and Week 
52
Number and magnitude of hypoglycaemic (<3.9 
mmol/L) and hyperglycaemic excursions (> 
10.0 mmol/L) from the 7 point glucose profile at 
Baseline, Week 28 and Week 52
Determine the effect of albiglutide on body 
weight
Change from Baseline in body weight (kg) at 
Week 52 and Weight over time (i.e., at Weeks 
2, 4, 6, 8, 16, 28, 40, 52 and 64)
Assess the safety and tolerability of albiglutide in 
subjects with NOT1DM
Incidence of hypoglycaemia (in total and by 
each category as defined by ADA criteria (see 
Section 6.4.2) overall and in 3 monthly intervals 
(i.e., from Baseline to Week 12, >Week 12 to 

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Objective
Endpoint
Week 24, >Week 24 to Week 36, >Week 36 
to Week 52, >Week 52 to Week 64
Incidence of hypoglycaemia with plasma
glucose <3.1 mmol/L (< 56mg/dL) regardless of 
symptoms)
Incidence of daytime hypoglycaemia (in total 
and by ADA category) (defined as 
hypoglycaemic episodes with an onset 
between 06:00 h and 00:00 h (inclusive) and 
nocturnal hypoglycaemia (in total and by 
category) defined as hypoglycaemic episodes 
with an onset between 00:01 h and 05:59 h 
(inclusive) will be determined
Adverse events and serious adverse events
Other adverse events of special interest (AESI) 
(for example, cardiovascular, gastrointestinal, 
pancreatitis, malignancies (including pancreatic 
cancer and thyroid cancer), injection site 
reaction, liver events, potential systemic 
allergic reactions, atrial fibrillation/flutter, 
pneumonia, diabetic ketoacidosis [DKA i.e., 
ketonuria/ketonaemia, hyperglycaemia and 
acidaemia])
Assessment of clinical laboratory tests
(haematology, biochemistry, urinalysis)
Assessment of vital signs measurements, 12-
lead electrocardiograms (ECGs) and physical 
examinations
Immunogenicity (i.e., percentage of subjects 
developing anti-albiglutide antibodies and 
characterisation of anti-albiglutide antibodies)
To evaluate the albiglutide PK profile in subjects 
with NOT1DM 
Population estimates of PK parameters (e.g., 
apparent clearance [CL/F], apparent volume of 
distribution [V/F], first-order absorption rate 
constant [Ka]), associated inter-subject 
variability and residual error 
Covariates and covariate effects on subject PK
Population estimates of PD parameters (e.g., 
Emax, EC50), associated inter-subject variability 

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Objective
Endpoint
and residual error if permitted by the data
Exploratory
Assess the effect of albiglutide on T1DM-
associated auto-antibodies (antibody to glutamic 
acid decarboxylase (anti-GAD) antibody to 
protein tyrosine phosphatase-like protein (anti-
IA-2) and insulin autoantibody (IAA))
Change from baseline in anti-GAD, anti-IA-2 
and IAA antibody titres at Week 4, Week 16, 
Week 28, Week 40, Week 52 and Week 64
Explore whether urinary C-peptide could be used 
in future phase III studies as an alternative to 
plasma C-pepide AUC from mixed meal testing 
as a measure of endogenous insulin secretion
Correlation of urinary C-peptide 120 minute 
after a mixed meal (urinary creatinine 
corrected) with MMTT plasma C-peptide AUC 
assessed at Baseline, Week 16, Week 28, 
week 52 and Week 64
Evaluate the PK and PD (PK/PD) relationship 
between plasma albiglutide concentration and 
measures of glycaemic control (e.g., C-peptide, 
insulin use, HbA1c, etc) and other potential 
efficacy, tolerability (e.g., nausea and vomiting) 
and safety endpoints as data permit
Graphical or model-based exploration of PK/PD 
relationships between albiglutide exposure 
(e.g., steady state AUC) and selected PD 
endpoints if appropriate and permitted by the 
data
Assess the effect of albiglutide on biomarkers 
associated with autoimmune pathology over 52 
weeks in subjects with NOT1DM
A decision on whether to analyse biomarker 
samples will be made after review of efficacy 
endpoints at the end of the study. Exploratory 
biomarkers may include CD8-positive antigen-
specific T-cells and biomarkers for -cell death.
Assess the effect of albiglutide on diabetes-
related quality of life as measured by the Audit of 
Diabetes Dependent Quality of Life 
Questionnaire (ADDQoL).
Change from baseline in ADDQoL global and 
domain scores and overview item scores at 
Week 52.
Assess the effect of albiglutide on -cell function 
in the context of the prevailing glucose response 
to the MMTT
-cell function, expressed as an insulin 
secretion parameter, will be estimated by 
modelling glucose and c-peptide 
concentrations. The modelling process will 
include, but is not limited to, the deconvolution 
of C-peptide data in the context of the 
prevailing glucose response to the meal
Study Design
This is a Phase II, randomised, double-blind, parallel group, placebo controlled, 
multicentre study of 52 weeks treatment duration in subjects with NOT1DM. 
Approximately 68 eligible subjects will be randomised in a 3:1 ratio such that: 

51 subjects receive albiglutide 30 mg once weekly (with increase to 50 mg once 
weekly at Week 6 if the 30 mg dose is tolerated) added-on to insulin therapy

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
17 subjects receive placebo once weekly added-on to insulin therapy 
Blinded reduction of randomised study medication to the 30 mg once weekly dose may 
occur in the event of GI intolerability (i.e., nausea, vomiting or diarrhoea) after 
discussion between the investigator and medical monitor.
During the study, subjects will perform self monitored plasma glucose monitoring at least 
4 times daily and adjust their basal and meal-time insulin requirements according to 
protocol-defined algorithm/guidance.  
The total duration of a subject’s participation will be approximately 72 weeks (up to 8 
weeks of Screening, 52 weeks of treatment and 12 weeks of Post-treatment Follow-up). 
Study Assessments
Efficacy Assessments
Mixed meal tolerance test (including urinary C-peptide), 72-hour continuous glucose 
monitoring, 7 point glucose profile, daily insulin usage, HbA1c, body weight, 
hypoglycaemia events, Audit of Diabetes Dependent Quality of Life (AddQoL) 
questionnaire
Safety assessments
Hypoglycaemia events, AE/SAEs (including AEs of special interest including DKA), 
pregnancy, clinical laboratory tests, immunogenicity, vital signs, 12-lead ECGs and 
physical examinations

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1.
INTRODUCTION
1.1.
Background
Epidemiology of Type 1 diabetes mellitus (T1DM)
Diabetes mellitus (DM) is a metabolic disorder characterised by chronic hyperglycaemia 
due to deficiencies in production of or response to the hormone insulin. Approximately 
382 million people have DM globally [IDF Diabetes Atlas, 2013].  A classification 
system developed by an international expert committee working under the sponsorship of 
the American Diabetes Association (ADA) recognises 4 types of DM: type 1 (T1DM; 
previously labelled Insulin Dependent Diabetes Mellitus or IDDM); type 2 (T2DM, the 
most common category, typically characterised by insulin resistance with relative insulin 
deficiency); gestational diabetes; and a final category that includes multiple specific but 
less common types of DM ([American Diabetes Association, 2014]. Patients with T1DM 
represent approximately 5% to 10% of all patients with DM.
T1DM is characterised by an absolute deficiency of insulin. The disease is classified in 
two subtypes: type 1a which includes the common, immune-mediated forms of the 
disease; and type 1b which includes non-immune forms [Concannon, 2009]. 
Approximately 85-90% of patients with T1DM have evidence of autoimmunity based on 
the presence of antibodies to islet cells, GAD, IA-2, IA-2β, and/or insulin. Patients with 
T1DM who lack evidence of autoimmunity are considered to have idiopathic T1DM, 
(type 1b). 
Pathophysiology of autoimmune T1DM
Type 1a diabetes is caused by the autoimmune destruction of pancreatic β cells, the only 
cells in the body that produce insulin. Insulin-producing pancreatic β cells are specifically 
targeted and progressively destroyed by activated, autoreactive CD4+ and CD8+ 
T effector cells [Ryden, 2007]. This autoimmune attack leads to the progressive loss of β-
cell function and endogenous insulin secretion culminating in an absolute dependence on 
exogenous insulin replacement therapy. T1DM is characterised by both increased 
background levels of glucagon and a paradoxical rise in glucagon levels in response to an 
oral glucose challenge [Kramer, 2013]. Both of these factors are likely to contribute to β-
cell stress and may therefore accelerate the decline in β-cell function seen in new onset 
T1DM (NOT1DM). 
The events triggering the development of an autoimmune attack on the β-cell are unclear. 
T1DM occurs most often in children, adolescents and young adults, but can present at 
any age. Although T1DM aggregates in some families, it does not segregate with any 
clear mode of inheritance reflecting a complex interaction between environment factors 
(such as viral infection) and inheritance  in determining individual risk of developing 
T1DM [Van Belle, 2011; Coppieters, 2011]. 
Clinical symptoms of T1DM do not develop until a significant portion of the β cell mass 
has been destroyed or compromised as a result of the autoimmune process [Tsai, 2006]. It 
is estimated that only 10-20% of β-cells are still functioning at the time of clinical 

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diagnosis [Knip, 2002] and β-cell function continues to decline after diagnosis. -cell 
function at the time of diagnosis is directly related to age, with younger patients tending 
to have less β-cell function at the time of diagnosis than older patients [Tsai, 2006; 
Bruno, 2005; Palmer, 2004; Porsen, 2007].  The rate of progression from normo-
glycaemia, through pre-clinical impairment of glucose handling to insulin dependence is 
variable. Indeed, even 1-5 years after diagnosis, about 50% of T1DM show clinically 
meaningful β-cell function [Palmer, 2009].
Unmet need in T1DM
There are currently no curative treatments for T1DM. The focus of existing treatment is 
on regulating blood glucose levels using exogenous insulin and a controlled diet. Even 
though insulin replacement therapy and other advances in the management of T1DM 
(including insulin pumps and continuous glucose monitoring) have improved the 
prognosis and quality of life of patients with T1DM, their mortality is still approximately 
2- to 10-fold higher than in the background population [Soedamah-Muthi, 2006]. 
Because of the lack of endogenous insulin production in T1DM, blood glucose levels are 
not regulated in a normal manner, and chronic hyperglycaemia and extreme fluctuations 
in glucose levels can occur. The resulting short term complications can include diabetic 
ketoacidosis (DKA) and hyperglycaemic coma and hypoglycaemia associated with 
insulin replacement therapy. In the long term suboptimal glycaemic control leads to an 
increased risk of microvascular complications involving the eyes, kidneys, and nerve 
tissue as well as macrovascular diseases such as atherosclerosis, coronary heart disease, 
stroke, and intermittent claudication. Patients with T1DM require long-term medical 
attention to limit and treat these complications.
For each individual patient with T1DM, the level of β-cell function is a critical factor in 
determining metabolic control and preventing complications [Palmer, 2004; Tsai, 2006]. 
It is well recognised in research and clinical practice that T1DM in patients with residual 
cell function (RBCF) is more stable and easier to manage, with less hyperglycaemia 
(including less DKA), less hypoglycaemia (including fewer serious episodes), and a 
lower exogenous insulin requirement [Ostman, 2000; Madsbad, 1979; Home, 2003; Kolb, 
2001; Palmer, 2004; Shima, 1977]. The Diabetes Control and Complications Trial 
(DCCT) and other studies have shown that patients with RBCF also have fewer long-
term vascular complications, including retinopathy and nephropathy [Steffes, 2003; 
DCCT, 1998; Fukuda, 1988; Gonen, 1979; Grajwer, 1977; Johansson, 2000; Ludvigsson, 
1977; Madsbad, 1980; Nakanishi, 1995; Sjoberg, 1991].
1.2.
Rationale
GLP-1 receptor agonists as disease-modifying therapies in T1DM
A clear need exists therefore, for therapies that can either affect the underlying 
pathophysiology of T1DM and/or help patients with established disease improve
glycaemic control and prevent complications. The incretin hormones, particularly 
glucagon-like peptide-1 receptor (GLP-1R) agonists, have the potential to do both.

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GLP-1R agonists (e.g., albiglutide, exenatide, liraglutide and lixisenatide) are therapeutic 
agents for the treatment of type 2 diabetes mellitus (T2DM) that stimulate insulin 
secretion in a glucose-dependent manner and suppress glucagon secretion, resulting in 
lower fasting plasma glucose and reduced postprandial glucose excursions with a low risk 
of hypoglycaemia. GLP-1R agonists also delay gastric emptying, increase satiety and are 
associated with modest weight reduction. These physiological effects of GLP-1 therapies 
may lead to an improvement in glycaemic control in subjects with T1DM as well as in 
those with T2DM. 
Preclinical studies in rodents, primarily in healthy and T2DM models, have shown that 
GLP-1R agonists stimulate transcription of genes important for glucose dependent insulin 
secretion and promote -cell neogenesis [Gautier, 2005]. As -cell function continues to 
decline following diagnosis of T1DM, these pre-clinical findings raise the possibility of 
using GLP-1R agonists early in the disease to help preserve the remaining -cell
function.
Pre-clinical evidence also suggests that GLP-1R agonists may positively impact on T cell 
function with respect to autoimmunity [Xue, 2008; Xue, 2010; Hadjiyanni, 2010; 
Bresson, 2009; Tooley, 2012]. It as yet unknown whether this will translate into a 
positive effect on cytotoxic T cell / T regulatory cell balance in humans, and hence have 
an effect on -cell survival.
The therapeutic potential of GLP-1R agonists in T1DM is supported by a small study 
comparing liraglutide with placebo in patients with T1DM. After 4 weeks of liraglutide 
treatment at doses approved for treatment of adults with T2DM, patients with residual -
cell function had lower HbA1c, lower insulin doses and less time spent with blood 
glucose < 3.9 mmol/L (assessed by continuous glucose monitoring) compared with those 
on placebo [Kielgast, 2011]. A reduction in HbA1c and insulin dose was also seen in 
subjects on liraglutide without residual -cell function with the reduction in insulin dose 
being positively correlated with -cell function at baseline.  There are also a number of 
small studies in subjects with established T1DM (with and without residual -cell 
function) which have demonstrated glycaemic benefits of the GLP-1R agonist exenatide 
[Ramen, 2010; Sarkar, 2014; Ghazi, 2014; Kielgast, 2011].  However no studies
assessing the effects of albiglutide in T1DM have been conducted to date.
The potential role of albiglutide in the treatment of T1DM
Albiglutide is a novel analogue of GLP-1 generated through a genetic fusion of 
2 modified recombinant human GLP-1 molecules linked in tandem to the amino terminus 
of recombinant human albumin. Albiglutide has been developed for the treatment of 
T2DM as an adjunct to diet and exercise, as monotherapy, or in combination with 
existing therapies. It has been approved by the EMA and the FDA as a treatment for 
T2DM. In a Phase III clinical trial, albiglutide in combination with insulin glargine was
shown as generally safe and efficacious in controlling HbA1c to target levels of <7.0% 
and <6.5%, in controlling fasting plasma glucose, favoured weight reduction and had
positive effects on the need for hyperglycemia rescue compared to meal time insulin 
lispro [Study GLP108486, GlaxoSmithKline Document Number; 2011N126139_00].

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This study seeks to evaluate the effect of albiglutide, compared to placebo, on 
endogenous insulin production and the preservation of -cell function (as measured by 
stimulated C-peptide following a mixed meal), in insulin treated subjects with NOT1DM 
and residual -cell function over one year. Albiglutide treatment will be added to a 
regimen of basal/meal-time insulin therapy. Insulin dose will be titrated according to a 
pre-defined algorithm with the aim of achieving equivalent glycaemic control in the 2 
treatment arms.  If albiglutide is able to preserve residual -cell function this could lead 
to less hyperglycaemia (including less DKA), less hypoglycaemia (including fewer 
serious episodes), a lower exogenous insulin requirement and ultimately in the long-term, 
fewer vascular complications.
The results of this proof of concept study will determine the next steps in the 
development of albiglutide as a novel, and potentially disease-modifying therapeutic in 
subjects with T1DM.
1.3.
Benefit:Risk Assessment
Albiglutide is in late stage development for T2DM and received regulatory approval for 
marketing on 27 Mar 2014 in the European Union and on 15 Apr 2014 in the United 
States.  This current study is for a new indication; subjects with NOT1DM and is the first 
study of albiglutide for this indication.  Therefore, the risk and benefit sections below 
have been derived from data and knowledge generated with albiglutide in subjects with 
T2DM. 
Within subjects with T2DM, albiglutide has been evaluated in a comprehensive global 
programme of studies involving approximately 9000 patient-years of overall exposure to 
date (including over 4000 patient-years of exposure to albiglutide). There have been 8 
well-controlled Phase III studies (including one study in subjects with concurrent renal 
impairment), ranging in duration from 32 weeks to 3 years, and using both 30 mg and 50 
mg once weekly dosing.  This programme has permitted a robust assessment of efficacy, 
safety, and tolerability in a representative T2DM population that spanned newly 
diagnosed subjects 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 
albiglutide can be found in the Investigator’s Brochure (IB) [GlaxoSmithKline Document 
Number; RM/2006/00602/07], any subsequent IB updates, and the product label. The 
following section outlines the risk assessment and mitigation strategy for this protocol.
1.3.1.
Risk Assessment
Key risks (identified and potential) associated with the use of albiglutide, or the GLP-1R 
agonist class, as well as the mitigation strategy for key risks of clinical significance are 
provided in the table below. Please refer to the IB [GlaxoSmithKline Document Number; 
RM/2006/00602/07] and any subsequent IB updates, for a thorough summary of the 
nonclinical and clinical experience with albiglutide as well as the complete Guidance for 
the Investigator (IB Section 6). In addition, the risks associated with study participation, 
study procedures or comparators are also included in the table.

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Identified/Potential/Other Risk of 
Clinical Significance
Data / Rationale for Risk
Mitigation Strategy
Investigational Product (IP): [albiglutide (GSK716155)] 
Pancreatitis
[Identified risk]
In clinical trials in T2DM, acute 
pancreatitis has been reported in 
association with albiglutide and other 
GLP-1R agonists (Refer to Section
5.4.5.2 and Section 6 of the IB).
Albiglutide has not been studied in 
patients with a history of pancreatitis 
to determine whether these patients 
are at increased risk of pancreatitis.
Specific eligibility and withdrawal  
criteria (See Section 4) 
Risk communication via Guidance 
For Investigators (IB Section 6)  and 
informed consent form for subjects
Gastrointestinal events
[Identified risks]
Albiglutide has not been studied in 
patients with severe GI disease, 
including severe gastroparesis 
Use of albiglutide and other GLP-1R 
agonists may be associated with GI 
AEs e.g., diarrhoea, nausea, vomiting 
(Refer to Section 5.4.5.4 and Section 
6 of the IB)..
Specific GI eligibility criteria (See 
Section 4) 
Risk communication via Guidance 
For Investigators (IB Section 6) and 
informed consent form for subjects
Blinded reduction of randomised
study medication in the event of GI 
intolerability (See Section 5.1.1)
Hypoglycaemia
[identified risk]
Albiglutide’s mechanism of action is 
associated with a low intrinsic risk of 
significant hypoglycaemia however, 
when used in combination with 
insulin or insulin secretagogues, the 
risk of hypoglycaemia is increased 
(Refer to Section 5.4.5.1 and Section 
6 of the IB).
Close monitoring for hypoglycaemia 
and need for intervention via frequent 
contact with subjects who will 
self-monitor plasma glucose (See 
Section 5.1.2).
Risk communication via Guidance 
For Investigators (IB Section 6)  and 
informed consent form for subject
Immunogenicity (e.g., clinical 
sequelae of antidrug antibodies, 
severe hypersensitivity reactions, 
other immune related events)
[identified risk]
In the Phase III programme in T2DM, 
approximately 5% of subjects 
developed anti-albiglutide antibodies 
but based on available clinical data, 
anti-albiglutide antibody formation is 
not expected to impact the overall 
safety or efficacy of albiglutide 
treatment (Refer to Section 5.6.1 of 
the IB).  
Although most patients with injection 
site reactions were antibody negative 
(approximately 85%), injection site 
reactions were reported more 
frequently for antibody positive 
(approximately 41%, than antibody 
negative patients, 14%). 
Hypersensitivity reactions are of 
potential concern with any injected 
protein and were reported rarely in 
the Phase III programme (Refer to 
Section 5.4.5.5 and Section 6 of the 
Specific eligibility and withdrawal 
criteria (See Section 4) 
Risk communication to subject via 
informed consent form. 
Prohibited concomitant medication of 
immunoglobulins (see Section 5.6.2.)

