A Study to Determine the Long Term Safety and Efficacy of Albiglutide in Combination With Oral Monotherapy Antihyperglycemic Medications in Japanese Patients With Type 2 Diabetes Mellitus

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01777282
• Collaborator: (none)
• Enrollment: 374
• Locations: 49
• Arms: 5
• Actual Duration (Months): 23.1
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This study is designed to examine the long term safety and efficacy of weekly subcutaneously injected albiglutide in combination with a single oral antidiabetic drug for 52 weeks in Japanese subjects with type 2 diabetes mellitus.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus	Drug: Albiglutide; Drug: Sulfonylurea; Drug: Biguanide; Drug: Glinide; Drug: Thiazolidinedione; Drug: Alpha-glucosidase inhibitor	Phase 3

Detailed Description

This study is designed to examine the long term safety and efficacy of weekly subcutaneously injected albiglutide in combination with a single oral antidiabetic drug for 52 weeks in Japanese subjects with type 2 diabetes mellitus. Subjects with a historical diagnosis of type 2 diabetes mellitus who are inadequately controlled on a single oral antidiabetic agent will be recruited into the study. Subjects will continue on their single antidiabetic agent and once weekly albiglutide will be added.

Study Design

• Study Type: Interventional
• Actual Enrollment: 374 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52-Week, Open-Label, Multicenter Study to Determine the Long Term Safety and Efficacy of Albiglutide in Combination With Monotherapy of Oral Antihyperglycemic Medications in Japanese Patients With Type 2 Diabetes Mellitus
• Actual Study Start Date: Feb 23, 2013
• Actual Primary Completion Date: Jan 27, 2015
• Actual Study Completion Date: Jan 27, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Albiglutide + Sulfonylurea Albiglutide in combination with background sulfonylurea	Drug: Albiglutide; Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It 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. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.; Drug: Sulfonylurea; Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.
Active Comparator: Albiglutide + Biguanide Albiglutide in combination with background biguanide	Drug: Albiglutide; Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It 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. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.; Drug: Biguanide; Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.
Active Comparator: Albiglutide + Glinide Albiglutide in combination with background glinide	Drug: Albiglutide; Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It 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. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.; Drug: Glinide; Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.
Active Comparator: Albiglutide + Thiazolidinedione Albiglutide in combination with background thiazolidinedione	Drug: Albiglutide; Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It 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. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.; Drug: Thiazolidinedione; Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.
Active Comparator: Albiglutide + Alpha-glucosidase inhibitor Albiglutide in combination with background alpha-glucosidase inhibitor	Drug: Albiglutide; Albiglutide is a fixed-dose, fully disposable pen injector system for delivery of albiglutide from a prefilled dual chamber glass cartridge that is an integral part of the pen. It 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. The subject will inject albiglutide 30 mg weekly for 52 weeks (with optional uptitration to 50 mg weekly) subcutaneously into the abdomen, alternating between left and right sides. The pen is designed to work with standard pen needles.; Drug: Alpha-glucosidase inhibitor; Single oral antidiabetic drug as a background therapy, to be continued as previously prescribed.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) [From Baseline through Week 52]

   An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs. Non-serious hypoglycemia events are not included.

2. Number of Participants With Any Hypoglycemic Event [From Baseline through Week 52]

   Hypoglycemia events are defined with respect to low plasma glucose level, mostly accompanied by typical symptoms and/or assistance needed from third party with glucose administration. These events were reported by the investigators upon verification of the plasma glucose levels, symptoms and assistance recorded by the participants, and/or plasma glucose values obtained from laboratory evaluations.

Secondary Outcome Measures

1. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52 [Baseline and Week 52]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis.

2. Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0% at Week 52) [Week 52]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis. Clinically meaningful levels of response in HbA1c are defined as <6.5% and <7.0%.

3. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 [Baseline and Week 52]

   FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the FPG value at Week 52 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline FPG observation carried forward for the analysis.

4. Change From Baseline in Body Weight at Week 52 [Baseline and Week 52]

   The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 52 minus the value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline weight observation carried forward for the analysis.

