Dose Ranging Study of Albiglutide in Japanese Subjects

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ClinicalTrials.gov Identifier: NCT01098461

Recruitment Status : Completed

First Posted : April 2, 2010

Results First Posted : July 1, 2014

Last Update Posted : January 13, 2017

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

Study Description

Brief Summary:

This is a randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging study evaluating the dose response, efficacy and safety of subcutaneously injected GSK716155 (albiglutide) in Japanese subjects with type 2 diabetes mellitus.

Condition or disease	Intervention/treatment	Phase
Diabetes Mellitus, Type 2	Biological: albiglutide Biological: placebo	Phase 2

Detailed Description:

This is a Phase IIb, randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging, superiority study evaluating the dose response, efficacy and safety of weekly and every other week subcutaneously injected GSK716155 (albiglutide) in subjects with type 2 diabetes mellitus.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	215 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Dose Finding Study of GSK716155 Versus Placebo in the Treatment of Type 2 Diabetes Mellitus
Study Start Date :	April 2010
Actual Primary Completion Date :	May 2011
Actual Study Completion Date :	May 2011

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Type 2 diabetes

Drug Information available for: Albiglutide

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: albiglutide 15mg weekly once weekly subcutaneous injection of albiglutide 15mg	Biological: albiglutide subcutaneous injection of albiglutide Other Names: placebo albiglutide 30mg weekly albiglutide 15mg weekly albiglutide 30mg every other week
Active Comparator: albiglutide 30mg weekly once weekly subcutaneous injection of albiglutide 30mg	Biological: albiglutide subcutaneous injection of albiglutide Other Names: placebo albiglutide 30mg weekly albiglutide 15mg weekly albiglutide 30mg every other week
Active Comparator: albiglutide 30mg every other week subcutaneous injection of 30mg albiglutide every other week	Biological: albiglutide subcutaneous injection of albiglutide Other Names: placebo albiglutide 30mg weekly albiglutide 15mg weekly albiglutide 30mg every other week
Placebo Comparator: placebo once weekly subcutaneous injection of placebo to match albiglutide	Biological: placebo subcutaneous injection of placebo to match albiglutide

Outcome Measures

Primary Outcome Measures :

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16 [ Time Frame: Baseline and Week 16 ]
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 16 minus the value at Baseline. Based on Analysis of Covariance (ANCOVA): Change = treatment + Baseline HbA1c + prior therapy. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.

Secondary Outcome Measures :

Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline; Week 4, Week 8, Week 12, and Week 16 ]
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 16 minus the value at Baseline. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement was used to impute the missing measurement. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline; Week 4, Week 8, Week 12, and Week 16 ]
The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Change From Baseline in Body Weight at Week 4, 8, 12, and 16 [ Time Frame: Baseline; Week 4, Week 8, Week 12, and Week 16 ]
The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values.
Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16 [ Time Frame: Week 4, Week 8, Week 12, and Week 16 ]
The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5% and <7%) were assessed.
Mean Clearance of Albiglutide [ Time Frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 ]
Clearance is defined as the volume of plasma cleared of albiglutide per unit time. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, pharmacokinetic (PK) samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.
Mean Volume of Distribution of Albiglutide [ Time Frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 ]
Volume of distribution is defined as the apparent volume in which albiglutide is distributed. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.
Mean Absorption Rate of Albiglutide [ Time Frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 ]
Absorption rate is defined as the rate at which albiglutide enters the blood circulation. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. Modeled population PK data are presented; data were analyzed using a non-linear mixed effect modeling approach. A one-compartment PK model with first-order absorption and elimination processes was selected to describe GSK716155 PK.
Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG [ Time Frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24 ]
EC50 is defined as the concentration of albiglutide that give a half-maximal HbA1c and FPG response. Samples were collected prior to the administration of study medication on dosing days (Weeks 0, 1, 4, 5, 8, 12, and 13) and on the day of the clinic visit at Weeks 16, 20, and 24. At Weeks 0, 1, 4, 8, and 12, PK samples were collected immediately prior to dosing if a dose was scheduled for that week. At Weeks 16, 20, and 24, PK samples were collected at any time during the visit. The Week 5 post-dose PK sampling was performed any time between Weeks 4 and 6, within 2 to 5 days after administration of a dose; Week 13 post-dose PK sampling was performed any time between Weeks 12 and 14, within 2 to 5 days after administration of a dose of study medication. EC50 estimates used PK data as well as HbA1c and FPG efficacy data. EC50 was estimated from an inhibitory Emax (maximal possible effect of albiglutide) model.