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Identified/Potential/Other Risk of 
Clinical Significance
Data / Rationale for Risk
Mitigation Strategy
IB).
Injection site reactions
[Identified risk]
Albiglutide is given as a 
subcutaneous (sc) injection in the 
abdomen, thigh, or upper arm and 
may cause pain, swelling, redness, 
and/or infection at the injection site
(Refer to Section 5.4.5.6 of the IB).
Risk communication via Guidance 
For Investigators (IB Section 6) and 
informed consent form for subject.
.
Patients will be advised that when 
injecting in the same region, to use a 
different injection site each week.  
Other adverse reactions
(e.g., pneumonia, atrial 
fibrillation/atrial flutter, appendicitis 
and hypersensitivity reactions)
[identified risks]
In the Phase III programme for 
T2DM, other adverse reactions were 
observed with a cumulative incidence 
< 3% in studies up to 3 years in 
duration (Refer to Section 5.4.5.10, 
Section 5.4.5.11 and Section 6 of the 
IB)
Risk communication via Guidance 
For Investigators (IB Section 6)  and 
informed consent form for subject
Regular ECGs (see Section 6)
Thyroid C-cell tumours
[potential risk]
This potential risk arises from non-
clinical rodent studies where GLP-1R 
agonists have been associated with 
increases in serum calcitonin, thyroid 
C-cell focal hyperplasia, and C-cell 
tumours. The relevance of these 
observations to man is uncertain. 
In phase III studies of up to 3 years 
duration, albiglutide was not 
associated with clinically relevant 
increases in serum calcitonin (Refer 
to Section 5.4.5.3 and Section 6 of 
the IB)..
Subjects with a personal or family 
history of MTC or Multiple Endocrine 
Neoplasia syndrome type 2 are 
excluded (see Section 4).
Risk communication via Guidance 
For Investigators (IB Section 6) and 
informed consent form for subject
Other malignant neoplasms (e.g., 
pancreatic cancer and malignancy 
when used with insulin)
[potential risk]
Theoretical concern pancreatic 
cancer associated with GLP-1 based 
therapies (DPPIV-inhibitors and GLP-
1R agonists) under evaluation by 
regulatory authorities (Egan; 2014), 
and has thus far concluded that a 
causal relationship cannot be 
established currently but they will 
continue to investigate as more data 
becomes available.
Theoretical concern raised by EU 
regulatory authorities based on the 
biological plausibility of a tumour-
promoting effect when a GLP-1R 
agonist is combined with insulin
No mitigation strategy

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Identified/Potential/Other Risk of 
Clinical Significance
Data / Rationale for Risk
Mitigation Strategy
Hepatotoxicity
[Potential risk]
One subject in the Phase III clinical 
programme developed probable drug 
induced liver injury with an 
asymptomatic elevation in ALT and 
total bilirubin although the cases had 
some atypical features and 
complicating factors. (Refer to 
Section 5.4.5.7 of the IB). 
Specific eligibility and withdrawal 
criteria (See Section 4).
Patient population with severe renal 
Impairment (eGFR 
< 30 mL/min/1.73 m2)o
[Other risk]
Experience of albiglutide in T2DM 
patients with severe renal impairment 
is very limited
Patients with severe renal impairment 
receiving albiglutide experienced a 
higher frequency of diarrhoea, 
nausea, and vomiting compared to 
patients with mild/moderate renal 
impairment (Refer to Section 5.4.6 
and Section 6 of the IB).  
Specific eligibility criterion (See 
Section 4).
Risk communication via Guidance 
For Investigators (IB Section 6) and 
informed consent form for subject
Drug Interactions
Albiglutide causes a delay in gastric 
emptying, and thereby has the 
potential to impact the absorption of 
concomitantly administered oral 
medications (refer to Section 5.2.1.2, 
Section 5.2.5, and Section 6 of the 
IB).
Drug interactions studies have been 
conducted with digoxin, warfarin, oral 
contraceptives, and simvastatin 
which demonstrated no clinically 
relevant PK or PD effects
Risk communication via Guidance 
For Investigators (IB Section 6) and 
informed consent form for subject
Pregnancy and Lactation
Studies in animals have shown 
reproductive toxicity. The potential 
risk to humans is unknown (Refer to 
Section 4.4.6 and Section 6 of the 
IB).
It is not known if albiglutide is 
secreted into human milk during 
lactation. Given that albiglutide is an 
albumin-based protein therapeutic, it 
is likely to be present in human milk
Decreased body weight in offspring 
was observed in mice treated with 
albiglutide during gestation and 
lactation.
Specific eligibility and withdrawal 
criteria (See Section 4)
Risk communication via Guidance 
For Investigators (IB Section 6) and 
informed consent form for subject.

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Identified/Potential/Other Risk of 
Clinical Significance
Data / Rationale for Risk
Mitigation Strategy
Study Design or Procedures 
Placebo-control
In subjects treated with placebo, 
hyperglycaemia may not improve or 
may worsen.
During the treatment period, the 
study will require individualisation of 
the insulin dose (both basal and 
meal-time insulin) in both treatment 
arms. (See Section 5.1.2.) aiming for 
euglycaemia
Albiglutide-placebo injection
In T2DM studies, albiglutide placebo 
injections were associated with a 
clinically relevant rate of injection site 
reactions (Refer to Section 5.4.5.6 of 
the IB)
Risk communication via Guidance 
For Investigators (IB Section 6) and 
informed consent form for subject.
.
Patients will be advised that when 
injecting in the same region, to use a 
different injection site each week
Other
Basal and meal-time Insulin 
Hypoglycaemia is the most common 
adverse effect associated with the 
use of insulins. The risk of 
hypoglycaemia increases with tighter 
glycaemic control (Refer to product 
labels).
Close monitoring for hypoglycemia 
and need for intervention via frequent 
contact with subjects who will 
self-monitor plasma glucose (See 
Section 5.1.2).
During the treatment period, the 
study will require individualisation of 
the insulin dose in both treatment 
arms with a treat-to-target approach 
and a titration regimen based on 
FPG. (See Section 5.1.2.)
Diabetic ketoacidosis (DKA)
DKA is a risk in patients with T1DM, 
especially NOT1DM, where subjects 
may be unfamiliar with insulin 
therapy, clinical presentation or risk 
of DKA and/or have an intercurrent 
illness.
Reduction of insulin dose to facilitate 
albiglutide treatment may 
theoretically increase the risk of DKA. 
Subjects will be regularly monitored 
for DKA during the study, educated 
on DKA and plasma glucose levels 
maintained within acceptable clinical 
ranges using insulin titration 
schemes outlined in Section 5.1.2.
Subjects advised to contact the site 
at any time with any concerns.
AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; CHMP = Committee for Medicinal 
Products for Human Use; DKA = diabetic ketoacidosis; eGFR = estimated glomerular filtration rate; EMA = European 
Medicines Agency; FDA = Food and Drug Administration; FPG = fasting plasma glucose; GI = gastrointestinal; GLP-1R 
= glucagon-like peptide 1 receptor; GSK = GlaxoSmithKline; IB = Investigator’s Brochure; ICF = informed consent 
form; LFT = liver function test; MTC = medullary thyroid carcinoma; PD = pharmacodynamic; PK = pharmacokinetic; 
SAE = serious AE; SC = subcutaneous; SU = sulfonylurea; ULN = upper limit of normal.
1.3.2.
Benefit Assessment
In subjects with T2DM, the clinical data showed that once weekly albiglutide treatment 
(both the 30 mg and 50 mg doses), in an easy-to-use pen device, resulted in clinically 
relevant lowering of HbA1c when given as monotherapy and in combination with 

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metformin, sulphonylureas, thiazolidinediones (TZD) and basal insulin (reference: IB 
Section 5.5). Furthermore, the durability of the effect on these glycaemic parameters was 
shown over a study period of 3 years. In the two Phase III studies that compared 
albiglutide to insulin treatment (i.e., insulin glargine in one study and insulin lispro in the 
other), albiglutide therapy was associated with approximately 1.5-to 2-fold less
symptomatic hypoglycaemia and with weight loss rather than weight gain (treatment 
difference of 1.5-2.6 kg). 
In this current study in NOT1DM, where albiglutide treatment will be added to a regimen 
of basal/meal-time insulin therapy, the subject is expected to achieve similar glycaemic 
control to the group taking insulin alone, but with a reduced total daily insulin dose, 
reduced glycaemic variability (hypoglycaemia and hyperglycaemia) and reduced weight 
gain. 
The anticipated benefit of albiglutide in NOT1DM is to delay or prevent deterioration of 
pancreatic β-cell function. Residual -cell function is important for patients because the 
clinical course of their diabetes tends to be more stable, easier to manage, with less 
hyperglycaemia (including less DKA), less hypoglycaemia (including fewer serious 
episodes), a lower exogenous insulin requirement [Ostman, 2000; Madsbad, 1979; Home, 
2003] and ultimately in the very long-term, fewer vascular complications [Steffes, 2003; 
DCCT, 1998], the latter will not be evaluated in this year-long study. 
Finally, as a result of participating in a clinical trial, each subject will receive more 
contact with the study site, have diet and exercise advice reinforced at each visit, and 
more enhanced supervision of their diabetes than would be performed as part of their 
usual standard of care.
1.3.3.
Overall Benefit:Risk Conclusion
Taking into account the measures taken to minimise risk to subjects participating in this 
study, the potential risks identified in association with albiglutide are justified by the 
anticipated benefits that may be afforded to patients with NOT1DM.
2.
OBJECTIVE(S)
2.1.
Primary Objective

Determine the effect of albiglutide therapy versus placebo on endogenous insulin 
secretion over 52 weeks when added to standard of care in subjects with new onset 
type 1 diabetes mellitus (NOT1DM).
2.2.
Secondary Objectives

To assess the effect of albiglutide versus placebo on plasma glucagon concentration 
during a mixed meal tolerance test (MMTT)

Determine the percentage of subjects meeting the definition of a responder (defined 
as having HbA1c ≤ 7.0% and mean daily insulin use < 0.5units/kg/day) and the 

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percentage of subjects achieving partial remission status (i.e., defined as subjects 
with Insulin Dose Adjusted A1c ( IDAA1C) 9.0)

To assess glycaemic control in both treatment groups as measured by HbA1c

Determine differences in total daily insulin dose between treatment groups

Determine any differences in significant hypoglycaemia (i.e., events with plasma 
glucose  < 3.9 mmol/L and/or requiring third party intervention) between treatment 
groups

Compare glycaemic variability between treatment groups, as measured by 72-hour  
continuous glucose monitoring (CGM) and 7 point glucose profile

Determine the effect of albiglutide on body weight

Assess the safety and tolerability of albiglutide in subjects with NOT1DM

To evaluate the albiglutide PK profile in subjects with NOT1DM
2.3.
Exploratory Objectives

Assess the effect of albiglutide on T1DM-associated auto-antibodies (antibody to 
glutamic acid decarboxylase (anti-GAD) antibody to protein tyrosine phosphatase-
like protein (anti-IA-2) and insulin autoantibody (IAA))

Explore whether urinary C-peptide could be used in future phase III studies as an 
alternative to plasma C-peptide AUC from mixed meal testing as a measure of 
endogenous insulin secretion

To evaluate the PK and PD (PK/PD) relationship between plasma albiglutide 
concentration and measures of glycaemic control (e.g., C-peptide, insulin use, 
HbA1c, etc) as data permit.  

To explore the PK/PD relationship between albiglutide and other potential efficacy,
tolerability (e.g., nausea and vomiting), and safety endpoints as data permit

Assess the effect of albiglutide on biomarkers associated with autoimmune 
pathology over 52 weeks in subjects with NOT1DM.

Assess the effect of albiglutide on diabetes-related quality of life as measured by the 
Audit of Diabetes Dependent Quality of Life questionnaire (ADDQoL).

Assess the effect of albiglutide on -cell function in the context of the prevailing 
glucose response to the MMTT
3.
INVESTIGATIONAL PLAN
3.1.
Study Design
This Phase II, randomised, double-blind, parallel group, placebo controlled, multicentre
study of 52 weeks treatment duration will evaluate the efficacy, safety and tolerability of 
weekly albiglutide versus placebo when added to insulin therapy in subjects with 

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NOT1DM and residual insulin production. The primary endpoint is mean change from 
baseline in mixed meal stimulated 2 hour plasma C-peptide AUC at Week 52.
Subjects within 8 weeks of diagnosis, who are receiving insulin treatment or have 
received insulin at some time between the date of diagnosis and the first dose of study 
drug, with one or more positive T1DM associated auto-antibodies, and a stimulated peak 
C-peptide > 0.2 nmol/L, signifying clinically relevant residual C-peptide production (as a 
measure of cell function), will be eligible to enter the study. 
After screening, approximately 68 eligible subjects will be randomised in a 3:1 ratio such 
that: 

51 subjects receive albiglutide 30 mg once weekly (with increase to 50 mg once 
weekly at Week 6 if the 30-mg weekly dose is tolerated) added-on to insulin
therapy

17 subjects receive placebo once weekly added-on to insulin therapy
During the study, subjects will perform self monitoring of plasma glucose at least 4 times 
daily and adjust their basal and meal-time insulin requirements according to protocol-
defined algorithm/guidance (See Section 5.1.2). 
The total duration of a subject’s participation will be approximately 72 weeks (up to 8
weeks of Screening, 52 weeks of treatment and 12 weeks of Post-treatment Follow-up)
(Figure 1). Subjects will have 12 study centre visits and at least 14 telephone calls. 
Figure 1
Study Schematic for GLP110933
Potential events of pancreatitis will be adjudicated by an independent pancreatitis 
adjudication committee (PAC).

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Subject completion is defined as completion of all periods of the study up to and 
including the follow-up period.
There will be no compassionate use of study medication once a subject completes or 
withdraws early from the study.
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 (Table 3), are essential and required for study 
conduct. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Procedures Manual (SPM). The SPM will provide 
the site personnel with administrative and detailed technical information that does not 
impact subject safety.

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3.2.
Discussion of Design
The design of this study and chosen endpoints i.e.,  randomised, double-blind, placebo-
controlled with primary endpoint assessment after one year in T1DM subjects with 
documented residual -cell function, are in line with guidance provided by both the EMA 
and FDA for the development of drugs aimed at preservation of cell function in T1DM 
[FDA, 2008; EMA, 2012].  Currently there are no approved treatments for preservation 
of -cell function in T1DM subjects. 
Endogenous insulin secretion, as a key measure of -cell function, is being assessed in 
this study by using the plasma C-peptide AUC following a mixed meal. When pancreatic 
cells produce insulin, they also produce C-peptide in equimolar amounts. C-peptide has 
a longer half life than insulin and unlike insulin, experiences little first pass clearance by 
the liver. C-peptide connects the two components of pro-insulin and is released when the
pro-hormone is activated [Gianani, 2005; Palmer, 2004]. Measurement of C-peptide 
under standardised conditions in response to a mixed meal challenge provides a sensitive, 
well accepted, and clinically validated assessment of endogenous insulin secretion and 
cell function [Palmer, 2004].
As indicated in the EU guidelines for developing drugs that preserve -cell function, 
pharmacological intervention will likely need to be initiated as soon as possible after 
manifestation of the disease to have a chance of showing a meaningful benefit (since 
greater than 80% of -cell function may have been lost by the time of diagnosis and it 
continues to decline after diagnosis). Accordingly, in this study, subjects are to 
commence treatment with study drug within 8 weeks of diagnosis. This time interval was 
selected as a balance between maximising the potential to preserve the remaining -cell 
function (by treating as early as possible after diagnosis) and feasibility (allowing time 
for subjects to consent to the study and to perform the screening assessments).
A stimulated C-peptide >0.2 nmol/L was selected as the cut-off for study entry as this 
level of C-peptide is the most widely used by researchers to represent clinically 
meaningful RBCF based on data from the DCCT [Diabetes Control and Complications 
Trial Research Group], 1998. The clinical importance of this cut-off was initially 
determined during the feasibility phase of the DCCT, in which metabolic parameters
including fasting and post-prandial glucose levels, HbA1c, and daily insulin dosage, were 
compared among patients with stimulated C-peptide levels in 4 categories: >0.2 nmol/L; 
>0.1 - 0.2 nmol/L; >0.05 - 0.1 nmol/L; and ≤0.05 nmol/L [DCCT, 1987]. The group with 
a C-peptide >0.2 nmol/L had statistically significantly lower values for all of these 
parameters (indicating better metabolic control) than the other 3 groups. In the larger 
DCCT study, patients with stimulated C-peptide >0.2 nmol/L at study entry had a 
reduced risk of retinopathy (or progression of retinopathy), microalbuminuria, and 
hypoglycaemia (including severe hypoglycaemia), and a lower HbA1c than patients with 
C-peptide <0.2 nmol/L [DCCT, 1998; DCCT, 1997].
The control arm of this study will be placebo.  To allow for a 3:1 randomisation ratio 
(albiglutide: placebo), historical data from the DEFEND-1 study [GlaxoSmithKline 
Document Number, 2011N125757_00] has been used as prior knowledge.  In DEFEND-
1, 53 subjects with similar inclusion/exclusion criteria were randomised to the placebo 

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group. Stimulated C-peptide data from a MMTT were collected at the same 52-week 
primary endpoint and therefore provide important safety and efficacy information for the 
placebo subjects. With this historical knowledge of placebo subjects, a Bayesian analysis 
method can be used which means fewer placebo subjects are required for this current 
study. 
Subjects in both arms of the study will be on background insulin therapy (or will have 
required insulin for more than 7 days since diagnosis) - the standard of care for T1DM.  
Insulin may be titrated up or down to maintain glycaemic control throughout the study 
according to treat-to-glycaemic target protocol-defined insulin titration algorithms.  
Observing the drug effect versus placebo on top of standard of care background therapy 
will allow a better understanding of the efficacy, safety and tolerability profile of 
albiglutide in NOT1DM.
Data from 8 Phase III studies in subjects with T2DM (GLP108486, GLP112753, 
GLP112754, GLP112755, GLP112756, GLP112757, GLP114179 and GLP114130) have 
confirmed that both albiglutide 30 mg and 50 mg demonstrated robust efficacy and were 
generally well-tolerated in this patient population. Although a 30 mg dose of albiglutide 
was effective at controlling glycaemia for at least 2 years in many T2DM subjects, an 
increase in dose to 50-mg weekly offered additional benefit without significant safety 
issues (See IB for further details).  The albiglutide dose in this study will start at 30-mg 
weekly and be increased to 50-mg weekly at Week 6 if the patient is able to tolerate the 
30 mg weekly dose.  Week 6 was chosen as the point for up-titration as it provides a 
sufficient length of time for subjects with NOT1DM to have their insulin doses stabilise 
and achieve steady-state exposures with 30 mg albiglutide (achieved following 4 to 5 
weeks of once-weekly administration).
Forced up-titration will allow a more homogenous evaluation of albiglutide at its highest 
approved dose (for the treatment of T2DM) without the confounding effects of dose and 
time. Hyperglucagonaemia can also occur in NOT1DM. Increasing the dose of 
albiglutide to 50 mg at Week 6 offers the opportunity to further reduce 
hyperglucagonaemia, hence minimising -cell stress.  The higher dose will therefore 
maximise the potential benefit of albiglutide treatment on endogenous insulin secretion in 
subjects with NOT1DM.  
Subjects experiencing GI intolerability on the 50 mg dose may decrease back to the 30 
mg dose following discussion between the investigator and the medical monitor.  This is 
included in the study design as it is important to keep subjects on albiglutide as long as 
possible to maximise the chance of being able to ascertain any therapeutic effect on cell 
function.
Glucose variability will be assessed by 2 methods - the 7 point glucose profile and 
continuous glucose monitoring (CGM). Whilst the 7 point glucose profile is the 
established method for assessing glucose variability in clinical practice and in studies, 
CGM is gaining popularity and is recommended for use in diabetes trials by the EMA as 
it provides more detailed information on variability (glucose is sampled every 5 mins for 
72 hours compared to the 7 point profile which only assesses glucose at 7 fixed time-
points over a 24 hour period). However, it is not yet fully validated, it can be subject to 

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technical failures, measures glucose in tissue fluid rather than plasma, must be calibrated 
with fingerstick blood glucose values several times a day and is more valuable in looking 
for trends than absolute values. Hence both measures are included in the protocol.
Subjects will return for a follow-up visit at Week 64 (12 weeks after the end of the 52-
week treatment period).  The purpose of this follow-up is to determine if the effect of 
albiglutide treatment on endogenous insulin secretion is still apparent 12 weeks after 
stopping treatment (thus suggesting that albiglutide is disease modifying). Subjects will 
continue to follow the insulin titration algorithm described in Section 5.1.2 until 
completion of the Week 64 follow-up visit, to ensure equivalent glycaemic control is 
maintained in the 2 treatment arms throughout the follow-up period.
4.
SUBJECT SELECTION AND WITHDRAWAL CRITERIA
4.1.
Number of Subjects
Approximately 68 subjects will be randomised to achieve 60 evaluable subjects.  Note: if 
the withdrawal rate from the study is larger than expected, consideration will be given to 
replacing subjects who withdraw from the study.
4.2.
Inclusion Criteria
Specific information regarding warnings, precautions, contraindications, adverse events, 
and other pertinent information on the GSK investigational product or other study 
treatment that may impact subject eligibility is provided in the IB/IB supplement(s), 
product label, add other pertinent documents.
Deviations from inclusion criteria are not allowed because they can potentially jeopardise 
the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, 
adherence to the criteria as specified in the protocol is essential.   
Subjects eligible for enrolment in the study must meet all of the following criteria:
1.
Male or female, aged 18 to 30 years, inclusive, with a diagnosis of T1DM with an 
interval of 28-56 days between the initial diagnosis and the first dose of study drug. 
Documentation of the diagnosis of T1DM (and not just insulin deficiency), including 
the date of diagnosis, must be obtained from the diagnosing physician.
2.
Currently requires insulin for T1DM treatment, or has required insulin therapy for 
T1DM (for 7 days) between the date of diagnosis and the first dose of study drug
Note: subjects currently taking twice daily commercially available pre-mixed insulin 
will not be eligible.
3.
Positive for at least one of the following autoantibodies typically associated with 
T1DM: antibody to glutamic acid decarboxylase (anti-GAD) antibody to protein 
tyrosine phosphatase-like protein (anti-IA-2) or an insulin autoantibody (IAA).