5. Time to Study Withdrawal Due to Hyperglycemia [Week 52]

   Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose >=280 mg/dL (>=15.5 mmol/L) from >=Week 2 to <Week 12 or >=230 mg/dL (>=12.8 mmol/L) from >=Week 12 to <Week 52.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with diagnosis of Type 2 Diabetes Mellitus, who are experiencing inadequate glycemic control and receiving treatment with a stable dose of a single oral antidiabetic medication

• Body mass index (BMI) 17 to 40 kg/ m2 inclusive

• Subjects with an HbA1c between 7.0% and 10.0% at Screening

• Creatinine clearance >30 mL/min (calculated using the Cockcroft-Gault formula)

Exclusion Criteria:

• History of type 1 diabetes mellitus

• Female subject is pregnant, lactating, or <6 weeks postpartum

• Clinically significant cardiovascular and/or cerebrovascular disease

• Current ongoing symptomatic biliary disease, clinical signs or symptoms of pancreatitis, or a history of chronic or acute pancreatitis, as determined by the investigator

• Serum amylase >=3 ×ULN and/or serum lipase >=2 × ULN and/or subject is experiencing any symptoms possibly related to pancreatitis

• Prior use of a GLP-1R agonist or DPP-IV inhibitor within 6 months before Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Aichi		Japan	456-0058
2	GSK Investigational Site	Chiba		Japan	263-0043
3	GSK Investigational Site	Ehime		Japan	792-8586
4	GSK Investigational Site	Fukuoka		Japan	810-0014
5	GSK Investigational Site	Fukuoka		Japan	815-8588
6	GSK Investigational Site	Fukuoka		Japan	819-0168
7	GSK Investigational Site	Fukushima		Japan	960-0418
8	GSK Investigational Site	Fukushima		Japan	963-8851
9	GSK Investigational Site	Gunma		Japan	370-3573
10	GSK Investigational Site	Gunma		Japan	379-0116
11	GSK Investigational Site	Hokkaido		Japan	040-8585
12	GSK Investigational Site	Hokkaido		Japan	070-0002
13	GSK Investigational Site	Ibaraki		Japan	300-0835
14	GSK Investigational Site	Ibaraki		Japan	311-0113
15	GSK Investigational Site	Kagawa		Japan	760-0076
16	GSK Investigational Site	Kagoshima		Japan	890-0061
17	GSK Investigational Site	Kanagawa		Japan	232-0064
18	GSK Investigational Site	Kanagawa		Japan	235-0045
19	GSK Investigational Site	Kanagawa		Japan	252-0302
20	GSK Investigational Site	Kanagawa		Japan	253-0044
21	GSK Investigational Site	Kochi		Japan	780-0088
22	GSK Investigational Site	Kumamoto		Japan	862-0960
23	GSK Investigational Site	Kumamoto		Japan	867-0041
24	GSK Investigational Site	Kyoto		Japan	600-8558
25	GSK Investigational Site	Kyoto		Japan	601-1495
26	GSK Investigational Site	Kyoto		Japan	601-8325
27	GSK Investigational Site	Miyagi		Japan	980-0021
28	GSK Investigational Site	Miyagi		Japan	985-0852
29	GSK Investigational Site	Nagano		Japan	399-0006
30	GSK Investigational Site	Nagano		Japan	399-0036
31	GSK Investigational Site	Oita		Japan	870-0039
32	GSK Investigational Site	Okinawa		Japan	900-0029
33	GSK Investigational Site	Osaka		Japan	530-0012
34	GSK Investigational Site	Osaka		Japan	536-0023
35	GSK Investigational Site	Osaka		Japan	538-0044
36	GSK Investigational Site	Osaka		Japan	577-0803
37	GSK Investigational Site	Osaka		Japan	582-0019
38	GSK Investigational Site	Saitama		Japan	332-0012
39	GSK Investigational Site	Saitama		Japan	350-0035
40	GSK Investigational Site	Saitama		Japan	350-0851
41	GSK Investigational Site	Saitama		Japan	354-0031
42	GSK Investigational Site	Saitama		Japan	355-0321
43	GSK Investigational Site	Saitama		Japan	358-0011
44	GSK Investigational Site	Shizuoka		Japan	424-0855
45	GSK Investigational Site	Tochigi		Japan	329-0433
46	GSK Investigational Site	Tokyo		Japan	103-0002
47	GSK Investigational Site	Tokyo		Japan	103-0027
48	GSK Investigational Site	Tokyo		Japan	125-0054
49	GSK Investigational Site	Tokyo		Japan	143-0015