Eligibility Criteria

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Ages Eligible for Study:	20 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject with a historical diagnosis of type 2 diabetes mellitus who is currently treated with diet and exercise only or one OAD
BMI ≥18 kg/m2 and <35 kg/m2 at Screening
HbA1c between 7.0% and 10.0%, inclusive
Fasting C-peptide ≥0.8 ng/mL (≥0.26 nmol/L)
Female subjects of childbearing potential must be practicing adequate contraception .
Able and willing to monitor his/her own blood glucose concentrations with a home glucose monitor.
Able and willing to provide written informed consent

Exclusion Criteria:

Diagnosis of type 1 diabetes mellitus
Uncorrected thyroid dysfunction
Previous use of insulin within one month prior to screening, or more than seven total days of insulin treatment within three months prior to screening
Clinically significantly cardiovascular and/or cerebrovascular disease including, but not limited to the following:
- Previous history of stroke or transient ischemic attack
- Active, unstable coronary heart disease within the past six months before Screening
- Documented myocardial infarction within one year before Screening
- Any cardiac surgery including percutaneous transluminal coronary angioplasty, coronary stent placement, or coronary artery bypass graft surgery within one year before Screening
- Unstable angina
- Clinically significant arrhythmia or valvular heart disease
- Current heart failure NYHA class II to IV
- Resting systolic pressure >160 mm Hg or diastolic pressure >95 mm Hg at Screening
- ECG criteria at Screening
Heart rate: <40 and >110 bpm
PR interval: <120 and > 210 msec
QRS interval: <70 and >120 msec
QTc interval (Bazett): >450 msec or >480 msec with bundle branch block
Fasting triglyceride level >400 mg/dL at Screening
AST or ALT >2xULN, ALP and bilirubin >1.5xULN (except known Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin)
If female, is currently lactating, within 6 weeks post-partum, pregnant, or actively trying to become pregnant
Has significant renal disease as manifested by one or more of the following:
- Creatinine clearance at screening <60 mL/min (calculated by Cockcroft-Gault formula) at Screening
- Known loss of a kidney either by surgical ablation, injury or disease level
A hemoglobinopathy that may affect determination of HbA1c level
History of treated diabetic gastroparesis
History of significant gastrointestinal surgery, including gastric bypass and banding, or surgeries thought to significantly affect upper gastrointestinal function
Current ongoing symptomatic biliary disease or history of acute/chronic pancreatitis.
Lipase and amylase at Screening > ULN
Severe diabetic neuropathy, preproliferative retinopathy or proliferative retinopathy, history of ketoacidosis or hyperosmolar coma
History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 3 years before Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)
Acute or chronic history of liver disease, positive hepatitis B surface antigen (HBsAg) or positive hepatitis C testing at Screening
Current and history of alcohol or substance abuse
Clinically significant anaemia or any other abnormal haematological profile that is considered by the investigator to be clinically significant
Prior use of a GLP-1 analog
Known allergy to any formulation excipients, or Baker's yeast, or history of drug, or other allergy which, in the opinion of the responsible study physician, contradicts participation
History of or family history of medullary carcinoma of the thyroid.
History of or family history of multiple endocrine neoplasia type 2
Receipt of any investigational drug within the 12 weeks before Screening

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01098461

Locations

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Japan
GSK Investigational Site
Aichi, Japan, 466-0815
GSK Investigational Site
Ehime, Japan, 790-0067
GSK Investigational Site
Fukuoka, Japan, 810-0001
GSK Investigational Site
Fukuoka, Japan, 811-1346
GSK Investigational Site
Fukuoka, Japan, 815-8555
GSK Investigational Site
Fukuoka, Japan, 819-0168
GSK Investigational Site
Hiroshima, Japan, 731-0103
GSK Investigational Site
Hokkaido, Japan, 003-0023
GSK Investigational Site
Hokkaido, Japan, 044-0053
GSK Investigational Site
Hokkaido, Japan, 061-1395
GSK Investigational Site
Hokkaido, Japan, 080-0010
GSK Investigational Site
Hokkaido, Japan, 080-0016
GSK Investigational Site
Ibaraki, Japan, 310-0826
GSK Investigational Site
Ibaraki, Japan, 311-0113
GSK Investigational Site
Kagoshima, Japan, 891-0401
GSK Investigational Site
Kanagawa, Japan, 210-0852
GSK Investigational Site
Kanagawa, Japan, 235-0045
GSK Investigational Site
Kumamoto, Japan, 862-0976
GSK Investigational Site
Kumamoto, Japan, 866-0862
GSK Investigational Site
Miyagi, Japan, 980-0021
GSK Investigational Site
Miyagi, Japan, 985-0852
GSK Investigational Site
Nagasaki, Japan, 856-0831
GSK Investigational Site
Saitama, Japan, 355-0321
GSK Investigational Site
Saitama, Japan, 362-0021
GSK Investigational Site
Tochigi, Japan, 329-0101
GSK Investigational Site
Tochigi, Japan, 329-0433
GSK Investigational Site
Tokyo, Japan, 125-0054
GSK Investigational Site
Tokyo, Japan, 154-0015
GSK Investigational Site
Tokyo, Japan, 177-0041
GSK Investigational Site
Yamagata, Japan, 990-0885

Sponsors and Collaborators

GlaxoSmithKline

Investigators

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Study Director:	GSK Clinical Trials	GlaxoSmithKline

More Information

Additional Information:

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