- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01098461
Dose Ranging Study of Albiglutide in Japanese Subjects
November 29, 2016 updated by: GlaxoSmithKline
A Dose Finding Study of GSK716155 Versus Placebo in the Treatment of Type 2 Diabetes Mellitus
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
215
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Aichi, Japan, 466-0815
- GSK Investigational Site
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Ehime, Japan, 790-0067
- GSK Investigational Site
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Fukuoka, Japan, 810-0001
- GSK Investigational Site
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Fukuoka, Japan, 815-8555
- GSK Investigational Site
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Fukuoka, Japan, 819-0168
- GSK Investigational Site
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Fukuoka, Japan, 811-1346
- GSK Investigational Site
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Hiroshima, Japan, 731-0103
- GSK Investigational Site
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Hokkaido, Japan, 080-0010
- GSK Investigational Site
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Hokkaido, Japan, 080-0016
- GSK Investigational Site
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Hokkaido, Japan, 003-0023
- GSK Investigational Site
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Hokkaido, Japan, 044-0053
- GSK Investigational Site
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Hokkaido, Japan, 061-1395
- GSK Investigational Site
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Ibaraki, Japan, 311-0113
- GSK Investigational Site
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Ibaraki, Japan, 310-0826
- GSK Investigational Site
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Kagoshima, Japan, 891-0401
- GSK Investigational Site
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Kanagawa, Japan, 210-0852
- GSK Investigational Site
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Kanagawa, Japan, 235-0045
- GSK Investigational Site
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Kumamoto, Japan, 862-0976
- GSK Investigational Site
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Kumamoto, Japan, 866-0862
- GSK Investigational Site
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Miyagi, Japan, 980-0021
- GSK Investigational Site
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Miyagi, Japan, 985-0852
- GSK Investigational Site
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Nagasaki, Japan, 856-0831
- GSK Investigational Site
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Saitama, Japan, 355-0321
- GSK Investigational Site
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Saitama, Japan, 362-0021
- GSK Investigational Site
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Tochigi, Japan, 329-0433
- GSK Investigational Site
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Tochigi, Japan, 329-0101
- GSK Investigational Site
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Tokyo, Japan, 125-0054
- GSK Investigational Site
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Tokyo, Japan, 154-0015
- GSK Investigational Site
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Tokyo, Japan, 177-0041
- GSK Investigational Site
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Yamagata, Japan, 990-0885
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: albiglutide 15mg weekly
once weekly subcutaneous injection of albiglutide 15mg
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subcutaneous injection of albiglutide
Other Names:
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Active Comparator: albiglutide 30mg weekly
once weekly subcutaneous injection of albiglutide 30mg
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subcutaneous injection of albiglutide
Other Names:
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Active Comparator: albiglutide 30mg every other week
subcutaneous injection of 30mg albiglutide every other week
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subcutaneous injection of albiglutide
Other Names:
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Placebo Comparator: placebo
once weekly subcutaneous injection of placebo to match albiglutide
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subcutaneous injection of placebo to match albiglutide
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16
Time Frame: Baseline and Week 16
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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.
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Baseline and Week 16
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16
Time Frame: Baseline; Week 4, Week 8, Week 12, and Week 16
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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.
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Baseline; Week 4, Week 8, Week 12, and Week 16
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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
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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.
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Baseline; Week 4, Week 8, Week 12, and Week 16
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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
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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.
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Baseline; Week 4, Week 8, Week 12, and Week 16
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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
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The number of participants who achieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5% and <7%) were assessed.
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Week 4, Week 8, Week 12, and Week 16
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Mean Clearance of Albiglutide
Time Frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
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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.
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Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
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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.
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Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
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Mean Absorption Rate of Albiglutide
Time Frame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
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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.
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Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
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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
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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.
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Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Young MA, Wald JA, Matthews JE, Scott R, Hodge RJ, Zhi H, Reinhardt RR. Clinical pharmacology of albiglutide, a GLP-1 receptor agonist. Postgrad Med. 2014 Nov;126(7):84-97. doi: 10.3810/pgm.2014.11.2836.
- Seino Y, Inagaki N, Miyahara H, Okuda I, Bush M, Ye J, Holland MC, Johnson S, Lewis E, Nakajima H. A randomized dose-finding study demonstrating the efficacy and tolerability of albiglutide in Japanese patients with type 2 diabetes mellitus. Curr Med Res Opin. 2014 Jun;30(6):1095-106. doi: 10.1185/03007995.2014.896327. Epub 2014 Mar 11.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2010
Primary Completion (Actual)
May 1, 2011
Study Completion (Actual)
May 1, 2011
Study Registration Dates
First Submitted
February 12, 2010
First Submitted That Met QC Criteria
April 1, 2010
First Posted (Estimate)
April 2, 2010
Study Record Updates
Last Update Posted (Estimate)
January 13, 2017
Last Update Submitted That Met QC Criteria
November 29, 2016
Last Verified
November 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 110932
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study Data/Documents
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Dataset Specification
Information identifier: 110932Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Annotated Case Report Form
Information identifier: 110932Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Statistical Analysis Plan
Information identifier: 110932Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Individual Participant Data Set
Information identifier: 110932Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Informed Consent Form
Information identifier: 110932Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Clinical Study Report
Information identifier: 110932Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Study Protocol
Information identifier: 110932Information comments: For additional information about this study please refer to the GSK Clinical Study Register
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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