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01777282
• Other Study ID Numbers: 116170
• First Posted: Jan 28, 2013
• Last Update Posted: May 3, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: albiglutide; Japanese; glucagon-like peptide-1; GSK716155
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Biguanides; 2,4-thiazolidinedione; Glycoside Hydrolase Inhibitors; rGLP-1 protein

Study Results

Participant Flow

Recruitment Details	A total of 360 participants with type 2 diabetes mellitus (T2DM) were planned and 374 participants were enrolled and analyzed in the Safety Population; the Safety Population and Intent-to-Treat Population were identical in this study.
Pre-assignment Detail	Eligible participants entered a 2-week Screening Period; a 52-week Treatment Period and an 8-week Follow-up (FU) Period.

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Period Title: Overall Study
STARTED	120	67	65	61	61
Completing Treatment Period	109	63	59	59	54
Completing Follow-up Period	109	63	59	59	54
COMPLETED	109	63	59	59	54
NOT COMPLETED	11	4	6	2	7

Baseline Characteristics

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)	Total
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Total of all reporting groups
Overall Participants	120	67	65	61	61	374
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.5 (9.19)	57.0 (8.55)	55.7 (11.07)	59.0 (10.54)	57.4 (10.47)	57.7 (9.89)
Sex: Female, Male (Count of Participants)
Female	33 27.5%	22 32.8%	22 33.8%	11 18%	20 32.8%	108 28.9%
Male	87 72.5%	45 67.2%	43 66.2%	50 82%	41 67.2%	266 71.1%
Race/Ethnicity, Customized (Number) [Number]
Asian - Japanese Heritage	120 100%	67 100%	65 100%	61 100%	61 100%	374 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)
Description	An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of non-serious AEs and SAEs. Non-serious hypoglycemia events are not included.
Time Frame	From Baseline through Week 52

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study treatment.

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Measure Participants	120	67	65	61	61
Any AE	97 80.8%	47 70.1%	58 89.2%	49 80.3%	43 70.5%
Any SAE	2 1.7%	0 0%	1 1.5%	2 3.3%	3 4.9%

2. Primary Outcome

Title	Number of Participants With Any Hypoglycemic Event
Description	Hypoglycemia events are defined with respect to low plasma glucose level, mostly accompanied by typical symptoms and/or assistance needed from third party with glucose administration. These events were reported by the investigators upon verification of the plasma glucose levels, symptoms and assistance recorded by the participants, and/or plasma glucose values obtained from laboratory evaluations.
Time Frame	From Baseline through Week 52

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study treatment.

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Measure Participants	120	67	65	61	61
Number [Participants]	17 14.2%	1 1.5%	4 6.2%	2 3.3%	0 0%

3. Secondary Outcome

Title	Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 52
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the value at Week 52 minus the value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (Last Observation Carried Forward) Population: all enrolled participants who received at least 1 dose of study medication and who had at least one HbA1c post-Baseline assessment.