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Please note: A subject who is positive for IAA and negative for the other 
autoantibodies will not be eligible if the subject has been using insulin for a total of 
7 days.
4.
Evidence of residual functioning pancreatic β-cells as measured by a peak stimulated 
C-peptide level > 0.20 nmol/L during the Screening MMTT when plasma glucose 
level is > 3.9 mmol/L (70 mg/dL) and ≤ 11.1 mmol/L (200 mg/dL).
Note: the Screening MMTT should not be performed within one week of resolution 
of a DKA event.
5.
Body mass index ≤ 32.0 kg/m2.
6.
Female subjects of childbearing potential (i.e., not surgically sterile and/or not 
postmenopausal) must be practicing adequate contraception (i.e., meeting one of the 
criteria defined below) from at least 14 days prior to the first dose of randomised 
study medication until the 12-week post-treatment Follow-up visit

Abstinence from penile-vaginal intercourse, when this is the female’s preferred 
and usual lifestyle 

Oral Contraceptive, either combined or progestogen alone

Injectable progestogen

Implants of etonogestrel or levonorgestrel

Estrogenic vaginal ring

Percutaneous contraceptive patches

Intrauterine device or intrauterine system that has a failure rate of less than 1% 
per year when used consistently and correctly as stated in the product label

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 the site personnel’s review of subject’s medical records; 
medical examination of the subject and/or semen analysis; or interview with the 
subject on his medical history.

Male condom combined with a female diaphragm, either with or without a 
vaginal spermicide. [UK only: this method of contraception is acceptable only if 
used with a vaginal spermicide]. 
7.
Able and willing to provide written informed consent and to comply with all study 
procedures.
4.3.
Exclusion Criteria
Deviations from exclusion criteria are not allowed because they can potentially 
jeopardise the scientific integrity of the study, regulatory acceptability or subject safety. 
Therefore, adherence to the criteria as specified in the protocol is essential. 
Subjects meeting any of the following criteria must not be enrolled in the study:

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1.
Severe gastroparesis i.e., requiring therapy within 6 months prior to Screening
2.
History of acute or chronic pancreatitis, or considered clinically at significant risk of 
developing pancreatitis, during the course of the study (e.g. due to symptomatic 
gallstones, excess alcohol use).
3.
History of significant gastrointestinal surgery that in the opinion of the investigator is 
likely to significantly affect upper gastrointestinal or pancreatic function (e.g. gastric 
bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel 
resection, or surgeries thought to significantly affect upper gastrointestinal function)
4.
Personal history or family history of thyroid medullary carcinoma or multiple 
endocrine neoplasia type 2 (MEN2)
5.
History of cancer that has not been in full remission for at least 3 years before 
Screening. (A history of squamous cell or basal cell carcinoma of the skin, or treated 
cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)
6.
Fasting triglyceride level >750 mg/dL at Screening.  Subjects may be re-tested once 
during screening, and if the value no longer meets the exclusion criterion, the subject 
can be randomly assigned to treatment
7.
Estimated Glomerular Filtration Rate (eGFR) 30 mL/min/1.73 m2 (calculated using 
the Modification of Diet in Renal Disease (MDRD) formula
8.
Haemoglobinopathy that may affect proper interpretation of HbA1c
9.
Alanine aminotransferase (ALT) >2.5 × upper limit of normal (ULN) and bilirubin 
>1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated 
and direct bilirubin <35%)
10. Unstable liver disease (as defined by the presence of ascites, encephalopathy, 
coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent 
jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert’s 
syndrome or asymptomatic gallstones). [Chronic stable hepatitis B and C are 
acceptable if subject otherwise meets entry criteria and are not on active antiviral 
treatment (e.g., presence of hepatitis B surface antigen or positive hepatitis C test 
result within 3 months of screening)]
11. Any clinically significant co-morbidity or abnormality (including psychiatric 
disorder, any other autoimmune endocrinopathy e.g., primary autoimmune 
hypothyroidism, hypoadrenalism, coeliac disease etc) that in the opinion of the 
Investigator, may pose additional risk in administering study medication or trial 
participation
12. Female subject is pregnant (confirmed by laboratory testing) or lactating
13. Known allergy to any GLP-1 analogue, insulin, or excipients of albiglutide
14. Treatment with any oral anti-diabetic medication within the prior 30 days or 5 half-
lives of that medication, whichever is longer.
15. Use of immunosuppressants, intravenous immunoglobulin, oral or systemically 
injected glucocorticoids within the 3 months before randomisation or high likelihood 
of a requirement for prolonged treatment (>1 week) in the year following 
randomisation. However, short courses of oral steroids (single dose or multiple doses 

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for up to 7 days) may be permitted provided these cases are discussed with the 
medical monitor. Inhaled, intra-articular, and small quantities of non-potent topical 
corticosteroids are allowed
16. Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is 
longer, before Screening, a history of receipt of an investigational anti-diabetic drug 
within the 3 months before randomisation, or receipt of albiglutide in previous 
studies
4.4.
Withdrawal Criteria
Any subject who discontinues randomised study medication for any reason, after 
receiving at least one dose, will be asked to remain in the study and attend selected visits 
(see below) for collection of long-term efficacy and safety data (i.e., withdrawal of study 
drug does not require withdrawal from the study).
Every effort should be made to keep subjects in the study. The reasons for subjects 
discontinuing study medication and/or not completing the study will be recorded. 
Consideration will be given to replacing subjects who withdraw from the study.
Reasons for study drug discontinuation

These AEs will require study drug withdrawal:
o
Elevation of liver function test results according to the criteria in Section
6.4.9, 
o
Severe allergic/hypersensitivity reactions that are considered by the 
investigator to be attributable to randomised study medication or without a 
likely alternative etiology (see Section 6.4.14)
o
Confirmed acute or chronic pancreatitis (see Section 6.4.15)
o
Confirmed medullary thyroid cancer

AE, which, in the opinion of the investigator or subject precludes continuation 
of dosing

Loss to follow-up (the investigator must make every effort to contact subjects 
lost to follow-up)

Study closed/terminated or Investigator site closed

Pregnancy or intention of becoming pregnant

Protocol deviation (the investigator should discuss the protocol deviation with 
the sponsor before withdrawing study drug)

Subject decision (reason to be documented in the electronic case report form 
(eCRF), if specified by the subject)

Investigator discretion

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Subjects who discontinue study medication will be asked to continue to attend the study 
visits where a MMTT is performed through to Week 64 (i.e., Week 16, Week 28, Week 
52 and Week 64).  During these visits where a MMTT will be performed, HbA1c, 
weight, AEs, hypoglycaemia and insulin usage will also be assessed. Subjects will also 
be asked to continue completing diaries for insulin usage and hypoglycaemia events.  
Additionally, the insulin titration algorithm/guidelines should continue to be followed 
through to Week 64.
While participating in the study, subjects should not receive any additional antidiabetic 
medication (except insulin) or investigational agents until after the Week 64 visit.
Reasons for withdrawal from the study

AE which precludes continued follow-up in the study.  Note: All AEs and SAEs 
will be followed until resolution, until the condition stabilises, or until the subject is 
lost to follow-up as described in the SPM. 

Lost to follow-up (the investigator must make every effort to contact subjects 
lost to follow-up).

Study closed/terminated or Investigator site closed

Protocol deviation (the investigator should discuss the protocol deviation with 
the sponsor before withdrawing a subject).

Subject decision (reason to be documented in the eCRF, if specified by the 
subject)

Investigator decision (e.g., in the investigator’s opinion, continuation in the 
study would be detrimental to the subject’s well-being).
Note: Use of a prohibited medication constitutes a protocol deviation. Continuation of 
the subject in the study will be discussed with the medical monitor and the decision of 
continuation or withdrawal will be documented.
Should a subject fail to attend the clinic for a required study visit, the site should attempt 
to contact the subject and re-schedule the missed visit as soon as possible. The site should 
also 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 based 
on previous non-compliance. In cases where the subject does not return for the 
rescheduled visit or cannot be reached to reschedule the missed visit, the site should 
make every effort to regain contact with the subject (3 telephone calls and if necessary a 
certified letter to the subject’s last known mailing address) so that they can appropriately 
be withdrawn from the study. These contact attempts should be documented in the 
subject’s medical record. Should the subject continue to be unreachable, then and only 
then will he/she be considered to have withdrawn from the study with a primary reason of 
“Lost to Follow-up”. For all other subjects withdrawing from the study, an alternative 
reason for discontinuation should be recorded in the eCRF.
Subjects will be considered withdrawn from the study if they stop participating in the 
study and no longer attend visits. Each subject who withdraws should have an early 
withdrawal visit as soon as possible after deciding to withdraw. The assessments to be 

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performed at the early withdrawal visit are specified in the Time and Events Table 
(Table 3).
The half-life of albiglutide is approximately 5 days, and significant therapeutic 
concentrations can persist for up to 5 half-lives (3 to 4 weeks) after discontinuation. 
Therefore, the investigator should use caution when prescribing treatment after the 
withdrawal of active study medication taking into consideration the long half-life of 
albiglutide (see Section 5.6.2 for prohibited anti-diabetic medications for subjects 
discontinuing study medication early but still participating in the study), taking into 
consideration the long half-life of albiglutide. 
4.5.
Screening/Run-in Failures
Screen failures are defined as subjects who consent to participate in the clinical trial but 
are never subsequently randomised.  In order to ensure transparent reporting of screen 
failure subjects, meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements, and respond to queries from Regulatory authorities, a minimal 
set of screen failure information will be collected including Demography, Screen Failure 
details, Eligibility Criteria, and any Serious Adverse Events.
5.
STUDY TREATMENTS
5.1.
Investigational Product and Other Study Treatment
Albiglutide (and albiglutide matching placebo) will be provided as a fixed-dose, fully 
disposable pen injector system for delivery of the investigational product from a prefilled 
dual chamber glass cartridge that is an integral part of the pen. The pen is intended for 
single use by the subject. It is designed for manual reconstitution of the dose, priming and 
insertion of the pen needle, and manual injection by the subject. 
Albiglutide (or albiglutide matching placebo) is intended for self-administration as a 
subcutaneous (sc) injection in the abdomen, thigh or upper arm region. The pen includes 
a mechanical locking system that prevents the user from manipulating the dose button 
before the cartridge has been fully reconstituted. Reconstitution is performed through 
rotation of the pen housing parts. The pen is designed to work with standard pen needles.
When the injector pen product is reconstituted by the subject, a neutral, isotonic solution 
is produced. The pens will deliver either 30 mg of albiglutide, 50 mg of albiglutide, or 
albiglutide placebo in a 0.5-mL injection volume.
The contents of the label will be in accordance with all applicable regulatory 
requirements.
Under normal conditions of handling and administration, investigational product 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. Notify the monitor of 
any unintentional occupational exposure.  A Material Safety Data Sheet (MSDS) 

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describing the occupational hazards and recommended handling precautions will be 
provided to site staff if required by local laws or will otherwise be available from GSK 
upon request.
The investigational product (albiglutide and albiglutide-matching placebo) must be stored 
in a secure area at 2°C to 8°C and protected from freezing. Each site must maintain a 
temperature log.  Access to the investigational product will be limited to the investigator 
and authorised site staff (investigator or designee).  Investigational product must be 
dispensed or administered only to subjects enrolled in the study and in accordance with 
the protocol.
Procedures for the disposal of unused study treatment will be provided in the SPM.
Concomitant Insulin treatment
Concomitant insulin treatment (basal and meal-time insulin) should be used according to 
Section 5.1.2 but will not be provided by GSK.  Subjects should be instructed on the use 
and storage requirements for insulin and will administer insulin as prescribed by their 
physician and in accordance with the package insert.
5.1.1.
Investigational Product Administration During the Treatment
Period
Investigational product (albiglutide or albiglutide matching placebo) will be administered 
once weekly by sc injection in the abdomen, thigh or upper arm region, from Baseline 
through to Week 52. The starting dose of albiglutide will be 30 mg once weekly and will 
be increased at Week 6 to 50 mg once weekly if the 30-mg weekly dose is tolerated. 
Subjects randomly assigned to albiglutide matching placebo will also go through the 
increased dose procedure to maintain study blind.
Note: if a subject experiences tolerability issues due to gastrointestinal AEs (e.g., nausea, 
vomiting or diarrhoea), the investigator should discuss the case with the medical monitor 
and a decision to decrease the dose back to 30 mg once weekly may be made.  
Decreasing the dose because of hypoglycaemia should not occur, the insulin dose should 
be adjusted instead.
Albiglutide (or albiglutide matching placebo) may be administered at any time of day 
without regard to meals. It should be administered once a week on the same day each 
week. The day of weekly administration can be changed if necessary provided the last 
dose was administered 4 days previously. If a dose is missed, it should be administered 
as soon as possible within 3 days after the missed dose. Thereafter, subjects can resume 
dosing on their usual day of administration. If it has been > 3 days since the missed dose, 
subjects should wait and administer their next regularly scheduled weekly dose.  
If a subject misses 2 consecutive doses, the investigator should contact the medical 
monitor (with details on why the doses were missed). The medical monitor will decide
(on a case by case basis) whether the subject should be withdrawn from the study for a 
protocol deviation.

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5.1.2.
Insulin Titration
Subjects will take insulin as prescribed by the investigator throughout the study from 
Screening through to the follow-up visit.  Note: subjects currently taking twice daily 
commercially available pre-mixed basal and meal-time insulin will not be eligible for the 
study.
It is important to ensure that subjects in both groups receive appropriate glycaemic 
control up to and including the follow-up visit (Week 64).  All subjects should self 
monitor their plasma glucose values as detailed in Section 6.3.2.2. The investigator will 
provide guidance and education on the insulin regimen according to local clinical practice 
and will recommend dose adjustments at the regular study visits/telephone calls
following the algorithm and guidance provided in Section 5.1.2.1 and Section 5.1.2.2 and 
based on the subject’s self monitored plasma glucose values.  
However, it is important that the Investigator base the decision to adjust the insulin dose 
on all available information, hypoglycaemia and/or hyperglycaemia (regardless of 
symptoms), urine ketone testing, previous responses to dose adjustments and plasma 
glucose measurements.  Basal and meal-time insulin should be titrated up or down 
according to the algorithm/guidance in Table 1 and Table 2 to maintain equivalent 
glycaemic control in both treatment groups throughout the study. The investigator should 
communicate with the medical monitor if there is any doubt on insulin dose adjustment.
NOTE: the use of a GLP-1R agonist, (albiglutide) is expected to decrease the need 
for exogenous insulin. Therefore, the investigator will need to ensure careful follow-
up of each subject accordingly, particularly during the first few weeks of treatment 
and reduce insulin doses if the subject experiences hypoglycaemia or there is a 
significant risk of hypoglycaemia.
Telephone calls (if there is no scheduled study visit) must take place at least weekly 
between the investigator and subject from Baseline to Week 16, as well as at Week 
22, Week 34 and Week 46, and as required until the end of the follow-up phase, in 
order to optimise insulin titration. It is recommended that the investigator calls the 
subjects every 3-5 days during the first 2 weeks of randomised therapy and for 2 
weeks after Week 6 when the study drug dose is increased.  The investigator should 
consider increasing the frequency of telephone calls to optimise insulin titration if 
the subject’s glycaemic control is erratic, or if there are associated clinical 
conditions that may impact on glycaemic control.
Subjects should be advised that they may contact the site at any time they would like 
advice or guidance on insulin dose adjustments or any concern about possible 
glycaemic and metabolic complications such as hypoglycaemia or ketoacidosis in 
particular.
Additionally, subjects should check their urine frequently, as directed by the study 
investigator, with Ketostix against the colour chart provided in line with usual clinical 
practice and seek medical attention as appropriate. The following guidance is provided:

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
If the Ketostix identifies a small amount of urinary ketones and the subject is 
otherwise well, this may be associated with a period of fasting, or the subject may 
need to increase their insulin dose slightly 

If the Ketostix identifies a moderate or large amount of ketones, particularly if the 
plasma glucose is elevated, or the subject is unwell with an intercurrent illness, this 
may indicate DKA.  The subject should seek urgent medical advice, either by 
telephone or in person from the physician who normally manages their T1DM or 
acute medical services if their regular physician is unavailable
Note: nausea and vomiting may be side-effects associated with albiglutide treatment 
but may also be symptoms of DKA.  Subjects should be advised to check their urine 
more frequently during episodes of nausea and vomiting and to seek medical 
attention as appropriate.
5.1.2.1.
Basal Insulin Titration
Both treatment arms will follow the same basal insulin titration algorithm during the 
treatment period.
In the absence of fasting plasma glucose (FPG) <4.1 mmol/L in the previous week, or a 
nocturnal hypoglycaemia event, adjustment of basal doses should be as described in 
Table 1. It should be based on the mean (or single value if only 1 is available) of the 
subject’s self-monitored plasma glucose values measured before breakfast on 2 
consecutive days in the week before the study visit/telephone contact, as shown in 
Table 1.  At the investigator’s discretion, basal insulin dose may be temporarily 
discontinued.
Table 1
Titration Algorithm for Basal Insulin
Before Breakfast Plasma Glucose1
Adjustment of Basal Insulin (U)
mmol/L
mg/dL
<3.12
<562
-4
3-1 – 4.03
56 - 723
-2
>4.0 – 5.5
>72 – 99
No adjustment
>5.5 –7.8
>99 – 140
+2
>7.8
>140
+4
1.
Mean of 2 or more consecutive days’ measurements in the previous 7 days.
2.
Investigator may defer adjustment if there is an obvious reason for the low value such as a missed meal or may 
interrupt or temporarily discontinue insulin, if appropriate.
5.1.2.2.
Meal-time Insulin Titration
Meal-time insulin dose adjustment cannot be fully corrected, unless basal insulin doses 
have been optimised as far as possible. Both treatment arms will follow the same meal-
time insulin titration guidance during the treatment period (Table 2). However, this is 
provided as guidance only as the meal-time insulin dose will be contingent upon, in 
particular, the planned carbohydrate caloric consumption, physical activity level, and the 
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The dose adjustment of meal-time insulin is based on the plasma glucose values 4 
hours after the previous meal. It is recommended that dose adjustments of meal-time 
insulin be made on the mean (or single value if only one available) of values from 2 
consecutive days in the week just prior to the visit/phone contact as outlined in Table 2. 
At the investigator’s discretion, bolus insulin at one or more meal-times may be 
interrupted.
Table 2
Titration Guidance for Meal-time Insulin
Plasma glucose 4 or more hours after the preceding meal1, 2
Adjustment of meal-time insulin 
(U)2
mmol/L
mg/dL
<3.9 without obvious explanation
<70 without obvious explanation
-1-23
3.9 – 5.5
70 – 99
No adjustment
5.6 – 7.7
100 – 139
+1
7.8 – 9.9
140 – 179
+2
10.0
180
+3
1.
If basal dose is not optimal following this algorithm may lead to overdosing
2.
Mean of 2 or more consecutive days’ measurements over previous 7 days
3.
At the investigator’s discretion, a meal-time insulin dose may be suspended
It is strongly recommended that the algorithms in Table 1 and Table 2 are followed at all 
visits and telephone contacts until the Week 64 Follow-up visit. Any deviation from the 
algorithm and the detail of reasons for this deviation must be recorded by the 
Investigator. Any deviation that does not have a valid reason will be recorded as a 
protocol deviation. 
5.1.3.
Surveillance of Insulin Titration
Surveillance of insulin titration will be performed centrally. Within approximately 
24 hours after a subject’s study visit/telephone contact, the Investigator must ensure that 
the following data are available for review by the medical monitor:

Subject’s self-monitored plasma glucose (SMPGs) on 2 consecutive days in 
the week prior to the visit/telephone contact

Insulin doses on 2 consecutive days in the week prior to the visit/telephone 
contact

Insulin doses recommended until the next visit/telephone contact

Comments on any deviation to the titration algorithm/guidance
The data regarding titration deviations will be reviewed by the medical monitor. Based on 
this information, an inquiry as to why the Investigator chose to deviate from the titration 
algorithm may be made – in particular details of any SMPG readings, time, and date, or 
hypoglycaemic symptoms, used in such a decision are needed. Not all deviations will 
lead to inquiry. When the Investigator receives an inquiry, a response with the reasons for 
not adhering to the titration guideline should be received within approximately 3 days. 
Depending on the response additional inquiries may be sent.

