- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01475734
Albiglutide Glucose Clamp Study in Subjects With Type 2 Diabetes
November 20, 2016 updated by: GlaxoSmithKline
A Single-site, Randomized, Double-blind, Placebo-controlled, Parallel-group, Stepped Glucose Clamp Study to Assess the Effects of Albiglutide on Counter-regulatory Hormone Responses and Recovery From Hypoglycemia in Subjects With Type 2 Diabetes Mellitus.
This is a stepped glucose clamp study designed to investigate the effect of treatment with albiglutide on counter-regulatory hormone responses and recovery from hypoglycemia in subjects with Type 2 diabetes mellitus.
A single dose of albiglutide or placebo will be given prior to a stepped hyper- and hypoglycemic clamp.
The goal of this study is to demonstrate that albiglutide increases insulin secretion and decreases glucagon levels in a glucose-dependent manner.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is a Phase II, single-site, randomized, double-blind, parallel-group, placebo-controlled, stepped glucose clamp study designed to investigate the effect of treatment with albiglutide on counter-regulatory hormone responses and recovery from hypoglycemia in subjects with Type 2 diabetes mellitus.
A single dose of albiglutide or placebo will be given 3 days before employing a stepped hyper- and hypoglycemic clamp.
The goal of this study is to demonstrate that albiglutide increases insulin secretion and decreases glucagon levels in a glucose-dependent manner.
In particular, this study is being conducted to ensure that albiglutide does not impair counter-regulatory responses during hypoglycemia.
Study Type
Interventional
Enrollment (Actual)
44
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
-
-
California
-
Chula Vista, California, United States, 91911
- GSK Investigational Site
-
-
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
18 years to 60 years (ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Historical diagnosis of type 2 diabetes mellitus for at least 6 months and less than 10 years before Screening
- HbA1c <10% at Screening for subjects who do not require washout of existing OAD or <9% at Screening for subjects who do require washout from existing OAD
- Body mass index in range 28 kg/m2 to40 kg/m2
Exclusion Criteria:
- History of pancreatitis or current ongoing symptomatic biliary disease or pancreatitis
- History of significant gastrointestinal surgery,
- History of significant cardiovascular disease
- History of a seizure disorder
- Documented hypertension or hypotension
- Use of oral antidiabetic agents, except for metformin, within 14 days before investigational product administration.
- Current hepatic disease or abnormal liver function tests
- Positive test result for hepatitis B, hepatitis C, or human immunodeficiency virus infection 1 or 2
- History of regular alcohol consumption (exceeding 7 drinks/week for women or 14 drinks/week for men)
- Female subject is pregnant (confirmed by laboratory testing), lactating, or less than 6 weeks postpartum
- Known allergy to any GLP-1 analog or excipients of albiglutide, Baker's yeast, or insulin
- History of type 1 diabetes,
- Prior exposure to GLP-1 agents, including albiglutide
- Blood donation over 500 mL within 8 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
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: albiglutide
single dose of albiglutide
|
subcutaneous injection
|
Placebo Comparator: placebo
single dose of placebo
|
subcutaneous injection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure
Time Frame: Day 4
|
Plasma glucagon levels were measured for the estimation of glucagon secretion during the hypoglycemic periods.
Glucagon response was measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min).
Repeated-measures analysis of variance was performed on non-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
Values below the lower limit of quantification (0.03780 nmol/L) were set to the quantification limit for summary.
|
Day 4
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period
Time Frame: Day 4
|
The insulin secretion rate (ISR) was estimated by the deconvolution of peripheral C-peptide concentrations using a 2-compartment model that utilizes population C-peptide kinetic parameters.
ISR was measured at 1 hr, 1 hr 15 min, 1 hr 45 min, 2 hr, 2 hr 45 min, 3 hr, 3 hr 30 min, 3 hr 45 min, 4 hr 15 min, and 4 hr 30 min.
Repeated-measures analysis of variance was performed on insulin secretion rate using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
|
Day 4
|
Epinephrine Values During the Glucose Clamp Period
Time Frame: Day 4
|
Epinephrine levels were measured at all stages of glycemia during the glucose clamp period.
Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min).
Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
Values below the lower limit of quantification were set to the quantification limit for summary.
|
Day 4
|
Norepinephrine Values During the Glucose Clamp Period
Time Frame: Day 4
|
Norepinephrine levels were measured at all stages of glycemia during the glucose clamp period.
Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min).
Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
Values below the lower limit of quantification were set to the quantification limit for summary.
|
Day 4
|
Growth Hormone Values During the Glucose Clamp Period
Time Frame: Day 4
|
Growth hormone levels were measured at all stages of glycemia during the glucose clamp period.
Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min).
Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
Values below the lower limit of quantification were set to the quantification limit for summary.
|
Day 4
|
Insulin Values During the Glucose Clamp Period
Time Frame: Day 4
|
Insulin levels were measured at all stages of glycemia during the glucose clamp period.
Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min).
Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
Values below the lower limit of quantification were set to the quantification limit for summary.
|
Day 4
|
Cortisol Values During the Glucose Clamp Period
Time Frame: Day 4
|
Cortisol levels were measured at all stages of glycemia during the glucose clamp period.
Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min).
Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
Values below the lower limit of quantification were set to the quantification limit for summary.
|
Day 4
|
C-peptide Values During the Glucose Clamp Period
Time Frame: Day 4
|
C-peptide levels were measured at all stages of glycemia during the glucose clamp period.
Epinephrine levels were measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour [hr], 1hr, 1 hr 15 minutes [min]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min).
Repeated-measures analysis of variance was performed on log-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect.
Values below the lower limit of quantification were set to the quantification limit for summary.
|
Day 4
|
Recovery Time of Plasma Glucose Levels to >=3.9 mmol/L (>=70 mg/dL) From the Hypoglycemic Clamp Level of 2.8 Nmol/L (50.4 mg/dL)
Time Frame: Day 4
|
The effect of albiglutide and placebo on the recovery time of plasma glucose levels to >=3.9 mmol/L (7>=0 mg/dL) from the hypoglycemic clamp level of 2.8 nmol/L (50.4 mg/dL) was calculated as the time in minutes between switching off of the insulin infusion and reaching the level of >=3.9 mmol/L (>=70 mg/dL).
Censored values were censored at 70 minutes.
The median and 95% confidence interval data are obtained from Kaplan-Meier estimates.
|
Day 4
|
Average Albiglutide Concentration on the Day of the Clamp Procedure
Time Frame: Day 4
|
Plasma samples were taken from participants at two time points on Day 4 (at 0 hours and 4 hours and 45 minutes post-dose) of Week 1 of the study for albiglutide study drug level analyses.
The average concentration for each participant was calculated as the mean of the concentrations at 0 hours and 4 hours 45 minutes.
The clamp procedure is a glucose-controlled insulin infusion system.
Variable infusions of glucose are administered to achieve various glucose target levels.
It is a way of quantifying insulin secretion and resistance.
|
Day 4
|
Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period
Time Frame: From the time the participant consented to participate in the study through the end of the study, or the final follow-up visit for participants who discontinued active participation in the study (up to 8 study weeks)
|
Treatment-emergent AEs are defined as those with an onset on or after study drug administration.
An AE is defined as any untoward medical occurrence in a participant or 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, or is a congenital anomaly/birth defect.
|
From the time the participant consented to participate in the study through the end of the study, or the final follow-up visit for participants who discontinued active participation in the study (up to 8 study weeks)
|
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.
- Hompesch M, Jones-Leone A, Carr MC, Matthews J, Zhi H, Young M, Morrow L, Reinhardt RR. Albiglutide does not impair the counter-regulatory hormone response to hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose clamp study in subjects with type 2 diabetes mellitus. Diabetes Obes Metab. 2015 Jan;17(1):82-90. doi: 10.1111/dom.12398. Epub 2014 Oct 26.
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
December 1, 2011
Primary Completion (Actual)
July 1, 2012
Study Completion (Actual)
July 1, 2012
Study Registration Dates
First Submitted
November 17, 2011
First Submitted That Met QC Criteria
November 17, 2011
First Posted (Estimate)
November 21, 2011
Study Record Updates
Last Update Posted (Estimate)
January 11, 2017
Last Update Submitted That Met QC Criteria
November 20, 2016
Last Verified
November 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 108372
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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Study Protocol
Information identifier: 108372Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Statistical Analysis Plan
Information identifier: 108372Information 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: 108372Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Informed Consent Form
Information identifier: 108372Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Clinical Study Report
Information identifier: 108372Information 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: 108372Information comments: For additional information about this study please refer to the GSK Clinical Study Register
-
Dataset Specification
Information identifier: 108372Information 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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