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Measure Participants	120	67	65	61	60
Mean (Standard Deviation) [Percentage of HbA1c in the blood]	-1.04 (0.657)	-0.94 (0.623)	-0.95 (0.836)	-1.42 (0.771)	-1.39 (0.770)

4. Secondary Outcome

Title	Percentage of Participants Achieving Clinically Meaningful Levels of HbA1c (i.e., the Percentage of Participants Achieving Treatment Goal of <6.5% and <7.0% at Week 52)
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3 month period. The Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline HbA1c observation carried forward for the analysis. Clinically meaningful levels of response in HbA1c are defined as <6.5% and <7.0%.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (Last Observation Carried Forward) Population

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Measure Participants	120	67	65	61	60
HbA1c <6.5%	20.0 16.7%	26.9 40.1%	24.6 37.8%	45.9 75.2%	26.2 43%
HbA1c <7.0%	54.2 45.2%	59.7 89.1%	52.3 80.5%	80.3 131.6%	67.2 110.2%

5. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52
Description	FPG is an indicator of efficacy. The Baseline FPG value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the FPG value at Week 52 minus the FPG value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline FPG observation carried forward for the analysis.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (Last Observation Carried Forward) Population. Only those participants with valid post-Baseline results (within 14 days of last exposure to treatment) were analyzed.

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Measure Participants	120	67	65	61	59
Mean (Standard Deviation) [Milligrams per deciliter (mg/dL)]	-16.4 (28.52)	-24.3 (19.98)	-16.4 (30.37)	-32.1 (27.21)	-33.2 (28.38)

6. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 52
Description	The Baseline body weight value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the body weight value at Week 52 minus the value at Baseline. Participants who discontinued from study treatment before Week 52 had their last on-treatment, post-Baseline weight observation carried forward for the analysis.
Time Frame	Baseline and Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (Last Observation Carried Forward) Population

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Measure Participants	120	67	65	61	60
Mean (Standard Deviation) [Kilograms (kg)]	0.25 (2.167)	-0.33 (2.082)	-0.04 (2.405)	0.52 (2.823)	-0.13 (2.620)

7. Secondary Outcome

Title	Time to Study Withdrawal Due to Hyperglycemia
Description	Participants who experienced persistent hyperglycemia after uptitration were to be withdrawn from the study. Hyperglycemia is defined as a fasting plasma glucose >=280 mg/dL (>=15.5 mmol/L) from >=Week 2 to <Week 12 or >=230 mg/dL (>=12.8 mmol/L) from >=Week 12 to <Week 52.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (Last Observation Carried Forward) Population. Only participants who were withdrawn due to hyperglycemia were analyzed.

Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)	Albiglutide Plus (+) Background OAD (Biguanide)	Albiglutide Plus (+) Background OAD (Glinide)	Albiglutide Plus (+) Background OAD (Thiazolidinedione)	Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.	Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
Measure Participants	1	0	2	0	0
Mean (Standard Deviation) [Weeks]	13.0 (NA)	16.5 (3.54)