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5.2.
Treatment Assignment
Subjects will be assigned to study treatment in accordance with the randomisation 
schedule.
Randomised treatment assignment will be done via the interactive voice response system 
(IVRS), and randomisation will be implemented based on a sequestered fixed 
randomisation schedule. Study centre personnel will call the IVRS to execute each 
randomisation and initiate shipment of the investigational product once a subject has met 
all prerequisites for randomisation and has completed all scheduled screening procedures. 
Approximately 68 subjects will be randomly assigned to 1 of the following 2 treatment 
groups in a 3:1 ratio such that

Approximately 51 subjects are assigned to albiglutide 30 mg weekly (with 
treatment-masked increase to 50 mg weekly at Week 6) + background insulin

Approximately 17 subjects are assigned to albiglutide matching placebo + 
background insulin
Blinded study centre personnel will receive a randomisation notification indicating only 
the unique subject identifier and the date and time of randomisation. Each subject number 
will be a unique identifier. Once a subject number has been assigned, the number will not 
be reused even if the subject withdraws before receiving any investigational product. 
Details of the treatment assignment process are contained in the SPM.
5.3.
Blinding
This will be a double-blind study.  Study treatment with albiglutide and matching 
albiglutide placebo is blinded to subjects, study personnel and sponsor.
The investigator or treating physician may unblind a subject’s treatment assignment only 
in the case of an emergency or in the event of a serious medical condition, when 
knowledge of the study treatment is essential for the appropriate clinical management or 
welfare of the subject, as judged by the investigator.  Investigators have direct access to 
the subject’s individual study treatment.  It is preferred (but not required) that the 
investigator first contacts the GSK Medical Monitor or appropriate GSK study personnel 
to discuss options before unblinding the subject’s treatment assignment.  If GSK study 
personnel are not contacted before the unblinding, the investigator must notify GSK as 
soon as possible after unblinding, but without revealing the treatment assignment of the 
unblinded subject, unless that information is important for the safety of subjects currently 
in the study.  The date and reason for the unblinding must be fully documented in the 
appropriate data collection tool.
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
treatment assignment for any subject with an SAE.  If the SAE requires that an expedited 
regulatory report be sent to one or more regulatory agencies, a copy of the report, 
identifying the subject’s treatment assignment, may be sent to clinical investigators in 
accordance with local regulations and/or GSK policy.

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If a subject is unblinded, withdrawal of that subject from study treatment/study will be at 
the discretion of the investigator.
5.4.
Product Accountability
In accordance with local regulatory requirements, the investigator, designated site staff, 
or head of the medical institution (where applicable) must document the amount of 
investigational product dispensed and/or administered to study subjects, the amount 
returned by study subjects, and the amount received from and returned to GSK, when 
applicable.  Product accountability records must be maintained throughout the course of 
the study.
5.5.
Treatment Compliance
Investigational product accountability will be done for albiglutide/matching placebo at 
each study visit after the baseline visit through the end-of-treatment visit (at Week 52) 
inclusive. Subjects will be instructed to return all unused investigational product and used 
injector pens at each visit (with the exception of Week 2 where only used injector pens 
need to be returned) in order to perform drug accountability and determine compliance. 
Acceptable overall compliance for this study will be 80% for albiglutide and albiglutide 
matching placebo. 
If a subject misses 2 or more consecutive doses of randomised study medication, the 
investigator should contact the medical monitor, who will make a decision (on a case by 
case basis) on whether the subject should be withdrawn from study drug or the study for 
non-compliance.
Background insulin will be taken as prescribed by the investigator and in accordance with 
the respective package insert.
5.6.
Concomitant Medications and Non-Drug Therapies
All concomitant medications taken during the study will be recorded in the eCRF. The 
minimum requirement is that drug name and the dates of administration are to be 
recorded.
5.6.1.
Permitted Medications and Non-Drug Therapies
Note: Albiglutide causes a delay of gastric emptying, and thereby has the potential to 
impact the absorption of concomitantly administered oral medications. During the 
development programme, drug interaction studies were conducted with digoxin, warfarin, 
oral contraceptives, and simvastatin which demonstrated no clinically relevant 
pharmacokinetic or pharmacodynamic effects (see GlaxoSmithKline Document Number, 
RM/2006/00602/07). However, investigators should use clinical judgement and caution 
when prescribing concomitant medications.

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The following are permitted:

Insulin
Insulin use will be recorded in diaries by subjects, as described in the Time and Event 
Table (Table 3) and Section 6.3.2.5. The insulin-use data will be reviewed by the 
investigator for accuracy and completeness. Subjects should use a basal/bolus insulin 
regimen. Insulin pumps and twice daily commercially available pre-mixed insulin are 
not permitted. Insulin dosage may be changed and insulin therapy may be interrupted 
or re-started whenever necessary to help the subject achieve and maintain optimum 
glycaemic control. See Section 6.2 for description of diabetic standard of care.

As-needed use of other prescription and over-the-counter medications at the 
discretion of the investigator
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.
Investigators must adhere to the local labeling of the respective country (e.g., the 
summary of product characteristics in relevant European countries) for all non-excluded 
medications.
5.6.2.
Prohibited Medications and Non-Drug Therapies
Subjects must not use any of the following medications:

Twice daily commercially available pre-mixed insulin.

Insulin pumps.

Anti-diabetic medications other than insulin and the treatment they have been 
randomly assigned to (Note: even if a subject discontinues randomised study 
medication, he/she should not receive any other GLP-1R agonist, oral anti-
diabetic medication (e.g., metformin, sulphonylurea, thiazolidinediones, 
Dipeptidypeptidase-IV [DPP-4]) or an investigational agent until after the Week 
64 visit)

Immunosuppressants and intravenous immunoglobulin

Prescription and over-the-counter weight loss drug

Prolonged treatment (>1week) of oral or systemically injected glucocorticoids
If a subject receives a prohibited medication, a protocol deviation will be reported and 
continuation in the trial will be discussed with, and agreed upon, by the medical monitor.
5.7.
Treatment after the End of the Study
After completion of the Week 52 visit, subjects will stop randomised study medication.  
Subjects will continue to receive insulin therapy (basal-bolus insulin) as prescribed by 
their health care provider but must continue to adhere to the protocol-defined insulin 

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titration algorithm/guidelines until Week 64.  Subjects will return to the study centre at 
Week 64 for the follow-up visit and will have then completed the study.
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the patient’s medical condition whether or not GSK is providing specific 
post study treatment.
5.8.
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 sc 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).
Excess insulin administration may cause hypoglycaemia and hypokalaemia. If an 
overdose of insulin occurs, the investigator should consult the approved product label for 
advice. Subjects should be watched closely even after treatment of the acute event; 
recurrence should be managed appropriately
6.
STUDY ASSESSMENTS AND PROCEDURES
This section includes a brief description of each planned study assessment. The exact 
timing of each assessment is listed in the Time and Events Table (Table 3) and the 
schedule of telephone calls is listed in Table 4. Detailed procedures for obtaining each 
assessment are provided in the SPM.

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Table 3
Time and Events Table
Study Procedure
Screening
Treatment
To include at least weekly telephone contact (where there is no 
study visit) from Baseline to Week 16 – see Table 4 2
Off 
treatment 
follow-up
Early 
Withdra
w27
Baseline
Visit
1
23
3
4
5
6
7
8
9
10
11
12
Week1
-8 to 0
0
2
4
6
8
16
28
40
52
64
Written informed consent
x
Demography and history (medical, disease, therapy)
x
Review eligibility criteria
x
x
x
Provide diet, exercise and home glucose monitoring 
advice
x
x
x
x
x
x
x
x
x
x
Efficacy assessments
Mixed meal tolerance test4
x
x
x
x
x
7 point glucose profile5
x
x
x
72 hour continuous glucose monitoring 6
x
x
x
Review glucose monitoring/insulin dose with subject
x
x
x
x
x
x
x
x
x
x
x
ADDQoL
x
x
Safety assessments
Concomitant medication
x
x
x
x
x
x
x
x
x
x
x
x
x
Physical examination7
x
x
x
x
x
x
x
x
Vital sign8
x
x
x
x
x
x
x
x
x
x
x
x
12-lead ECG9
x
x
x
x
x
x
x
Adverse events
X10
X10
x
x
x
x
x
x
x
x
x
x
x
Assess for hypoglycaemic events11
x
x
x
x
x
x
x
x
x
x
x
x
Laboratory assessments
HbA1c
x
x
x
x
x
x
x
x
x
Triglycerides (fasting)12
x
T1DM associated auto-antibody titres13
x14
x
x
x
x
x
x
Immunogenicity 15
x
x
x
x
x
x
x
x
x
x
Haematology16/chemistry17
x
x
x
x
x
x
x
x
x
x18
x
Urinalysis19
x
x
x
x
x
x
x
x
x18
x
Pharmacogenetics20
x
Pharmacokinetic sample21
x
x
x
x
PBMC Biomarker sample 22
x
x
x
x
x
x
x

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Study Procedure
Screening
Treatment
To include at least weekly telephone contact (where there is no 
study visit) from Baseline to Week 16 – see Table 4 2
Off 
treatment 
follow-up
Early 
Withdra
w27
Baseline
Visit
1
23
3
4
5
6
7
8
9
10
11
12
Week1
-8 to 0
0
2
4
6
8
16
28
40
52
64
Serum Biomarker sample 23
x
x
x
x
x
x
x
Pregnancy test24
U
U
U
U
U
U
U
U
U
U
HBsAg, and hepatitis C antibody25
x
Dispense Investigational product (IP)
x
x
x
x
x
x
x
IP compliance
x
x
x
x
x
x
x
x
x
Register visit into IVRS26
x
x
x
x
x
x
x
x
x
x
x
x
x
ADDQoL = audit of diabetes dependent quality of life; ECG = electrocardiogram; HbA1c = glycosylated haemoglobin, HBsAg =-hepatitis B surface antigen ;IVRS = interactive voice 
response system, PGx = pharmacogenetics; S = serum; U = urine, PBMC = peripheral blood mononuclear cells; T1DM = type 1 diabetes mellitus
1.
Study visits from Baseline through to Week 8 will have a visit window of 3 days. Study visits from Week 16 through to Week 64 will have a visit window of 7 days.  Subjects will 
not be considered out of compliance if visit windows extend because of events (e.g., holidays, vacations, personal emergencies). However, determination of the maximum visit 
window deviation will be at the discretion of the medical monitor.
2.
Telephone call to occur between study visits at least weekly from Baseline to Week 16 (it is recommended that calls occur every 3-5 days during the first 2 weeks of randomised 
treatment and after Week 6 when the study drug dose is increased), and at Week 22, Week 34, Week 46 and as required to advise subjects on insulin dose adjustments, adverse 
event (AE) monitoring, hypoglycaemia monittoring, and concomitant medication usage.
3.
Visit to be performed once other screening tests indicate eligibility.
4.
See Section 6.3.2.1  for details on the MMTT. Screening MMTT to be performed once other screening test indicate eligibility and at least 28 days from the date of diagnosis of 
T1DM.  Take a urine sample at 120 mins post- MMTT for assessment of urinary C-peptide and urinary creatinine.  Subjects to void their bladders just prior to the start of the 
MMTT.
5.
7 point glucose self-monitoring: before and 2 hours after breakfast, lunch and dinner, at bedtime, on one day in the week prior to each scheduled assessment (to coincide with one 
of the days that the CGM is conducted). 
6.
To be performed in the week prior to the visit. Subject to make an additional visit to the study site to have the CGM monitor fitted/inserted
7.
Perform complete physical examination at Screening and Week 52. Perform brief physical examination at other time points.
8.
Vital signs include weight, blood pressure, and heart rate (pulse). Height to be measured  at Screening only. Calculate body mass index at Screening. 
9.
All 12-lead ECGs to be performed in triplicate (approx 10 mins apart) and before measurement of vital signs and collection of blood samples for laboratory testing. Subjects to be 
semi-recumbent for 10 to 15 minutes before ECGs.
10. Only diabetic ketoacidosis SAEs, hypoglycaemia SAEs and SAEs thought to be related to study procedures need to be reported during Screening
11. See Section 6.4.2 for hypoglycaemia event criteria and reporting requirements.  . Urine ketostix to be performed regularly according to clinical practice (see Section  5.1.2 )
12. Fasting is defined as no food or drink (except water) for at least 8 hours before blood draw.
13. Anti-GAD, anti-IA2, IAA
14. If results are required quickly for eligibility purposes, local labs may be used for the Screening sample only.  If local labs are used, a screening sample must also be sent to the 
central lab. 

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15. Immunogenicity sampling is to be done prior to dosing throughout study
16. Haematology to include complete blood count with haemoglobin, other red blood cell indices, white blood cell count differential, and platelet count.
17. Clinical chemistry to include: glucose, blood urea nitrogen, creatinine, sodium, potassium, chloride, carbon dioxide, calcium, total protein, albumin, total bilirubin, direct bilirubin, 
alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, -glutamyltransferase, uric acid, magnesium, phosphorus.
18. If abnormal at Week 52
19. Urinalysis to include: specific gravity, pH, glucose, protein, blood by dipstick (if warranted, a microscopic evaluation will be completed).
20. Blood sample for pharmacogenetics (PGx) can be collected at any time during the study after the PGx informed consent has been obtained and the subject has been randomly 
assigned to a treatment group.
21. 2ml blood sample. Sample at Week 4 and Week 6 to be taken at least 2 days (48 hours) after the most recent dose of study medication and at any time prior to the next scheduled 
dose.  At Week 6 or any subsequent visit where up or down titration of albiglutide/matching albiglutide placebo coincides with PK sampling, the PK sample must be taken prior to 
titration, such that it is taken no more than 16 hours prior to the subsequent dose.  At Week 8 and Week 16, sample to be collected at least 2 days (48 hours) after a dose but not 
within 4 days of another sample.
22. 8ml blood sample to achieve approx 4 million viable PBMC sample – split into 2 samples
23. 5ml blood sample to achieve approximately 2 ml serum sample – split into 3 samples
24. Pregnancy test for women of child-bearing potential only and at any other time that pregnancy is suspected (U = urine).
25. If hepatitis C antibody positive, RNA polymerase chain reaction should be performed on the same sample to confirm the result.
26. Randomisation to occur at baseline visit.
27. If a subject discontinues study medication, they will be asked to continue to participate in the study and continue to attend study visits where a MMTT is performed. During these 
visits, as well as a MMTT, HbA1c, weight, AEs, hypoglycaemia and insulin usage should be assessed.  Subjects should also continue to complete their diary and must adhere to 
the insulin titration algorithm/guidelines as defined in the protocol through to Week 64. If the subject  refuses to continue attending  these visits after stopping study medication, 
complete this early withdrawal visit.

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Table 4
Time and Events Table –  Telephone Calls
Study 
Procedure
Treatment
(telephone calls to be performed as a minimum at the time points specified (3 days) and as required for 
appropriate management of the subject
Week
11
3
5
7
9
10
11
12
13
14
152
222
342
462
Review glucose monitoring with subject3
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Review the need for insulin dose titration3
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Concurrent medication
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Adverse events
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Assess for hypoglycaemic events4
x
x
x
x
x
x
x
x
x
x
x
x
x
x
1.
Every 3-5 days during the first 2 weeks and for 2 weeks following study drug increase at Week 6
2.
Telephone calls  as necessary from Week 16 through to the end of the study to advise subjects on insulin dose adjustments, adverse event (AE) monitoring, hypoglycaemia and 
diabetic ketoacidosis monitoring
3.
Review the glucose meter readings and adjust basal insulin and meal-time insulin doses as per Table 1 and Table 2, respectively
4.
See Section 6.4.2 for hypoglycaemia event criteria and reporting requirements. Urine ketostix to be performed regularly according to clinical practice

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6.1.
Critical Baseline Assessments
Before any study-specific procedure is performed, valid informed consent must be 
obtained.  
The Baseline visit will take place after information collected during Screening has been 
reviewed and all eligibility criteria have been confirmed.
Critical baseline assessments will include: MMTT (Screening test to be used for 
Baseline), 7 point glucose profile, 72-hour continuous glucose monitoring, insulin usage, 
HbA1c, and body weight.  
Cardiovascular medical history/risk factors will be assessed at baseline.
6.2.
Standard of Diabetic Care
Intensive monitoring and care will be provided according to current standards of care for 
patients with T1DM. Diabetes care will include consultations with a nutritionist or 
dietitian and/or a diabetes educator according to the local institution’s guidelines for 
newly diagnosed T1DM. Study centres are expected to work with each subject to 
optimise glycaemic control, with a target HbA1c level of 7.0 %. Diabetes management 
(insulin therapy, diet, weight maintenance, exercise programmes, etc.) will be directed 
towards helping each subject reach this target or come as close to it as possible. 
Subjects will monitor their plasma glucose levels as described in Section 6.3.2.2.  At each 
visit, study staff will review the use of the plasma glucose monitor and the recent plasma 
glucose data with the subject. Insulin use is discussed in Section 6.3.2.5.
6.3.
Efficacy
6.3.1.
Study Endpoints
6.3.1.1.
Primary Endpoint

Mean change from baseline in stimulated (from MMTT) 2 hour plasma C-peptide 
area under the curve (AUC) at Week 52
6.3.1.2.
Secondary Endpoints

Mean change from baseline in stimulated (from MMTT) 2 hour plasma C-peptide 
AUC  at Week 16, 28 and Week 64

Maximum stimulated plasma C-peptide: the highest value at any time point during 
the 2 hour MMTT after the subject has ingested the mixed meal at Baseline, Week 
16, Week 28, Week 52 and Week 64

Mean change from baseline in plasma glucagon AUC (from MMTT) at Week 16, 28, 
52 and Week 64.

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
Percent of responders (as defined as subjects with HbA1c < 7.0% and insulin dose < 
0.5 units/kg/day) at Weeks 4, 8, 16, 28, 40, 52 and 64

Percent of subjects achieving insulin dose-adjusted haemoglobin A1c (IDAA1C) 
9.0 at Weeks 4, 8, 16, 28, 40, 52 and 64

Change from Baseline in HbA1c at Week 52 and HbA1c over time (i.e., at Weeks 4, 
8, 16, 28, 40, 52 and 64

Change from baseline in mean daily insulin use over the 3 days preceding the visit at 
Weeks 4, 8, 16, 28, 40, 52 and 64. The mean daily insulin use value will be 
calculated in units/kg/day, as the mean of the values of the total amount of insulin 
used per day on each of the 3 consecutive days

Number of events of hypoglycaemia with confirmed self plasma glucose monitoring 
< 3.9 mmol/L and/or requiring 3rd party intervention (i.e., severe, documented 
symptomatic and asymptomatic events see Section 6.4.2) occurring > Week 24 and 
Week 52.

Number and magnitude of hypoglycaemic (<3.9 mmol/L) and hyperglycaemic 
excursions (> 10.0 mmol/L) from the 7 point glucose profile at Baseline, Week 28 
and Week 52

Time spent with a plasma glucose <3.9 mmol/L, between 3.9 and 10.0 mmol/L, and 
>10.0 mmol/L, respectively as performed by 72-hour CGM at Baseline, Week 28 
and Week 52

Change from Baseline in body weight (kg) at Week 52 and Weight over time (i.e., at 
Weeks 2, 4, 6, 8, 16, 28, 40, 52 and 64)

Pharmacokinetic endpoints include the following:

Population estimates of PK parameters (e.g., apparent clearance [CL/F], 
apparent volume of distribution [V/F], first-order absorption rate constant [Ka]), 
associated intersubject variability and residual error 

Covariates and covariate effects on subject PK

Population estimates of PD parameters (e.g., Emax, EC50), associated inter-
subject variability and residual error if permitted by the data
6.3.1.3.
Exploratory Endpoints

Change from baseline in anti-GAD, anti-IA-2 and IAA antibody titres at Week 4, 
Week 16, Week 28, week 40, Week 52 and Week 64

Correlation of urinary C-peptide 120 minute after a mixed meal (urinary creatinine 
corrected) with MMTT C-peptide AUC assessed at Baseline, Week 16, Week 28, 
week 52 and Week 64
Graphical or model-based exploration of PK/PD relationships between albiglutide 
exposure (e.g., steady state AUC) and selected PD endpoints if appropriate and 
permitted by the data

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
Biomarker endpoint: PBMC and serum samples for exploratory biomarker analysis 
will be collected at various timepoints throughout the study (see Table 3).  A 
decision on whether to analyse biomarker samples will be made after review of 
efficacy endpoints at the end of the study. Exploratory biomarkers may include CD8-
positive antigen-specific T-cells and biomarkers for -cell death

Change from baseline in ADDQoL global and domain scores and overview item 
scores at week 52.

-cell function, expressed as an insulin secretion parameter, will be estimated by 
modelling glucose and c-peptide concentrations. The modelling process will include, 
but is not limited to, the deconvolution of c-peptide data in the context of the 
prevailing glucose response to the meal
6.3.2.
Efficacy Assessments
6.3.2.1.
Mixed Meal Tolerance Test
The MMTT will be performed according to the schedule in the Time and Events Table 
(Table 3).  Further details on the procedure are provided in the SPM.
For the 3 days before the MMTT, subjects will be asked to eat a balanced diet consistent 
with advice provided by a nutritionist or dietitian and/or diabetes educator according to 
the local institution’s guidelines for NOT1DM and not to make major changes from their 
customary exercise regimens.
On the evening before the MMTT, subjects should eat a full, usual meal, then fast from 
21:00 h (9 PM) until the MMTT is completed. Water, black coffee, or black tea (with no 
sugar or artificial sweeteners) is allowed during the fast and test.
The MMTT will start in the morning and the time the test is started should be kept as 
consistent as possible. Prior to the test, plasma glucose will be measured using a finger-
stick test and must be > 3.9 mmol/L (70 mg/dL) and 11.1 mmol/L (200 mg/dL) for the 
MMTT to be performed. If the glucose is outside this range, the MMTT must be 
rescheduled.
On the morning of the test, subjects will modify their insulin regimen as follows: 

Withhold the morning dose of long- or intermediate-acting insulin 

No short-acting insulin for at least 6 hours before the test

No rapid-acting insulin for at least 2 hours before the test 
Immediately prior to the test, subjects should void their bladder.
Subjects will consume a standardised amount of a nutritional drink (6 mL per kg body 
weight up to a maximum of 360 mL). The time when the subject starts drinking is 
defined as Time 0. The subject will drink the nutritional drink within 5 minutes or less.
Blood samples will be taken to assess levels of C-peptide, glucose and glucagon at

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
10 minutes before Time 0 (-10 minutes).

Immediately before the subject starts drinking the nutritional drink (Time 0).

15, 30, 60, 90, and 120 minutes after Time 0.
A urine sample will be taken at 120 minutes after Time 0 to assess C-peptide and 
creatinine.
A snack appropriate for a subject with diabetes will be available immediately after the 
120-minute blood draw. As soon as feasible after completing the MMTT, subjects will 
resume their usual insulin and diet regimens.
6.3.2.2.
Self Monitoring of Plasma Glucose
All subjects should be instructed to measure and record plasma glucose values from their 
glucose meter at least 4 times a day at the suggested times for at least 2 consecutive days 
in the week before any study center/telephone contact

Before breakfast

Before lunch

Before dinner

At bedtime
All results of self plasma glucose monitoring will be stored in the subject’s glucose meter 
and communicated to the study site as directed by the investigator. The investigator will 
review the glucose meter readings at the study visit/telephone call and adjust insulin 
doses as per Table 1 and Table 2. If a measurement is only available for 1 day, this will 
be used to assess the need for insulin dose adjustment but the site will need to explain to 
the subject the importance of having at least 2 daily measurements. Additional glucose 
meter monitoring should be performed as per local practice.
Weekly telephone calls (if there is no scheduled study visit) must take place between 
the investigator and subject from Baseline to Week 16, as well as at Week 22, Week 
34, Week 46, and as required until the end of the follow-up phase, in order to 
optimise insulin titration.  It is recommended that the investigator calls the subjects 
every 3-5 days during the first 2 weeks of randomised therapy and after Week 6 
when the study drug dose is increased.
NOTE: the use of a GLP-1R agonist (albiglutide) is expected to decrease the need 
for insulin and, therefore, the investigator will need to ensure careful follow-up of 
each subject accordingly, particularly in the first two weeks after randomisation.
6.3.2.3.
7-Point Self-Monitored Plasma Glucose Profile
A 7 point glucose profile will be conducted at the times specified in the Time and Events 
Table (Table 3). Subjects should be instructed to measure and record plasma glucose 
values from their glucose meter at the following times:

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
Before breakfast (at least 8 hours without food intake)

2 hours after breakfast

Before lunch

2 hours after lunch

Before dinner

2 hours after dinner

At bedtime
6.3.2.4.
72-hour Continuous Glucose Monitoring
Continuous glucose monitoring (CGM) will be conducted at the times specified in the 
Time and Events Table (Table 3).  Three days before the visit, the subject should make an 
additional visit to the study site to have the continuous glucose monitor fitted/inserted.  It 
should be worn for 3 consecutive days and be removed at the scheduled study visit. 
Whilst wearing the CGM, subjects should continue to monitor their plasma glucose as 
described in Section 6.3.2.2 and on one of the days, conduct the 7-point glucose profile as 
described in Section 6.3.2.3.
Subjects and their physicians will not have access to the CGM data during the period of 
monitoring.
6.3.2.5.
Daily Insulin Use
Subjects will record their daily insulin use in a diary. This information will be collected 
for at least 3 days before Baseline, daily for the first 2 weeks and for at least 3 days 
preceding the telephone calls/visits at Week 3 through to Week 16, Week 22, Week 28, 
Week 34, Week 40, Week 46, Week 52 and Week 64. During each of these visits the 
investigator or designee will review the data recorded in the preceding 3 days and if 
errors or gaps are identified (e.g., if the subject did not take insulin and has not entered “0 
units” the investigator will record the missing information from subject recall. Based on 
this information, mean daily insulin use over the 3 consecutive days (in units per kg body 
weight per day) will be calculated for each subject.
6.3.2.6.
HbA1c
HbA1c will be recorded at visits as shown in the Time and Events Table (Table 3).
6.3.2.7.
Body Weight
Body weight should be measured to the nearest 0.1 kg on a standard calibrated scale. 
Subjects should be dressed in light indoor clothes (no coat, jacket, etc) without shoes and 
with a voided bladder. (NB bladder should not be voided before completion of a MMTT). 
The same equipment should be used wherever possible.

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6.3.2.8.
Audit of Diabetes Dependent Quality of Life (ADDQoL)
The ADDQoL is a validated instrument for the assessment of the impact of diabetes on 
quality of life. The original instrument has undergone further development since its 
publication in 1999, and the current version, the ADDQoL 19 will be used in this trial 
([Bradley, 1999; Bradley, 2002; Wee, 2006].  The ADDQoL is designed for use in 
clinical applications, and as an outcome measure in clinical trials evaluating new 
treatments, and was shown to be sensitive to a change in insulin regimen in the DAFNE 
trial [Amiel, 2002].
The ADDQoL consists of two overview items designed for audit purposes: generic 
“present QoL” and diabetes-specific “impact of diabetes on QoL”. A further 18 items 
assess the impact of diabetes on a range of quality of life domains including physical 
functioning, symptoms, psychological well-being, social well-being, role activities and 
personal constructs. Respondents rate both impact of diabetes on applicable domains and 
also the importance of those domains for their QoL. Respondents also indicate if some 
domains are not relevant to them.  The instrument thus yields a weighted global score 
calculated only on domains relevant to the respondent in addition to individual domain 
and overview item scores.
6.4.
Safety
6.4.1.
Safety Endpoints

Hypoglycaemic Events

Incidence of hypoglycaemia (in total and by each category as defined by ADA 
criteria (see Section 6.4.2) overall and in 3 monthly intervals (i.e., from Baseline 
to Week 12, >Week 12 to Week 24, >Week 24 to Week 36, >Week 36 to 
Week 52, >Week 52 to Week 64

Incidence of hypoglycaemia with plasma glucose <3.1 mmol/L (< 56mg/dL) 
regardless of symptoms).

Incidence of daytime hypoglycaemia (in total and by category) (defined as 
hypoglycaemic episodes with an onset between 06:00 h and 00:00 h (inclusive) 
and nocturnal hypoglycaemia (in total and by category) defined as 
hypoglycaemic episodes with an onset between 00:01 h and 05:59 h (inclusive) 
will be determined.  

Incidence of, and number of, hypoglycaemia with plasma glucose <3.9 mmol/l 
(< 70 mg/dL) regardless of symptoms) and/or requiring 3rd party assistance (i.e., 
severe, documented symptomatic and asymptomatic hypoglycaemic events) 
occurring > Week 24 and Week 52 (This is a secondary efficacy endpoint).

Adverse events and serious adverse events

Other adverse events of special interest (AESI) (for example, cardiovascular, 
gastrointestinal, pancreatitis, malignancies (including pancreatic cancer and thyroid 
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atrial fibrillation/flutter, pneumonia, DKA [i.e., ketonuria/ketonaemia, 
hyperglycaemia and acidaemia])

Assessment of clinical laboratory tests (haematology, biochemistry, urinalysis)

Assessment of vital signs measurements, 12-lead ECGs and physical examinations

Immunogenicity (e.g.,percentage of subjects developing anti-albiglutide antibodies 
and characterisation of anti-albiglutide antibodies)
The following sections provide further detail on the safety assessments.  Planned 
timepoints for all safety assessments are listed in the Time and Events Table (Table 3). 
Unscheduled visits will occur as medically necessary.
Liver chemistry stopping and follow-up criteria and AEs are described in Section 6.4.9
and Section 6.4.10 respectively.  
For some AESI, specific eCRF pages will be used to capture additional details about the 
events (e.g., cardiovascular including atrial fibrillation/flutter (Section 6.4.12), injection 
site reactions, pancreatitis, thyroid cancer, pneumonia).
6.4.2.
Subject-Reported Hypoglycaemia Events
Subjects will be asked to report hypoglycaemic events that occur in a diary, which will be 
integrated with the clinical database at the end of the study. These hypoglycaemic events 
that are reported by subjects will be classified as defined by the ADA Workgroup on 
Hypoglycaemia [Seaquist, 2013]. 
Severe Hypoglycaemia

Severe hypoglycaemia 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 Hypoglycaemia

Documented symptomatic hypoglycaemia is an event during which typical 
symptoms of hypoglycaemia are accompanied by a measured plasma glucose 
concentration 70 mg/dL (3.9 mmol/L)
Asymptomatic Hypoglycemia

Asymptomatic hypoglycaemia is an event not accompanied by typical 
symptoms of hypoglycaemia but with a measured plasma glucose concentration 
70 mg/dL (3.9 mmol/L)

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Probable Symptomatic Hypoglycemia

Probable symptomatic hypoglycaemia is an event during which symptoms 
typical of hypoglycaemia are not accompanied by a plasma glucose 
determination but that was presumably caused by a plasma glucose 
concentration 70mg/dL (3.9 mmol/L)
Pseudo Hypoglycemia

Pseudo hypoglycaemia is an event during which the person with diabetes reports 
any of the typical symptoms of hypoglycaemia with a measured plasma glucose 
concentration >70 mg/dL (>3.9 mmol/L) but approaching that level 
Any hypoglycemia event, regardless of intensity, that satisfies the definition of an SAE 
(Section 6.4.10.2) should be categorised as outlined in this section and reported 
appropriately on the SAE eCRF pages. 
6.4.3.
Physical Examination
Either a complete physical examination or brief physical examination will be performed 
at the time points specified in the Time and Events Table (Table 3 ). 
The complete physical examination will include evaluation of the following organ or 
body systems:

Skin (including injection site)

Head, eyes, ears, nose, and throat

Thyroid

Respiratory system

Cardiovascular system

Abdomen (liver, spleen)

Lymph nodes

Central nervous system

Extremities
The brief physical examination will include evaluation of the following organ or body 
systems:

Skin (including injection site)

Respiratory system

Cardiovascular system

Abdomen (liver, spleen)

Central nervous system

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6.4.4.
Height and BMI
Height will be measured at screening only and Body Mass Index (BMI) will be calculated 
(using body weight at Screening) as:
BMI = weight (kg) / [height (m)]2
Note: body weight is detailed under efficacy (Section 6.3.2.7)
6.4.5.
Vital Signs
Assessment of vital signs (blood pressure and pulse rate) will be performed according to 
the schedule in the Time and events Table (Table 3). During visits where ECGs and 
blood samples are taken, the vital sign measurements will be taken after the ECG and 
before the blood draw. 
Vital signs will be taken with the subject either in a semi-recumbent or seated position
after at least a 5-minute rest period.
6.4.6.
Electrocardiograms
12-lead ECG recordings (with subject in semi-recumbent position for 10 to 15 minutes 
before obtaining the ECG) will be performed in triplicate (approximately 10 minutes 
apart) at the time points specified in the Time and Events Table (Table 3). All ECGs will 
be performed before measurement of vital signs and collection of blood samples for 
laboratory testing.
6.4.7.
Clinical Laboratory Assessments
All protocol required laboratory assessments, as defined in Table 3, must be performed 
by the central laboratory, Quest Diagnostics Clinical Laboratory. Note: Screening T1DM 
auto-antibody tests may be carried out at local labs if results are required quickly, 
however a sample is to be sent to the central lab as well. Laboratory assessments must be 
conducted in accordance with the Central Laboratory Manual and Protocol Time and 
Events Schedule. Laboratory requisition forms must be completed and samples must be 
clearly labelled with the subject number, protocol number, site/centre number, and visit 
date. Details for the preparation and shipment of samples will be provided by Quest 
Diagnostics Clinical Laboratory. Reference ranges for all safety parameters will be 
provided to the site by Quest Diagnostics Clinical Laboratory.
If additional non-protocol specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in patient management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), the results must be recorded in the subject’s CRF. Refer to the SPM for 
appropriate processing and handling of samples to avoid duplicate and/or additional 
blood draws.

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Haematology, clinical chemistry, urinalysis, and other laboratory assessments are detailed 
below and will be collected at time points specified in the Time and Events Table 
(Table 3).
During visits when ECGs and vital signs are scheduled, blood samples will be collected 
after the completion of these assessments.
Haematology:

Complete blood count with haemoglobin and other red blood cell indices, white 
blood cell count differential, and platelet count
Clinical Chemistry:

Glucose, blood urea nitrogen, creatinine, sodium, potassium, chloride, carbon 
dioxide, calcium, total protein, albumin, total bilirubin, direct bilirubin, alkaline 
phosphatase, ALT, AST, -glutamyltransferase, uric acid, magnesium, and 
phosphorus
Urinalysis:

Specific gravity, pH, glucose, protein, blood by dipstick (if warranted, a 
microscopic evaluation will be completed)
Other urine tests at time points specified in the Time and Events Table:

Urine pregnancy test (human chorionic gonadotropin [-HCG]) for female 
subjects of child bearing potential

Urinary C-peptide and urinary creatinine as part of the MMTT (see Section 
6.3.2.1) 
Other blood tests at time points specified in the Time and Events Table:

HbA1c

C-peptide, glucose and glucagon as part of the MMTT (see Section 6.3.2.1)

Triglycerides (fasting).  No food or drink [except water] for at least 8 hours 
before sample collection. (Screening only)

T1DM autoantibodies: - anti-GAD, anti-IA2, IAA

Hepatitis B surface antigen (Screening only)

Hepatitis C antibody. If hepatitis C antibody positive, RNA polymerase chain 
reaction should be performed on the same sample to confirm the result
(Screening only)

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6.4.7.1.
Estimated Glomerular Filtration Rate
To ensure appropriate kidney function, eGFR will be calculated at Screening using the 
Modification of Diet in Renal Disease (MDRD) formula [Levey, 2009].
GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if 
African American)
6.4.8.
Immunogenicity Sampling (Anti-albiglutide Antibodies)
Samples for immunogenicity testing will be obtained from all subjects before 
administration of the investigational product at Baseline and according to the schedule 
detailed in the Time and Events Table (Table 3).
The presence of anti-albiglutide antibodies will be assessed using a qualified 
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 neutralising activity. Samples positive for both anti-GLP-1 antibodies and 
drug neutralising antibodies may be tested for GLP-1 neutralising activity.  
Additionally, in the case of systemic allergic reactions that include anaphylaxis, three 1-
mL serum samples should be obtained at a time as close as possible to the event for 
albiglutide-specific IgE testing, and sent to the central laboratory for immediate 
distribution to the contracted testing laboratory (See SPM for details).
Further description of immunogenicity testing is in Appendix 3; instructions for sample 
processing are in the SPM.
6.4.9.
Liver chemistry stopping and follow up criteria
Liver chemistry stopping and follow up criteria have been designed to assure subject 
safety and evaluate liver event etiology (in alignment with the FDA premarketing clinical 
liver safety guidance).  
liver chemistry stopping criteria 1-5 are defined below and are presented in a figure in 
Appendix 2 :
1.
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) (or ALT 3xULN 
and INR>1.5, if INR measured)
NOTE: if serum bilirubin fractionation is not immediately available, withdraw study drug 
for that subject if ALT 3xULN and bilirubin 2xULN. Serum bilirubin fractionation 
should be performed if testing is available. If testing is unavailable, record presence of 
detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and 
suggesting liver injury.
2.
ALT 8xULN.
3.
ALT 5xULN but <8 xULN persists for 2 weeks

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4.
ALT  3xULN if associated with symptoms (new or worsening) believed to be 
related to hepatitis (such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).
5.
ALT 5xULN but <8 xULN and cannot be monitored weekly for 2 weeks
When any of the liver chemistry stopping criteria 1-5 is met, do the following:

Immediately withdraw investigational product for that subject

Report the event to GSK within 24 hours of learning its occurrence

Complete the liver event CRF and SAE data collection tool if the event also meets 
the criteria for an SAE. All events of ALT 3xULN and bilirubin 2xULN (>35% 
direct) (or ALT 3xULN and INR>1.5, if INR measured); INR measurement is not 
required and the threshold value stated will not apply to patients receiving 
anticoagulants), termed ‘Hy’s Law’, must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis). 
NOTE: if serum bilirubin fractionation is not immediately available, withdraw study drug 
for that subject if ALT 3xULN and bilirubin 2xULN. Serum bilirubin fractionation 
should be performed if testing is available. If testing is unavailable, record presence of 
detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and 
suggesting liver injury.

Complete the liver imaging and/or liver biopsy CRFs if these tests are performed

Perform liver event follow up assessments, and monitor the subject until liver 
chemistries resolve, stabilise, or return to baseline values as described below. 

The subject may remain in the study as described in Section 4.4, however, 
investigational product must not be restarted 
In addition, for criterion 1:

Make every reasonable attempt to have subjects return to clinic within 24 hours for 
repeat liver chemistries, liver event follow up assessments (see below), and close 
monitoring

A specialist or hepatology consultation is recommended

Monitor subjects twice weekly until liver chemistries (ALT, AST, alkaline 
phosphatase, bilirubin) resolve, stabilise or return to within baseline values
For criteria 2, 3, 4 and 5:

Make every reasonable attempt to have subjects return to clinic within 24-72 hrs for 
repeat liver chemistries and liver event follow up assessments (see below)

Monitor subjects weekly until liver chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) resolve, stabilise or return to within baseline values; criterion 5 subjects 
should be monitored as frequently as possible.

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Subjects with ALT 5xULN and <8xULN which exhibit a decrease to ALT x3xULN, 
but <5xULN and bilirubin <2xULN without hepatitis symptoms or rash, 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

Can continue investigational product 

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 these subjects meet the liver chemistry stopping criteria, proceed as 
described above

If, after 4 weeks of monitoring, ALT <3xULN and bilirubin <2xULN, monitor 
subjects twice monthly until liver chemistries normalise or return to within baseline 
values. 
For criteria 1-5, make every attempt to carry out the liver event follow up assessments
described below:

Viral hepatitis serology including:

Hepatitis A IgM antibody;

Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM);

Hepatitis C RNA; 

Cytomegalovirus IgM antibody;  

Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing);  

Hepatitis E IgM antibody 

Blood sample for PK analysis, obtained within 3 half-lives (15 days) of last dose. 
Record the date/time of the PK blood sample draw and the date/time of the last dose 
of investigational product prior to blood sample draw on the CRF. 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 SPM. 

Serum creatine phosphokinase (CPK) and lactate dehydrogenase (LDH).

Fractionate bilirubin, if total bilirubin 2xULN.

Obtain complete blood count with differential to assess eosinophilia.

Record the appearance or worsening of clinical symptoms of hepatitis or 
hypersensitivity, such as fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever rash or eosinophilia as relevant on the AE report form.

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
Record use of concomitant medications, acetaminophen, herbal remedies, other over 
the counter medications, or putative hepatotoxins, on the concomitant medications
report form.

Record alcohol use on the liver event alcohol intake case report form.
The following are required for subjects with ALT 3xULN and bilirubin 2xULN (>35% 
direct) but are optional for other abnormal liver chemistries:

Anti-nuclear antibody, anti-smooth muscle antibody, and 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]). 

Only in those with underlying chronic hepatitis B at study entry (identified by 
positive hepatitis B surface antigen):  quantitative hepatitis B DNA and hepatitis 
delta antibody.  NOTE:  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].