Adverse Events

Time Frame	On-therapy non-serious adverse events (AEs) and serious adverse events (SAEs) with an onset date on or after the start date of study treatment and within 56 days after the date of the last dose of study treatment, are summarized through Week 52.
Adverse Event Reporting Description	The non-serious AEs and SAEs are reported for the Safety Population, which comprised of all participants who received at least 1 dose of study treatment; par. underwent uptitration of albiglutide from 30 mg to 50 mg weekly based on glycemic parameters.
Arm/Group Title	Albiglutide Plus (+) Background OAD (Sulfonylurea)		Albiglutide Plus (+) Background OAD (Biguanide)		Albiglutide Plus (+) Background OAD (Glinide)		Albiglutide Plus (+) Background OAD (Thiazolidinedione)		Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
Arm/Group Description	Participants received current regimen of 30 milligrams (mg) albiglutide + sulfonylurea (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.		Participants received current regimen of 30 mg albiglutide + biguanide (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.		Participants received current regimen of 30 mg albiglutide + glinide as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.		Participants received current regimen of 30 mg albiglutide + thiazolidinedione as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.		Participants received current regimen of 30 mg albiglutide + α-glucosidase inhibitor as a subcutaneous injection weekly (with titration to 50 mg at Week 4 or later based on specific guidelines on glycemic control) through Week 52.
All Cause Mortality
	Albiglutide Plus (+) Background OAD (Sulfonylurea)		Albiglutide Plus (+) Background OAD (Biguanide)		Albiglutide Plus (+) Background OAD (Glinide)		Albiglutide Plus (+) Background OAD (Thiazolidinedione)		Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Albiglutide Plus (+) Background OAD (Sulfonylurea)		Albiglutide Plus (+) Background OAD (Biguanide)		Albiglutide Plus (+) Background OAD (Glinide)		Albiglutide Plus (+) Background OAD (Thiazolidinedione)		Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/120 (1.7%)		0/67 (0%)		1/65 (1.5%)		2/61 (3.3%)		3/61 (4.9%)
General disorders
Chest discomfort	0/120 (0%)		0/67 (0%)		0/65 (0%)		0/61 (0%)		1/61 (1.6%)
Hepatobiliary disorders
Cholelithiasis	0/120 (0%)		0/67 (0%)		0/65 (0%)		0/61 (0%)		1/61 (1.6%)
Infections and infestations
Anal abscess	1/120 (0.8%)		0/67 (0%)		0/65 (0%)		0/61 (0%)		0/61 (0%)
Urinary tract infection	1/120 (0.8%)		0/67 (0%)		0/65 (0%)		0/61 (0%)		0/61 (0%)
Injury, poisoning and procedural complications
Femur fracture	0/120 (0%)		0/67 (0%)		0/65 (0%)		0/61 (0%)		1/61 (1.6%)
Foot fracture	0/120 (0%)		0/67 (0%)		0/65 (0%)		1/61 (1.6%)		0/61 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon Adenoma	0/120 (0%)		0/67 (0%)		1/65 (1.5%)		0/61 (0%)		0/61 (0%)
Papillary thyroid cancer	0/120 (0%)		0/67 (0%)		0/65 (0%)		1/61 (1.6%)		0/61 (0%)
Other (Not Including Serious) Adverse Events
	Albiglutide Plus (+) Background OAD (Sulfonylurea)		Albiglutide Plus (+) Background OAD (Biguanide)		Albiglutide Plus (+) Background OAD (Glinide)		Albiglutide Plus (+) Background OAD (Thiazolidinedione)		Albiglutide Plus (+) Background OAD (α-Glucosidase Inhibitor)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/120 (56.7%)		31/67 (46.3%)		38/65 (58.5%)		35/61 (57.4%)		24/61 (39.3%)
Eye disorders
Diabetic retinopathy	8/120 (6.7%)		3/67 (4.5%)		0/65 (0%)		5/61 (8.2%)		4/61 (6.6%)
Gastrointestinal disorders
Constipation	15/120 (12.5%)		1/67 (1.5%)		4/65 (6.2%)		5/61 (8.2%)		2/61 (3.3%)
Diarrhoea	3/120 (2.5%)		6/67 (9%)		1/65 (1.5%)		0/61 (0%)		2/61 (3.3%)
Infections and infestations
Nasopharyngitis	37/120 (30.8%)		19/67 (28.4%)		30/65 (46.2%)		19/61 (31.1%)		17/61 (27.9%)
Bronchitis	4/120 (3.3%)		4/67 (6%)		1/65 (1.5%)		2/61 (3.3%)		3/61 (4.9%)
Pharyngitis	4/120 (3.3%)		2/67 (3%)		2/65 (3.1%)		4/61 (6.6%)		2/61 (3.3%)
Gastroenteritis	6/120 (5%)		1/67 (1.5%)		2/65 (3.1%)		2/61 (3.3%)		0/61 (0%)
Injury, poisoning and procedural complications
Contusion	8/120 (6.7%)		0/67 (0%)		1/65 (1.5%)		0/61 (0%)		0/61 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	17/120 (14.2%)		1/67 (1.5%)		4/65 (6.2%)		2/61 (3.3%)		0/61 (0%)
Musculoskeletal and connective tissue disorders
Back pain	4/120 (3.3%)		2/67 (3%)		1/65 (1.5%)		5/61 (8.2%)		0/61 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.