Liver imaging (ultrasound, magnetic resonance, or computerised tomography) to 
evaluate liver disease.
6.4.10.
Adverse Events
The investigator or site staff will be responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE.
6.4.10.1.
Definition of an AE
Any untoward medical occurrence in a patient or clinical investigation subject, 
temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product.
Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product.  For marketed medicinal products, this 
also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse.
Events meeting the definition of an AE include:

Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition

New conditions detected or diagnosed after study treatment administration even 
though it may have been present prior to the start of the study

Signs, symptoms, or the clinical sequelae of a suspected interaction

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
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication (overdose per se will not be reported as an 
AE/SAE) unless this is an intentional overdose taken with possible suicidal/self-
harming intent.  This should be reported regardless of sequelae.
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. However, the signs and symptoms and/or clinical sequelae 
resulting from lack of efficacy will be reported if they fulfil the definition of an AE or 
SAE.  
Events that do not meet the definition of an AE include:

Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure is an AE

Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital)

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present 
or detected at the start of the study that do not worsen

The disease/disorder being studied, or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the subject’s 
condition
6.4.10.2.
Definition of an SAE
A serious adverse event is any untoward medical occurrence that, at any dose:
a.
Results in death
b.
Is life-threatening
NOTE:  The term 'life-threatening' in the definition of 'serious' refers to an event in 
which the subject was at risk of death at the time of the event.  It does not refer to an 
event, which hypothetically might have caused death, if it were more severe.
c.
Requires hospitalisation or prolongation of existing hospitalisation
NOTE:  In general, hospitalisation signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or out-patient setting.  Complications that occur during hospitalisation are 
AEs.  If a complication prolongs hospitalisation or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalisation” occurred or was 
necessary, the AE should be considered serious.
Hospitalisation for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE.
d.
Results in disability/incapacity, or
NOTE:  The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions.  This definition is not intended to include experiences 

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of relatively minor medical significance such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
e.
Is a congenital anomaly/birth defect
f.
Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalisation but may jeopardise
the subject or may require medical or surgical intervention to prevent one of the 
other outcomes listed in the above definition.  These should also be considered 
serious.  Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalisation, or development of 
drug dependency or drug abuse.
g.
All events of possible drug-induced liver injury with hyperbilirubinaemia defined as 
ALT 3xULN and bilirubin 2xULN (>35% direct) (or ALT 3xULN and 
INR>1.5, if INR measured) termed ‘Hy’s Law’ events (INR measurement is not 
required and the threshold value stated will not apply to patients receiving 
anticoagulants).
NOTE: bilirubin fractionation is performed if testing is available. If testing is 
unavailable, record presence of detectable urinary bilirubin on dipstick indicating 
direct bilirubin elevations and suggesting liver injury. If testing is unavailable and a 
subject meets the criterion of total bilirubin 2xULN, then the event is still reported 
as an SAE. If INR is obtained, include values on the SAE form. INR elevations >1.5 
suggest severe liver injury.   
6.4.10.3.
Sentinel Events
A Sentinel Event is a GSK-defined SAE that is not necessarily drug-related but has been 
associated historically with adverse reactions for other drugs and is therefore worthy of 
heightened pharmacovigilance. Medical monitor review of all SAEs for possible Sentinel 
Events is mandated at GSK.  The GSK medical monitor may request additional clinical 
information on an urgent basis if a possible Sentinel Event is identified on SAE review. 
The current GSK-defined Sentinel Events are listed below:

Acquired Long QT Syndrome

Agranulocytosis/Severe Neutropaenia 

Anaphylaxis & Anaphylactoid Reactions 

Hepatotoxicity

Acute Renal Failure

Seizure

Stevens Johnson syndrome/Toxic epidermal necrosis

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6.4.11.
Laboratory and Other Safety Assessment Abnormalities 
Reported as AEs and SAEs
Any abnormal laboratory test results (haematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECGs, radiological scans, vital signs measurements), 
including those that worsen from baseline, and felt to be clinically significant in the 
medical and scientific judgement of the investigator are to be recorded as AEs or SAEs.
However, any clinically significant safety assessments that are associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for 
the subject’s condition, are not to be reported as AEs or SAEs.
6.4.12.
Cardiovascular Events
Investigators will be required to fill out event specific data collection tools for the 
following AEs and SAEs:  

Myocardial infarction/unstable angina

Congestive heart failure

Arrhythmias including atrial fibrillation/flutter (see Section 6.4.19).

Valvulopathy

Pulmonary hypertension

Cerebrovascular events/stroke and transient ischemic attack

Peripheral arterial thromboembolism

Deep venous thrombosis/pulmonary embolism

Revascularisation
This information should be recorded in the specific cardiovascular eCRF within one week 
of when the AE/SAE(s) are first reported.
6.4.13.
Death Events
In addition, all deaths will require a specific death data collection tool to be completed.  
The death data collection tool includes questions regarding cardiovascular (including 
sudden cardiac death) and non-cardiovascular death.
This information should be recorded in the specific death eCRF within one week of when 
the death is first reported.
6.4.14.
Injection Site Reactions and Potential Systemic Allergic 
Reactions (e.g., rashes, urticaria, angioedema or anaphylaxis)
Adverse events broadly evaluated as injection site reactions have been reported in 
subjects treated with albiglutide (see IB for further information). . Manifestations were 
generally mild to moderate and included localized rash, itching, redness, or pain in the 

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area of the injection site. In some instances, reactions were noted to become more severe 
with subsequent injections. Injection site reactions should be reported as AEs or SAEs as 
appropriate and additional information on these events will be captured on specific eCRF 
pages. 
Subjects should also be closely monitored for signs of potential allergic or drug 
hypersensitivity reactions including anaphylaxis, angioedema, generalized urticaria, and 
other potential manifestations of systemic allergic or drug hypersensitivity reaction or 
other immune-medicated reactions (e.g., glomerulopathy, vasculitides, and hematologic 
abnormalities). These events should be reported as AEs or SAEs based on the clinical 
evaluation of the subject. The reactions should be followed to completion as typical for 
any AE or SAE.
Subjects with allergic or drug hypersensitivity reactions that are not attributable to 
another cause should have randomized study medication withdrawn and should not be 
rechallenged with albiglutide (see Section 4.4).
In the case of severe systemic allergic reactions that include anaphylaxis, angioedema, or 
other severe potential hypersensitivity reactions, three 1-mL serum samples should be 
obtained for immunogenicity testing and sent to the central laboratory (see details in the 
SPM) for immediate distribution to contracted testing facility for specific immunological 
testing (albiglutide-specific IgE and other antibody tests, as appropriate).
6.4.15.
Pancreatitis
In clinical trials, acute pancreatitis has been reported in association with albiglutide and 
other glucagon-like peptide-1 (GLP-1) receptor agonists.
Subjects must be informed about the symptoms of pancreatitis in the subject information 
and instructed to contact the investigator immediately when they experience these 
symptoms. In the case of suspected pancreatitis, treatment with randomly assigned study 
medication should be withheld, and additional diagnostic measures (clinical examination, 
laboratory parameters, diagnostic imaging) must be initiated per routine clinical practice. 
If the suspected pancreatitis is confirmed, the subject must have investigational product 
stopped and not be rechallenged with study drug.
Detailed information on suspected pancreatitis events will be collected on special pages 
of the eCRF. Cases of suspected pancreatitis will be reviewed by an independent, blinded 
pancreatitis adjudication committee (Section 9.8).
6.4.16.
Pancreatic Cancer
Recently, the FDA and the EMA independently undertook comprehensive evaluations of 
a safety signal arising from postmarketing reports of pancreatitis and pancreatic cancer in 
patients using incretin-based drugs [Egan, 2014]. These investigations, included 
examination of data from a 2013 research report revealing a possible pancreatic safety 
signal [Butler, 2013]. The FDA and EMA concluded that a causal relationship cannot be 
established currently but they will continue to investigate as more data become available.

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As a result, events of pancreatic cancer occurring during the study will be carefully 
evaluated in addition to careful evaluation of malignancies more broadly given the 
interest in potential for malignancies when GLP-1R agonists are used in combination 
with insulin [EMA, 2014]. 
6.4.17.
Medullary Thyroid Cancer
Safety concerns regarding thyroid C cell neoplasia were raised based on long term rodent 
studies with GLP-1R agonists.  If a thyroid nodule is detected at either Screening or 
during the study, this should be evaluated in view of clinical practice guidance documents 
that have recently been published in the United States and Europe [Cooper, 2006; Pacini, 
2006]. For example, the American Thyroid Association Guidelines Taskforce and the 
European Thyroid Cancer Taskforce both recommend that the initial evaluation of a 
thyroid nodule detected by physical examination may include an ultrasound of the neck 
and fine-needle aspiration, as warranted. Additional examinations may also be required 
based on the preliminary findings. The results of any investigation should be recorded in 
the relevant sections of the eCRFs.  If medullary thyroid cancer is diagnosed, study drug 
should be withdrawn.
6.4.18.
Pneumonia
In the Phase III program for albiglutide in T2DM, there was a higher incidence of 
pneumonia events with albiglutide compared with other comparators (refer to the IB for 
further information) and as such, cases of pneumonia occurring during the study will be 
monitored.
Detailed information on pneumonia will be collected on special pages of the eCRF.
6.4.19.
Atrial Fibrillation/Atrial Flutter
In the Phase III program for albiglutide in T2DM, there was a higher incidence of atrial 
fibrillation/atrial flutter events with albiglutide compared with other comparators. These 
events were more common in subjects who were male, older or with renal impairment 
(refer to the IB for further information).  Cases of atrial fibrillation or atrial flutter 
occurring during the study will be monitored.
Detailed information on atrial fibrillation and atrial flutter will be collected on special 
pages of the eCRF (see Section 6.4.12).
6.4.20.
Pregnancy
Any pregnancy that occurs during study participation (i.e., from Baseline through to 
Week 64) must be reported using a clinical trial pregnancy form and investigational 
product withdrawn.  To ensure subject safety, each pregnancy must be reported to GSK 
within 2 weeks of learning of its occurrence.  The pregnancy must be followed up to 
determine outcome (including premature termination) and status of mother and child.  

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Pregnancy complications and elective terminations for medical reasons must be reported 
as an AE or SAE.  Spontaneous abortions must be reported as an SAE.
Any SAE occurring in association with a pregnancy, brought to the investigator’s 
attention after the subject has completed the study and considered by the investigator as 
possibly related to the study treatment, must be promptly reported to GSK.
6.4.21.
Time Period and Frequency of Detecting AEs and SAEs
The investigator, or site staff, is responsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAE.
AEs (with the exception of hypoglycaemia and DKA events) will be collected from the 
start of study treatment and until the follow up contact.  Hypoglycaemia SAEs and DKA 
SAEs will be collected from the time the subject consents until the follow-up contact and 
all other hypoglycaemia events will be collected from Week -2 until the follow-up 
contact.
SAEs (with the exception of hypoglycaemia and DKA SAEs as described above) will be 
collected over the same time period as stated above for AEs. However, any other SAEs 
assessed as related to study participation (e.g., study treatment, protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant 
medication, will be recorded from the time a subject consents to participate in the study 
up to and including any follow up contact. All SAEs will be reported to GSK within 24 
hours, as indicated in Section 6.4.23.
6.4.22.
Method of Detecting AEs and SAEs
Care must 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?”
6.4.23.
Prompt Reporting of Serious Adverse Events and Other Events 
to GSK
SAEs, pregnancies, and liver function abnormalities meeting pre-defined criteria will be 
reported promptly by the investigator to GSK as described in the following table once the 
investigator determines that the event meets the protocol definition for that event.

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Initial Reports
Follow-up Information on a Previous 
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
All SAEs
24 hours
“SAE” data 
collection tool
24 hours
Updated “SAE” 
data collection tool
Cardiovascular or 
death event
Initial and 
follow up 
reports to be 
completed 
within one 
week of when 
the 
cardiovascular 
event or death 
is reported 
“CV events” 
and/or “death” 
data collection 
tool(s) if 
applicable
Initial and follow 
up reports to be 
completed within 
one week of when 
the cardiovascular 
event or death is 
reported
Updated “CV 
events” and/or 
“death” data 
collection tool(s) if 
applicable
Pregnancy
2 weeks
“Pregnancy 
Notification Form”
2 weeks
“Pregnancy Follow-
up Form”
Liver chemistry abnormalities 
ALT3xULN and
Bilirubin2xULN 
(>35% direct) (or 
ALT3xULN and
INR>1.5, if INR 
measured)1
24 hours2
“SAE” data 
collection tool.  
“Liver Event CRF” 
and “Liver 
Imaging” and/or 
“Liver Biopsy” 
CRFs, if 
applicable3
24 hours
Updated “SAE” 
data collection 
tool/“Liver Event” 
Documents3

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Initial Reports
Follow-up Information on a Previous 
Report
Type of Event
Time Frame
Documents
Time Frame
Documents
ALT8xULN; 
ALT3xULN with 
hepatitis or rash or 
3xULN and <5xULN 
that persists4 
weeks
24 hours2
“Liver Event” 
Documents 
(defined above) 3
24 hours
Updated “Liver 
Event” Documents3
ALT5xULN plus 
bilirubin <2xULN
24 hours2
“Liver Event” 
Documents 
(defined above) 
do not need 
completing unless 
elevations persist 
for 2 weeks or 
subject cannot be 
monitored weekly 
for 2 weeks3
24 hours
Updated “Liver 
Event” Documents, 
if applicable3
ALT5xULN and 
bilirubin <2xULN that 
persists 2 weeks
24 hours2
“Liver Event” 
Documents 
(defined above) 3
24 hours
Updated “Liver 
Event” Documents3
ALT3xULN and <5x 
ULN and bilirubin 
<2xULN
24 hours2
“Liver Event” 
Documents 
(defined above) 
do not need 
completing unless 
elevations persist 
for 4 weeks or 
subject cannot be 
monitored weekly 
for 4 weeks3
24 hours
Updated “Liver 
Event” Documents, 
if applicable3
1.
INR measurement is not required; if measured, the threshold value stated will not apply to patients receiving 
anticoagulants.
2.
GSK must be contacted at onset of liver chemistry elevations to discuss subject safety
3.
Liver Event Documents (i.e., “Liver Event CRF” and “Liver Imaging CRF” and/or “Liver Biopsy CRF”, as 
applicable) should be completed as soon as possible.
.
For detailed descriptions of liver chemistry abnormalities, see Section 6.4.9.
The method of recording, evaluating and follow-up of AEs and SAEs plus procedures for 
completing and transmitting SAE reports to GSK are provided in the SPM.  Procedures 
for post-study AEs/SAEs are provided in the SPM.
Procedures for documenting, transmitting and follow-up of medical device incidents 
along with the regulatory reporting requirements for medical devices are provided in the 
SPM.

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6.4.23.1.
Regulatory Reporting Requirements for SAEs
Prompt notification of SAEs by the investigator to GSK is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects 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.
6.5.
Pharmacokinetics
During the Treatment Period, sampling for PK assessments will occur at Visits 5 
(Week 4) and 6 (Week 6); 2 samples will also be collected at any time after Visits 
7 (Week 8) and 8 (Week 16). A total of 4 blood samples (2 mL each) will be obtained 
from each subject. 
The samples collected at Visits 5 (Week 4) and 6 (Week 6) must be taken at least 2 days 
(48 hr) following the most recent dose of albiglutide/albiglutide matching placebo and 
may be taken at any time prior to the next dose. At Visit 6 (Week 6), or any subsequent 
visit where up or down titration of albiglutide/matching albiglutide placebo coincides 
with PK sampling, the PK sample must be taken prior to titration, such that it is taken no 
more than 16 hours prior to the subsequent dose. 
The PK samples drawn at or any time after Visits 7 (Week 8) and 8 (Week 16) must be 
collected at least 2 days (48 hr) after a dose; however, the samples are not to be taken 
within 4 days of another sample.
All PK/PD samples will be processed according to instructions in the SPM and sent to the 
central laboratory for processing. It is critical that the actual sampling dates and times of 
PK sample collections are recorded accurately.
Plasma analysis will be performed under the control of GSK PTS-DMPK/Scinovo, the 
details of which will be included in the SPM. Concentrations of albiglutide will be 
determined in plasma samples using the currently approved bioanalytical methodology. 
Raw data will be archived at the bioanalytical site (detailed in the SPM).
Once the plasma has been analysed for albiglutide any remaining plasma may be 
analysed for other compound-related metabolites and the results reported under a separate 
GSK PTS-DMPK protocol.

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6.6.
Pharmacogenetic Research
Information regarding pharmacogenetic (PGx) research is included in Appendix 1.
6.7.
Biomarker Samples
Blood samples (serum samples and viable peripheral blood mononuclear cells (PBMC)) 
for exploratory biomarkers (see below) associated with autoimmune pathology will be 
collected at the time points indicated in the Time and Event Table (Table 3), frozen and 
stored.
After completion of the clinical trial and/or of any Interim Analysis, investigations may
be performed on samples collected during the course of the trial to detect factors or 
profiles that correlate with other measures of response to treatment with albiglutide or 
with T1DM status. The results gained may also be of application for medically related 
conditions.  Performance of these investigations will be conditional on the results of the 
clinical trial [principally, but not exclusively, on the primary measures of the clinical trial 
outcome] and samples may be selected for analysis on the basis of the clinical outcome.
Comparative examination of pre-dosing profiles of participants may uncover known or 
novel candidate biomarkers/profiles which could be used to predict response to treatment 
with albiglutide or provide new insights into T1DM and medically related conditions.  
Comparative examination of post-dosing profiles in conjunction with pre-dosing profiles 
may yield known and novel candidate biomarkers/profiles and new insights which relate 
to the action of albiglutide.
Exploratory biomarkers may include CD8-positive antigen-specific T-cells and 
biomarkers for -cell death. If stored PBMCs are tested for CD8, samples will first be 
tested to see if they are HLA-A2 positive. The assay for -cell death is based on DNA 
sequencing. As both of these assays require genetic testing, subjects will be asked to 
provide consent to give these samples.  Refusing consent for these samples, will not 
prevent the subject from participating in the rest of the study. 
Full details on sample collection, processing and shipment will be provided in the 
SPM/Quest manual.
All samples will be retained for a maximum of 15 years after the last subject completes 
the trial.
7.
DATA MANAGEMENT
For this study subject data will be entered into GSK defined electronic case report forms 
(eCRFs), transmitted electronically to GSK or designee and combined with data provided 
from other sources in a validated data system.  
Management of clinical data will be performed in accordance with applicable GSK 
standards and data cleaning procedures to ensure the integrity of the data, e.g., removing 
errors and inconsistencies in the data.  Adverse events and concomitant medications 

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terms will be coded using MedDRA and an internal validated medication dictionary, 
GSKDrug.  In all cases, subject initials will not be collected or transmitted to GSK 
according to GSK policy.
8.
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS
8.1.
Hypotheses
For this Phase II, randomised, multicentre, double blind, placebo controlled study, the 
primary objective is to evaluate the efficacy of albiglutide versus placebo on endogenous 
insulin secretion. The primary efficacy analysis endpoint will be change from baseline 
stimulated 2 hour MMTT C-peptide AUC at Week 52 following one year of treatment. 
Specifically, the treatment effect will be evaluated using the least squares means contrast 
relative to placebo. This contrast will be evaluated inferentially with a 2-sided t-test at the 
0.05 criterion significance level.
8.2.
Study Design Considerations
8.2.1.
Sample Size Assumptions
The study will randomly assign approximately 68 subjects to albiglutide+insulin group or 
placebo+insulin group in a 3:1 ratio, and allow for a 10% drop-out rate. Power is 
calculated for the primary efficacy analysis, comparing the change from baseline in 
stimulated 2 hour MMTT plasma C-peptide AUC (nmol/L) between albiglutide and 
placebo at 52 weeks.
Assumptions used in the power calculation are based upon results from the DEFEND-1
study [GlaxoSmithKline Document Number; 2011N125757_00]. 

In the DEFEND-1 study, 91 subjects with a diagnosis of new-onset type 1 diabetes 
mellitus, aged 12-45 years, were enrolled to placebo+insulin group with similar 
inclusion/exclusion criteria and treated for 52 weeks.  Among these placebo subjects, 
53 of them were aged 18-30 years. The stimulated 2-hour MMTT C-peptide AUC 
change from baseline at Week 52 was -0.27 nmol/L. The corresponding observed 
standard deviation (SD) was 0.31 nmol/L. It is assumed that the SDs of 2 hour 
MMTT C-peptide AUC for the albiglutide and placebo groups in this study will be 
similar to the SD of the placebo group in DEFEND-1. 

As a conservative simplifying assumption, baseline was not included as a covariate. 
This is likely a less efficient analysis than if baseline was included as a covariate, 
and so the power estimate should be conservative.
With historical data from 53 placebo subjects in the DEFEND-1 study, a Bayesian 
approach will used for power and minimal detective treatment difference evaluation.  
Depending on the degree to which historical data will contribute to the placebo result of 
the current trial, at a two-sided significance level of 0.05, a sample size of 60 evaluable 
subjects (45 in the albiglutide group and 15 in the placebo group) provides 90% power to 
detect a treatment effect in the current study in the range from 0.19 nmol/L (using all the 

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information from the 53 placebo subjects from the DEFEND-1 study) to 0.30 nmol/L (not 
using any historical data).  The corresponding minimal detectable difference will be 0.12 
nmol/L to 0.18 nmol/L
8.2.2.
Sample Size Sensitivity
Table 5 presents the study power for a combination of magnitudes of treatment effect size 
(rows) and various weight of historical data(%) (columns) and their contribution to the 
current placebo group. Table 6 presents the minimal detective difference under various 
weight of historical data. The greater the weight given to placebo data from the 
DEFEND-1 study, the greater the placebo effect from DEFEND-1 study will influence 
the placebo effect of the current study.  Given that there are more placebo subjects in the 
DEFEND-1 study compared to the current study of 15 evaluable subjects, it is reasonable 
to assume DEFEND-1 placebo data contributes 50% of its placebo information. 
Sensitivity analyses will be done with low and high contribution rates.
Table 5
Power for DEFEND-1 in a 1-Sided 2-Sample t Test at the 0.05 Level
True 
Treatment 
Difference, 
(nmol/L)
Power (%) at a Sample Size of 60 With 3:1 Randomisation
Weight  of historical placebo data
0
30%
50%
70%
100%
0.20
58%
78%
85%
89%
92%
0.22
66%
86%
91%
94%
96%
0.30
90%
99%
99%
100%
100%
Table 6
Minimal Detectable Difference
Sample Size of 60 With 3:1 Randomisation
Weight  of historical placebo data
0
30%
50%
70%
100%
Minimal 
Detectable 
Difference
(nmol/L)
0.18
0.14
0.13
0.12
0.12
8.2.3.
Sample Size Re-estimation
No sample size re-estimation is planned for this study.

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8.3.
Data Analysis Considerations
8.3.1.
Analysis Populations
The intent-to-treat (ITT) population will include all randomly assigned subjects who
receive at least 1 dose of study medication and who have at least 1 post-baseline 
assessment of the primary endpoint. ITT subjects will be analysed according to 
randomised treatment.
The safety population will include all enrolled subjects who receive at least 1 dose of 
study treatment. The safety population subjects will be analysed according to the 
treatment received.
Other analysis populations will be defined in the Reporting Analysis Plan (RAP).
8.3.2.
Analysis Data Sets
Not applicable.
8.3.3.
Treatment Comparisons
8.3.3.1.
Primary Comparisons of Interest
The primary comparison of interest is to demonstrate that the change from baseline in 2-
hour MMTT plasma C-peptide AUC at Week 52 in the albiglutide group is significantly 
different from the placebo group. The hypothesis will be tested at the 5% significance 
level using a two-sided test. The primary comparison will be conducted using the ITT 
population.
8.3.3.2.
Other Comparisons of Interest
The secondary and exploratory efficacy endpoints , and the safety endpoints will be 
compared between treatment groups as specified in the study objective sections. In 
general, comparisons of efficacy endpoints will use the ITT population and comparisons 
of safety endpoints will use the safety population as defined in Section 8.3.1.
8.3.4.
Interim Analysis
No formal interim analyses are planned.
8.3.5.
Key Elements of Analysis Plan
8.3.5.1.
General Statistical Methods
Descriptive statistics will be presented for safety and efficacy endpoints. For continuous 
variables, descriptive statistics will include the mean, median, standard deviation, 
minimum, maximum, number of available observations, and number of missing 

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observations. For ordinal and nominal variables, descriptive statistics will include 
numbers and percentages for each score or category, number of available observations, 
and number of missing observations. Discrete numeric variables (counts) will be 
described through frequency counts (grouping counts as needed for clarity), mean, 
median, variance, minimum, maximum, number of available observations, and number of 
missing observations. Descriptive statistics will be provided for each treatment group. 
Complete data listings will be provided. Graphical displays will be presented when they 
add to understanding of the data.
Unless explicitly stated otherwise, results of hypothesis tests will be considered 
statistically significant if p values are less than or equal to 0.05, and will be deemed not 
significant if p values are greater than 0.05.
Statistical analyses will be performed with SAS, Version 9.1 or later, and R, Version 
2.5.0 or later.
8.3.5.2.
Subject Disposition and Demographic and Baseline Characteristics
Subject disposition, subject demographic and baseline characteristics will be summarised 
by treatment group and for both groups combined. Additional tabulations may be 
produced for various subgroups of subjects. Disposition, demographic characteristics, and 
other baseline characteristics will be listed by subject.
8.3.5.3.
Efficacy Analyses
8.3.5.3.1.
Primary Efficacy Analysis
The primary efficacy endpoint is change from baseline in 2 hour MMTT plasma 
C-peptide AUC at Week 52. The primary comparison is between this value in the 
albiglutide group and the placebo group, adjusting for baseline 2 hour MMTT plasma 
C-peptide AUC and age. 
A mixed-effects model for change from baseline in 2 hour MMTT C-peptide AUC will 
be used to estimate and compare the albiglutide and placebo treatment effects at Week 
52. Specifically, a repeated-measures mixed-effects model will be fitted with change 
from baseline 2 hour MMTT plasma C-peptide AUC as a dependant variable and
baseline 2 hour MMTT C-peptide AUC, age group, treatment group, visit, and treatment 
group-by-visit interaction as independent variables. Historical placebo information with 
50% weight will be incorporated into the mixed effect model by Baysian modelling using 
SAS PROC MCMC procedure. The mixed effects model will use a general (unstructured) 
covariance matrix as specification for the covariance among observations from the same 
subject. 
A test of the treatment group difference at Week 52 will be provided by the comparison 
of the appropriate treatment group*visit least square means (Least square means). 

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The difference will be considered significant if the two-sided p-value for the comparison 
between treatments in change from baseline 2 hour MMTT C-peptide AUC is less than or 
equal to 0.05. The corresponding 95% confidence intervals will also be presented.
Subjects are scheduled to have on-therapy MMTTs performed at Week 16, 28, 52. Using 
a longitudinal repeated-measures model will provide an unbiased treatment difference 
estimate for the Week 52 time point, with better precision achieved by accounting for 
intra-subject variability than an analysis of covariance approach. In the event of missing 
observations at Week 52, the planned analysis and test are valid under a “missing at 
random (MAR)” assumption where missing data may depend on prior observations.
The above repeated mixed-effects model analysis will be repeated without placebo 
information from DEFEND1, and with 100% placebo information from the DEFEND 1 
study as sensitivity analyses.
In addition to the t-tests described above, there will be a test for treatment group-by-time 
(continuous) interaction in the model (adjusted for baseline value and randomisation 
strata). A significant interaction would indicate that the treatment difference in 2 hour 
MMTT C-peptide AUC between groups varies over time to a greater degree than 
expected by chance. If there is no evidence of an interaction at the 0.05 level of 
significance, then the overall treatment group LS means (across all time points) will be 
reported.
Summary statistics for 2 hour MMTT C-peptide AUC and change from baseline will be 
tabulated by treatment group and assessment time for Week 16, 28, 52 and 64. Mean 
C-peptide AUC and mean change from baseline in C-peptide AUC will be plotted over 
time by treatment group.
An additional analysis of interest will be to examine the C-peptide AUC data for a trend 
over time. To assess this, a mixed-effects model will be specified with a linear trend after 
Week 28 to describe the mean rate of change (decrease) within treatment groups over 
time. To allow for an acute effect on C-peptide as observed in other studies, the baseline 
value will be entered as a covariate (not as one of the repeated measures over time); time 
will then be rescaled such that Time 0 is the first post-treatment C-peptide value, i.e., that 
at Week 16. The mixed-effects model will be specified with baseline C-peptide AUC, 
treatment group, and age as fixed effects. Between-subject differences in change from 
baseline AUC and treatment effect over time will be handled by specification of random 
effects for intercept and slope (time), respectively. The treatment group fixed effect will 
test the difference between groups in the mean intercepts (means at Week 16), and the 
treatment group-by-time interaction effect will test for differences between slopes over 
the period from Week 28 through Week 52. A general (unstructured) covariance matrix 
will be specified for the covariance among observations from the same subject.

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8.3.5.3.2.
Secondary Efficacy Analyses
Responder Analysis
The proportions of subjects meeting the definition of a responder will be compared 
between the albiglutide group and the placebo group at Week 4, Week 16, week 28, 
Week 52 and Week 64. A subject will be considered a responder if, at a given visit, the 
subject has: 

HbA1c ≤ 7.0% and

Mean daily insulin use < 0.5 units/kg/day.
The proportion of responders will be analysed using descriptive statistics (frequency and 
percentage) by treatment group, and treatment comparisons will be undertaken with non-
parametric, covariance-adjusted, extended Mantel-Haenszel tests .This technique is 
especially suited for situations in which covariance adjustment is needed to optimise 
statistical power, while minimising the modeling assumptions.
Percent of Subjects Achieving Partial Remission Status.
A subject achieving partial remission status is defined as a subject with Insulin Adjusted 
A1c ( IDAA1C) 9  [Mortensen, 2009]. This secondary endpoint will be analysed in a 
similar method to the Responder analysis.
HbA1c.
This secondary efficacy analysis is to determine whether mean HbA1c (adjusted for 
baseline HbA1c, and age) is reduced in the albiglutide group compared to the placebo 
group at Week 4, Week 16, Week 28, Week 52 and Week 64.
HbA1c change from baseline will be analysed similarly to maximum stimulated plasma 
C-peptide using a mixed-effects model. 95% confidence intervals and the p-value for the 
treatment group differences at each time point of interest will be presented.
Exogenous Insulin Use.
This secondary efficacy analysis is to determine whether change in mean daily insulin 
use (adjusted for baseline daily insulin use and age) is reduced in the albiglutide group 
compared to the placebo group, at Week 4, Week 16, Week 28, Week 52 and Week 64. 
In this section, the term “mean daily insulin use” will refer to mean total daily insulin 
dose per kg body weight, which will be computed for each subject as the average of the 
total recorded daily insulin intake for at least three days, divided by the subject’s body 
weight in kg, using the most recently obtained weight measurement.
A similar mixed-effects model to that utilised for the maximum stimulated plasma C-
peptide will be used to calculate the effects of albiglutide and placebo treatment on 
change from baseline mean daily insulin use.

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The treatment group differences and 95% confidence intervals from repeated mixed-
effects model at each time point of interest will be presented.  
Subject-Reported Hypoglycaemic Events
Incidence of severe hypoglycaemia, documented symptomatic hypoglycaemia, and 
asymptomatic hypoglycaemia (as defined in Section 6.4.2) will be tabulated by treatment 
group. Incidence is defined as the numbers of subject-reported hypoglycaemic events per 
subject, and total percentages of subjects affected.
7- point glucose profile
Glucose level at each point will be summarised by treatment group at Baseline, Week 28 
and Week 52.  Number and magnitude of hypoglycaemic (<3.9 mmol/L) and 
hyperglycaemic excursions (> 10.0 mmol/L) from the 7-point glucose profile will also be 
reported at Baseline, Week 28 and Week 52.
72-hour CGM
Time spent with a plasma glucose <3.9 mmol/L, between 3.9 and 10.0 mmol/L, and 
>10.0 mmol/L will be summarised by treatment group at Baseline, Week 28 and Week 
52.
8.3.5.3.3.
Exploratory Analyses
Correlation between 120 minutes urinary C-peptide AUC and MMTT C-peptide 
AUC
Descriptive statistics for change from baseline in 120 minutes urinary C-peptide 
(corrected for urinary creatinine) AUC will be presented by treatment group and 
assessment time at Week16, Week 28, Week 52 and Week 64. The scatter plots of 
individual values of change in urine C-peptide AUC versus MITT C-peptide AUC will be 
presented for each treatment group and for both groups combined for Baseline, Week16, 
Week 28, Week 52 and Week 64.
Other Exploratory Endpoints
CD8-positive antigen specific T-cell responsiveness, and change from baseline in anti-
GAD, anti-IA-2 and IAA antibody titres will be summarized at Week 4, Week 16, Week 
28, Week 40, Week 52 and Week 64.
Change from baseline in global and domain scores in ADDQoL at 52 weeks will be 
compared between the albiglutide and placebo groups, between responders and non-
responders and between subjects achieving partial remission status and subjects not 
achieving partial remission.
A model will be used to derive insulin secretion rates over the time course of glucose 
measurements by deconvolution of the observed C-peptide measurements associated with 
the prevailing glucose levels. Assessments will be made at Weeks -2 (baseline), 16, 28, 
52 and 64. Changes from baseline between the albiglutide and placebo groups will be 

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compared, and also between responders and non-responders and between subjects 
achieving partial remission status and subjects not achieving partial remission.
The details of any further planned analyses will be provided in the RAP.
8.3.5.4.
Safety Analyses
Subject demographics, medical history, prior and concomitant medications, vital sign 
measurements, laboratory values, ECG readings, physical examination assessments, and 
AE rates will be summarised by treatment group using descriptive statistics. For 
continuous variables, these summaries will include sample size, mean, median, standard 
deviation, minimum, and maximum. For categorical variables, the summaries will 
include frequencies and corresponding percentages. No inferential hypothesis testing will 
be performed on the safety variables. Some graphical summaries may be provided as 
well.
Adverse events will be coded using MedDRA. The coded events will be summarised by 
treatment group, in subsets of all treatment-emergent AEs, and all treatment-related AEs. 
Treatment-emergent AEs will be defined as any AEs, regardless of relationship to the 
investigational product, that occur after the first dose of the investigational product. 
Treatment-related AEs will be defined as any AEs that are considered by the investigator 
to be possibly, probably, or definitely related to the investigational product. In addition,
the AE will be considered treatment related if relationship information is missing. 
Listings for the subsets of SAEs and treatment-related SAEs will be provided.
The number and percentage of subjects reporting specific events, such as nausea and 
vomiting, at each study week will be presented. Data for each week will include those 
subjects whose events started during that particular week, and also those with unresolved 
events from previous weeks. The incidence of specific events, such as nausea and 
vomiting, will also be plotted over time.
Further analysis details will be in the RAP.
8.3.5.5.
Immunogenicity analyses
Anti-albiglutide antibody results will be analysed by treatment and by visit. The 
frequency of subjects positive for albiglutide-binding antibody and albiglutide-
neutralising antibody, as well as those positive for GLP-1 and/or albumin cross-reacting 
antibodies, will be provided. Antibody titres for anti-drug antibody and Nab assays will 
be analysed by treatment and dose. Further exploratory analysis may be conducted 
dependent on the antibody response.
8.3.5.6.
Pharmacokinetic Analyses
Albiglutide plasma concentrations and population PK parameters (e.g., CL/F, V/F, and 
Ka) will be summarised for the albiglutide group. The relationship between albiglutide 
PK parameters and patient covariates of interest will be evaluated graphically and in the 
population PK model.

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8.3.5.7.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between plasma albiglutide concentrations and measures of glycaemic 
control (e.g., C-peptide, insulin use, HbA1c, etc) in the subject population will be 
explored, as data permit. The relationship between plasma albiglutide concentrations and 
other potential efficacy, tolerability (e.g., nausea and vomiting), and safety endpoints will 
be explored, as data permit.
8.3.5.8.
Pharmacogenetic Analyses
See Appendix 1 for details about the Pharmacogenetics Analysis Plan.
8.3.5.9.
Missing Data
Laboratory values below the level of quantification (BLQ) will be set to one-half the limit 
of quantification (unless noted otherwise) in computations for the aggregate analyses, but 
will be noted as BLQ in the listings. Laboratory values that are missing will be excluded 
from computations for the aggregate analyses and will be noted as missing in listings. On 
graphs, missing values will be shown by the absence of a data point. 
The MMTT is expected to include assessments of C-peptide, glucose and glucagon at -
10, 0, 15, 30, 60, 90, and 120 minutes, and AUCs are expected to be based on the 
assessments from Time 0 through 120 minutes. If one or more of these assessments is 
missing (note: values reported as BLQ are not considered missing), AUCs will be 
calculated based on the non-missing data using the trapezoidal rule. If the Time 0 
assessment is missing, it will be substituted with the value from the -10 minute time 
point. For an AUC to be calculated, there must be a minimum of one fasting data point 
(assessments scheduled for -10 minutes and Time 0), and one post-mixed meal data point 
(assessments scheduled for 15, 30, 60, 90, and 120 minutes). If this minimum number of 
data points is not available, the AUC will be recorded as missing.  If the MMTT is 
conducted when the plasma glucose values are out of the range specified, the data will 
not be included in the analysis and treated as missing.
The primary efficacy analysis employs a repeated-measures model using all follow-up 
values for all subjects (as described in Section 8.3.5.3.1). Under an MAR assumption 
where the missing data may depend on the prior observations, i.e., the conditional 
independence assumption, the model provides unbiased LSmean estimates for the 
treatment groups at the assessment time points.
If the amount of missing data is large, the potential impact of missing follow-up data on 
the conclusions of the primary analysis will be investigated through sensitivity analyses. 
For example, for each treatment group, the baseline characteristics of the subjects whose 
Week 52 mixed meal-stimulated C-peptide AUC is missing will be compared with those 
subjects with available Week 52 mixed meal-stimulated C-peptide AUC data to provide 
an assessment of the potential for the missing data to cause bias in the conclusions. The 
report will include presentation of the results of the sensitivity analysis, and a discussion 
of the implications of both the sensitivity analysis and the comparisons of baseline 
characteristics on interpreting the conclusions from the primary hypothesis test.

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In analyses of HbA1c and insulin usage, missing data at key analysis time points will be 
imputed using the last observation carried forward method.
8.3.5.10.
Laboratory Values Below Limits of Quantification and Repeat Testing
Laboratory values below the level of quantification (BLQ) will be set to one-half the limit 
of quantification (unless noted otherwise) in computations for the aggregate analyses, but 
will be listed as BLQ in the listings.
If a laboratory test is repeated because of an apparent error, the repeat test result will be 
used in place of the original test result. Both the original test result and the repeat test 
result will be shown in the listings.
9.
STUDY CONDUCT CONSIDERATIONS
9.1.
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrolment of subjects begins.
9.2.
Regulatory and Ethical Considerations, Including the 
Informed Consent Process
Prior to initiation of a study site, GSK will obtain favourable opinion/approval from the 
appropriate regulatory agency to conduct the study in accordance with ICH Good Clinical 
Practice (GCP) and applicable country-specific regulatory requirements.
The study will be conducted in accordance with all applicable regulatory requirements.
The study will be conducted in accordance with ICH GCP, all applicable subject privacy 
requirements, and the ethical principles that are outlined in the Declaration of Helsinki 
2008, including, but not limited to:
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) review and 
favourable opinion/approval of study protocol and any subsequent amendments.
Subject informed consent.
Investigator reporting requirements.
GSK will provide full details of the above procedures, either verbally, in writing, or both.
Before undergoing any Screening procedures, each subject will undergo the process of 
being fully informed about the study procedures and all associated risks and will then 
provide written and dated informed consent according to the regulatory and legal 
requirements of the participating country. The informed consent form must be approved 
by the IEC before it is given to any potential subject.

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Written informed consent must be obtained from each subject prior to participation in the 
study.
In approving the clinical protocol the IEC/IRB and, where required, the applicable 
regulatory agency are also approving the optional assessments e.g., PGx assessments 
described in Appendix 1, unless otherwise indicated.  Where permitted by regulatory 
authorities, approval of the optional assessments can occur after approval is obtained for 
the rest of the study.  If so, then the written approval will clearly indicate approval of the 
optional assessments is being deferred and the study, except for the optional assessments, 
can be initiated. When the optional assessments are not approved, then the approval for 
the rest of the study will clearly indicate this and therefore, the optional assessments will 
not be conducted.
9.3.
Quality Control (Study Monitoring)
In accordance with applicable regulations, 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 include 
identification, agreement and documentation of data items for which the CRF will serve 
as the source document.
GSK will monitor the study to ensure 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.
9.4.
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.
9.5.
Study and Site Closure
The end of the study will be defined as when the last subject has their last visit.

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Upon completion or termination of the study, the GSK monitor will conduct site closure 
activities with the investigator or site staff (as appropriate), in accordance with applicable 
regulations, GCP, and GSK Standard Operating Procedures.
GSK reserves the right to temporarily suspend or terminate the study at any time for 
reasons including (but not limited to) safety issues, ethical issues, or severe non-
compliance.  If GSK determines that such action is required, GSK will discuss the 
reasons for taking such action with the investigator or head of the medical institution 
(where applicable).  When feasible, GSK will provide advance notice to the investigator 
or head of the medical institution of the impending action.
If a study is suspended or terminated for safety reasons, GSK will promptly inform all 
investigators, heads of the medical institutions (where applicable),and/or institutions 
conducting the study.  GSK will also promptly inform the relevant regulatory authorities 
of the suspension/termination along with the reasons for such action.  Where required by 
applicable regulations, the investigator or head of the medical institution must inform the 
IRB/IEC promptly and provide the reason(s) for the suspension/termination.
9.6.
Records Retention
Following closure of the study, the investigator or 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 easily accessible 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 the 
records may be maintained in a format other than hard copy (e.g., microfiche, scanned,
electronic); however, caution must 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.  In addition, they must meet accessibility and retrieval standards, 
including regeneration of a hard copy, if required.  The investigator must also ensure that 
an acceptable back-up of the reproductions exists and that there is an acceptable quality 
control procedure in place for creating the reproductions.
GSK will inform the investigator of the time period for retaining the site records in order 
to comply with all applicable regulatory requirements.  The minimum retention time will 
meet the strictest standard applicable to a particular site, as dictated by local 
laws/regulations, GSK standard operating procedures, and/or institutional requirements.
The investigator must notify GSK of any changes in the archival arrangements, including, 
but not limited to archival of records at an off-site facility or transfer of ownership of the 
records in the event that the investigator is no longer associated with the site.

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9.7.
Provision of Study Results to Investigators, Posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location.
GSK will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as
appropriate.
GSK will provide the investigator with the randomisation codes for their site only after 
completion of the full statistical analysis.
The results summary will be posted to the Clinical Study Register no later than eight 
months after the final primary completion date, the date that the final subject was 
examined or received an intervention for the purposes of final collection of data for the 
primary outcome.  In addition, a manuscript will be submitted to a peer reviewed journal 
for publication no later than 18 months after the last subject’s last visit (LSLV).  When 
manuscript publication in a peer reviewed journal is not feasible, a statement will be 
added to the register to explain the reason for not publishing.
9.8.
Pancreatitis Adjudication Committee
The pancreatitis adjudication committee composed of independent specialists in 
gastroenterology will review cases of possible pancreatitis. Details of this committee and 
case adjudication will be described a separate charter.

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Tsai EB, Sherry NA, Palmer JP, Herold KC. The rise and fall of insulin secretion in type 
1 diabetes mellitus. Diabetologia. 2006;49:261-267. 
Van Belle TL, Coppieters KT, Von Herrath MG. Type 1 diabetes: Etiology, immunology 
and therapeutic strategies. Physiol rev. 2011;91:79-118. 
Wee HL. Usefulness of the Audit of Diabetes-Dependent Quality of Life (ADDQoL) 
Questionnaire in Patients with Diabetes in a Multi-Ethnic Asian country. 
Pharmacoeconomics. 2006;24(7):673-682. 
Xue S, Wasserfall C, Parker M et al. Exendin-4 treatment of non-obese diabetic mice 
increases beta-cell proliferation and fractional insulin reactive area. J Diabetes 
Complication. 2010;24(3):163-7. 
Xue S, Wasserfall CH, Parker M et al. Exendin-4 therapy in NOD mice with new onset 
diabetes increases regulatory T cell frequency. Ann N Y Acad Sci. 2008;1150 (Dec):152-
6. 

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11.
APPENDICES
11.1.
Appendix 1: Pharmacogenetic Research
Pharmacogenetics – Background
Pharmacogenetics (PGx) is the study of variability in drug response due to hereditary 
factors in populations.  There is increasing evidence that an individual's genetic 
background (i.e., genotype) may impact the pharmacokinetics (absorption, distribution, 
metabolism, elimination), pharmacodynamics (relationship between concentrations and 
pharmacologic effects or the time course of pharmacologic effects) and/or clinical 
outcome (in terms of efficacy and/or safety and tolerability).  Some reported examples of 
PGx associations with safety/adverse events include:
Drug
Disease
Gene 
Variant
Outcome
Abacavir
HIV 
[Hetherington, 
2002; 
Mallal, 2002; 
Mallal, 2008]
HLA-B* 
57:01 
(Human 
Leukocyte 
Antigen B)
Carriage of the HLA-B*57:01 variant has been 
shown to increase a patient's risk for 
experiencing hypersensitivity to abacavir.  
Prospective HLA-B*57:01 screening and 
exclusion of HLA-B*57:01 positive patients 
from abacavir treatment significantly 
decreased the incidence of abacavir 
hypersensitivity.  Treatment guidelines and 
abacavir product labeling in the United States 
and Europe now recommend (US) or require 
(EU) prospective HLA-B*57:01 screening prior 
to initiation of abacavir to reduce the incidence 
of abacavir hypersensitivity.  HLA-B*57:01
screening should supplement but must never 
replace clinical risk management strategies for 
abacavir hypersensitivity.
Carbamazepine
Seizure, 
Bipolar 
disorders & 
Analgesia 
[Chung, 2010; 
Ferrell, 2008]
HLA-
B*15:02
Independent studies indicated that patients of 
East Asian ancestry who carry HLA-B*15:02
are at higher risk of Stevens-Johnson 
Syndrome and toxic epidermal necrolysis.  
Regulators, including the US FDA and the 
Taiwanese TFDA, have updated the 
carbamazepine drug label to indicate that 
patients with ancestry in genetically at risk 
populations should be screened for the 
presence of HLA-B*15:02 prior to initiating 
treatment with carbamazepine.

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Drug
Disease
Gene 
Variant
Outcome
Irinotecan
Cancer 
[Innocenti, 
2004; Liu, 
2008; Schulz, 
2009]
UGT1A1*28
Variations in the UGT1A1 gene can influence 
a patient’s ability to break down irinotecan, 
which can lead to increased blood levels of 
the drug and a higher risk of side effects. A 
dose of irinotecan that is safe for one patient 
with a particular UGT1A1 gene variation might 
be too high for another patient without this 
variation, raising the risk of certain side-effects 
that include neutropenia following initiation of 
Irinotecan treatment.  The irinotecan drug 
label indicates that individuals who have two 
copies of the UGT1A1*28 variant are at 
increased risk of neutropenia.  A genetic blood 
test is available that can detect variations in 
the gene.    
A key component to successful PGx research is the collection of samples during the 
conduct of clinical studies.
Collection of whole blood samples, even when no a priori hypothesis has been identified, 
may enable PGx analysis to be conducted if at any time it appears that there is a potential 
unexpected or unexplained variation in response to albiglutide.
Pharmacogenetic Research Objectives
The objective of the PGx research (if there is a potential unexpected or unexplained 
variation) is to investigate a relationship between genetic factors and response to 
albiglutide.  If at any time it appears there is potential variability in response to 
albiglutide in this clinical study or in a series of clinical studies with albiglutide, the 
following objectives may be investigated – the relationship between genetic variants and 
study treatment with respect to:

Safety and/or tolerability 

Efficacy
Study Population
Any subject who is enrolled in the clinical study, can participate in PGx research.  Any 
subject who has received an allogeneic bone marrow transplant must be excluded from 
the PGx research.
Subject participation in the PGx research is voluntary and refusal to participate will not 
indicate withdrawal from the clinical study or result in any penalty or loss of benefits to 
which the subject would otherwise be entitled.

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Study Assessments and Procedures
Blood or saliva samples can be taken for Deoxyribonucleic acid (DNA) extraction and 
used in PGx assessments.
If taking blood samples: in addition to any blood samples taken for the clinical study, a 
whole blood sample (~6 ml) will be collected for the PGx research using a tube 
containing EDTA.  It is recommended that the blood sample be taken at the first 
opportunity after a subject has been randomised and provided informed consent for PGx 
research, but may be taken at any time while the subject is participating in the clinical 
study.

The PGx sample is labelled (or “coded”) with a study specific number that can be 
traced or linked back to the subject by the investigator or site staff.  Coded samples 
do not carry personal identifiers (such as name or social security number).  The 
blood sample is taken on a single occasion unless a duplicate sample is required due 
to inability to utilise the original sample.  
The DNA extracted from the blood sample may be subjected to sample quality control 
analysis.  This analysis will involve the genotyping of several genetic markers to confirm 
the integrity of individual samples.  If inconsistencies are noted in the analysis, then those 
samples may be destroyed.
The need to conduct PGx analysis may be identified after a study (or a set of studies) of 
albiglutide has been completed and the clinical study data reviewed.  In some cases, the 
samples may not be studied. e.g., no questions are raised about how people respond to 
albiglutide.
Samples will be stored securely and may be kept for up to 15 years after the last subject 
completes the study or GSK may destroy the samples sooner.  GSK or those working 
with GSK (for example, other researchers) will use samples collected from the study for 
the purpose stated in this protocol and in the informed consent form.  
Subjects can request their sample to be destroyed at any time.
Subject Withdrawal from Study
If a subject who has consented to participate in PGx research withdraws from the clinical 
study for any reason other than being lost to follow-up, the subject will be given a choice 
of one of the following options concerning the PGx sample, if already collected:

Continue to participate in the PGx research with the PGx sample retained for 
analysis 

Withdraw from the PGx research and destroy the PGx sample 
If a subject withdraws consent for PGx research or requests sample destruction for any 
reason, the investigator must complete the appropriate documentation to request sample
destruction within the timeframe specified by GSK and maintain the documentation in 

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the site study records. The investigator should forward the Pharmacogenetic Sample 
Destruction Request Form to GSK as directed on the form. This can be done at any time 
when a subject wishes to withdraw from the PGx research or have their sample destroyed 
whether during the study or during the retention period following close of the main study.
Screen and Baseline Failures
If a blood sample for PGx research has been collected and it is determined that the 
subject does not meet the entry criteria for participation in the clinical study, then the 
investigator should instruct the participant that their PGx sample will be destroyed. No 
forms are required to complete this process as it will be completed as part of the consent
and sample reconciliation process.  In this instance a sample destruction form will not be 
available to include in the site files.
Pharmacogenetics Analyses
1.
Specific genes may be studied that encode the drug targets, or drug mechanism of 
action pathways, drug metabolizing enzymes, drug transporters or which may
underpin adverse events, disease risk or drug response. These candidate genes may 
include a common set of ADME (Absorption, Distribution, Metabolism and 
Excretion) genes that are studied to determine the relationship between gene variants 
or treatment response and/or tolerance. 
In addition, continuing research may identify other enzymes, transporters, proteins or 
receptors that may be involved in response to albiglutide.  The genes that may code for 
these proteins may also be studied.
2.
Genome-wide scans involving a large number of polymorphic markers (e.g., single 
nucleotide polymorphisms) at defined locations in the genome, often correlated with 
a candidate gene, may be studied to determine the relationship between genetic 
variants and treatment response or tolerance. This approach is often employed when 
a definitive candidate gene(s) does not exist and/or the potential genetic effects are 
not well understood. 
If applicable and PGx research is conducted, appropriate statistical analysis methods will 
be used to evaluate pharmacogenetic data in the context of the other clinical data. Results 
of PGx investigations will be reported either as part of the main clinical study report or as 
a separate report. Endpoints of interest from all comparisons will be descriptively and/or 
graphically summarised as appropriate to the data.  A detailed description of the analysis 
to be performed will be documented in the study reporting and analysis plan (RAP) or in 
a separate pharmacogenetics RAP, as appropriate.  
Informed Consent
Subjects who do not wish to participate in the PGx research may still participate in the 
clinical study.  PGx informed consent must be obtained prior to any blood being taken for 
PGx research.

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Provision of Study Results and Confidentiality of Subject’s PGx Data
GSK may summarise the PGx research results in the clinical study report, or separately, 
or may publish the results in scientific journals. 
GSK does not inform the investigator, subject, or anyone else (e.g., family members, 
study investigators, primary care physicians, insurers, or employers) of individual 
genotyping results that are not known to be relevant to the subject’s medical care at the 
time of the study, unless required by law. This is due to the fact that the information 
generated from PGx studies is generally preliminary in nature, and therefore the 
significance and scientific validity of the results are undetermined.
References
Chung WH, Hung SL, Chen YT. Genetic predisposition of life-threatening antiepileptic-
induced skin reactions.  Expert Opin. Drug Saf. 2010; 9: 15-21.
Ferrell PB, McLeod HL.  Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson 
syndrome and toxic epidermal necrolysis: US FDA recommendations.  
Pharmacogenomics. 2008; 9: 1543-1546.
Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, 
Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses 
AD. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. 
Lancet. 2002; 359:1121-1122.
Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch 
L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ.  Genetic variants in the UDP-
glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J 
Clin Oncol 2004; 22: 1382-1388.
Liu CY, Chen PM, Chiou TJ, Liu JH, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, 
Wang WS.  UGT1A1*28 polymorphism predicts irinotecan-induced severe toxicities 
without affecting treatment outcome and survival in patients with metastatic colorectal 
carcinoma.  Cancer. 2008; 112: 1932-1940.
Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte 
C, Maxwell D, James I.  Association between presence of HLA-B*5701, HLA-DR7, and 
HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir.  
Lancet. 2002; 359:727-732.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jägel-Guedes E, 
Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, 
Thorborn D, Benbow A; PREDICT-1 Study Team.  HLA-B*5701 screening for 
hypersensitivity to abacavir. N Engl J Med. 2008; 358; 568-579
Schulz C, Heinemann V, Schalhorn A, Moosmann N, Zwingers T, Boeck S, Giessen C, 
Stemmler HJ. UGT1A1 gene polymorphism: Impact on toxicity and efficacy of 
irinotecan-based regimens in metastatic colorectal cancer.  World J. Gastroenterol. 2009; 
15: 5058-5066.

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11.2.
Appendix 2: Liver Chemistry Stopping and Follow-up 
Criteria
Phase III-IV Liver Safety Algorithms
ALT>3xULN
plus 
bilirubin >2x 
ULN (>35%
direct) (or plus
INR >1.5, if   
measured)*
No
Yes
Yes
•Instruct subject to stop investigational product (IP)
•Notify GSK within 24h and arrange clinical followup 
within 24-72h
•Perform liver chemistries and liver event follow up 
assessments (serology, PK sample etc as in protocol) 
•Complete liver event CRF, SAE data collection tool if 
appropriate, and liver imaging and/or biopsy CRFs if  
tests performed.
•Obtain weekly liver chemistries [**as far as possible in 
these subjects] until resolved, stabilised or returned to 
baseline 
•Withdraw subject from study after monitoring 
complete unless protocol has option to restart drug
•Instruct subject to stop investigational product (IP)
•Notify GSK and arrange clinical followup within 24h
•Perform liver chemistries and liver event follow up 
assessments (serology, PK sample etc as in protocol) 
•Report as SAE (excl. hepatic impairment or cirrhosis 
studies) and complete liver event CRF, SAE data 
collection tool, and liver imaging and/or biopsy CRFs if 
tests performed.
•Obtain twice weekly liver chemistries until resolved, 
stabilised or returned to baseline values
•Consultation with hepatologist/specialist recommended
•Withdraw subject from study after monitoring 
complete unless protocol has option to restart drug
Hepatitis 
symptoms
or rash?
No
Able to 
monitor 
weekly for 
4 weeks?
Yes
No**
Yes
Continue IP
Obtain twice 
monthly liver 
chemistries until 
normalised or 
back to baseline 
values
Yes
Yes
ALT<3xULN 
+ bilirubin 
<2xULN 
after ≤ 4 
wks?
Yes
ALT 
>5xULN 
but 
<8xULN
No
ALT  
>8xULN
Yes
ALT >5 
and 
<8xULN 
for > 2 
wks
Yes
No
ALT>3xULN 
but <5xULN + 
bilirubin 
<2xULN+no 
symptoms
No
Able to 
monitor 
weekly for 
> 2 wks?
No
No
Notify GSK within 24h 
to discuss subject 
safety; continue IP;
check liver chemistry 
weekly for 4 weeks
Yes
No
*INR value not applicable to subjects on anticoagulants

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11.3.
Appendix 3: Immunogenicity Testing
The immunogenicity of albiglutide will be evaluated by the following testing schemes 
and assays. Samples will be obtained from all subjects.
Sample Testing Schemes
Samples for immunogenicity testing will be obtained from all subjects before 
administration of the investigational product at Baseline and in accordance with the 
schedule in the Time and Events table. 
The presence of anti-albiglutide antibodies will be assessed using a qualified screening 
enzyme-linked immunosorbent assay (ELISA). If serum samples contain anti-albiglutide 
antibodies, they will be further analysed for the specificity of antibodies by a 
confirmation assay. Confirmed positive samples will be titrated to obtain the titre of 
antibodies. To test whether the anti-albiglutide antibodies cross-react with endogenous 
glucagon-like peptide (GLP-1) and albumin, positive samples will be tested in 
anti-GLP-1 and anti-HA screening ELISAs. In addition, anti-albiglutide-positive samples 
will be tested in neutralisation antibody assays for neutralising activity against drug 
(albiglutide).
Antibody Detection Assays
The detection assays are ELISA based, which include screening, confirmation and 
titration assays (anti-HA is screening only). The procedures for the albiglutide 
immunoglobulin (Ig) (GAM) ELISA are described below:
1. 96-well ELISA plates are coated with albiglutide overnight.
2. Samples are diluted 1:50 and incubated on the blocked plates for 3 hours.
3. A horseradish peroxidase-labeled antihuman Ig (GAM) antibody is used as a 
detection antibody.
4. A tetramethylbenzidine substrate is used to produce the enzymatic reaction which 
is followed by an acid stop procedure.
5. The plates are read at 450 nm.
6. A positive control (positive control, normal serum pool spiked with anti-GLP-1 
antibody) and negative control (negative control, pool normal human sera) are 
included on each assay plate.
7. Relative optical density values are calculated by dividing the mean optical density 
of sample or positive control by the mean optical density of the negative control.
Screening
Screening comprises determination of a cutoff value for drug-naïve type 1 diabetes 
mellitus subjects and identification of serum samples potentially positive for anti 
albiglutide antibody.

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Confirmation
Specificity of serum antibodies is confirmed by competing their binding to albiglutide 
immobilised on plates with excess albiglutide in solution. If the sample is still positive 
after the confirmation assay, the sample will be reported as positive and further analysis 
will be done by the titration and neutralising antibody assays.
Titration
Confirmed positive samples (in confirmation) will be titrated to obtain a titre of 
anti-albiglutide antibody.
Neutralising Antibody Assays
The neutralising antibody assays are cell-based assays, which include screening, 
confirmation, and titration assays. Albiglutide-neutralising activity is measured by adding 
serum samples pre-incubated with a fixed concentration of albiglutide to GLP-1 
receptor/CRE (cyclic adenosine monophosphate response element)-luciferase transfected 
cells and measuring luminescence intensity after 3 hours of incubation. Samples 
possessing neutralising activity will generate a reduced signal and will be further tested in 
the confirmation (specificity) assay if the generated signal is positive (i.e., below the 
assay’s screening cutoff).
Immunogenicity Testing Report
The immunogenicity testing report will include the incidence of immunogenicity, 
incidence of neutralising antibodies, and the antibody titres (anti-drug antibody 
binding and neutralisation).

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11.4.
Appendix 4: Audit of Diabetes Dependent Quality of Life 
(AddQoL)
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, 
which are protected by third party copyright laws and therefore have been excluded.

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11.5.
Appendix 5: Country Specific Requirements
Country-Specific Requirements 
No country-specific requirements exist.

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11.6.
Appendix 6: Protocol Amendment Changes
11.6.1.
Changes Resulting from Protocol Amendment 01
This amendment is applicable to all participating countries.
Summary of Changes
1. Update to SAE Contact information.
2. Correction of typographical error in Exclusion criterion 11.
3. Clarification wording added to the treatment compliance section to highlight that 
unused investigational product does not need to be returned at Week 2.  There is 
no dispensing visit at Week 2 (as per Time and Events Table) so subjects may 
have been left without study medication until the next dispensing visit (Week 4).
4. Correction of footnotes 1 and 2 to Table 4 which had erroneously been 
transposed.
5. Clarification that insulin usage needs to be captured in the diary for at least 3 days 
prior to Baseline. 
List of Specific Changes
Sponsor Information Page
Original text:
Sponsor Serious Adverse Events (SAE)* Contact Information:
GCSP Case Management Group
Telephone: 
e-mail address: 
*SAEs to be submitted via the eCRF.  Please see Study Procedures Manual for details. 
Amended Text:
Sponsor Serious Adverse Events (SAE)* Contact Information:
GCSP Case Management Group
Telephone: 
e-mail address: 
*SAEs to be submitted via the eCRF.  
PPD
PPD
PPD
PPD

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Please see Study Procedures Manual for details regarding submission of back-up paper 
SAE CRF pages. 
Section 4.3, Criterion 11
Original text:
Any clinically significant co-morbidity or abnormality (including psychiatric disorder, 
any other autoimmune endocrinopathy e.g., primary autoimmune hypothyroidism, 
hyperadrenalism, coeliac disease etc) that in the opinion of the Investigator, may pose 
additional risk in administering study medication or trial participation
Amended text:
Any clinically significant co-morbidity or abnormality (including psychiatric disorder, 
any other autoimmune endocrinopathy e.g., primary autoimmune hypothyroidism, 
hypoadrenalism, coeliac disease etc) that in the opinion of the Investigator, may pose 
additional risk in administering study medication or trial participation
Section 5.5 Treatment Compliance, paragraph 1
Original text:
Investigational product accountability will be done for albiglutide/matching placebo at 
each study visit after the baseline visit through the end-of-treatment visit (at Week 52) 
inclusive. Subjects will be instructed to return all unused investigational product and used 
injector pens at each visit in order to perform drug accountability and determine 
compliance.
Amended Text:
Investigational product accountability will be done for albiglutide/matching placebo at 
each study visit after the baseline visit through the end-of-treatment visit (at Week 52) 
inclusive. Subjects will be instructed to return all unused investigational product and used 
injector pens at each visit (with the exception of Week 2 where only used injector pens 
need to be returned) in order to perform drug accountability and determine compliance.
Time and Events Table  - Telephone calls, footnotes 1 and 2

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Original Text:
Table 7
Time and Events Table –  Telephone Calls
Study 
Procedure
Treatment
(telephone calls to be performed as a minimum at the time points specified (3 days) and as required for 
appropriate management of the subject
Week
12
3
5
7
9
10
11
12
13
14
151
221
341
461
1.
Every 3-5 days during the first 2 weeks and for 2 weeks following study drug increase at Week 6
2.
Telephone calls  as necessary from Week 16 through to the end of the study to advise subjects on insulin dose adjustments, adverse event (AE) monitoring, hypoglycaemia and 
diabetic ketoacidosis monitoring
Amended text:
Table 8
Time and Events Table –  Telephone Calls
Study 
Procedure
Treatment
(telephone calls to be performed as a minimum at the time points specified (3 days) and as required for 
appropriate management of the subject
Week
11
3
5
7
9
10
11
12
13
14
152
222
342
462
1.
Every 3-5 days during the first 2 weeks and for 2 weeks following study drug increase at Week 6
2.
Telephone calls  as necessary from Week 16 through to the end of the study to advise subjects on insulin dose adjustments, adverse event (AE) monitoring, hypoglycaemia and 
diabetic ketoacidosis monitoring

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Section 6.3.2.5, 2nd sentence
Original Text:
Subjects will record their daily insulin use in a diary. This information will be collected at 
Baseline, daily for the first 2 weeks and for at least 3 days preceding the telephone 
calls/visits at Week 3 through to Week 16, Week 22, Week 28, Week 34, Week 40, Week 
46, Week 52 and Week 64.
Amended text:
Subjects will record their daily insulin use in a diary. This information will be collected 
for at least 3 days before at Baseline, daily for the first 2 weeks and for at least 3 days 
preceding the telephone calls/visits at Week 3 through to Week 16, Week 22, Week 28, 
Week 34, Week 40, Week 46, Week 52 and Week 64.

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11.6.2.
Changes Resulting from Protocol Amendment 02
This amendment is applicable to UK sites only.
SUMMARY OF CHANGES
Change to one of the acceptable methods of contraception at the request of the MHRA.
List of Specific Changes
Section 4.2. Inclusion criterion 6
Original text:
Male condom combined with a female diaphragm, either with or without a vaginal 
spermicide.
Amended Text:
Male condom combined with a female diaphragm, either with or without a vaginal 
spermicide. [UK only: this method of contraception is acceptable only if used with a 
vaginal spermicide].