Clinical trial NCT01475734: Albiglutide Glucose Clamp Study in Subjects With Type 2 Diabetes
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: glucose clamp
hypoglycemia
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-11-21
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure
timeFrame: Day 4
Secondary outcomes:
measure: Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period
timeFrame: Day 4
measure: Epinephrine Values During the Glucose Clamp Period
timeFrame: Day 4
measure: Norepinephrine Values During the Glucose Clamp Period
timeFrame: Day 4
measure: Growth Hormone Values During the Glucose Clamp Period
timeFrame: Day 4
measure: Insulin Values During the Glucose Clamp Period
timeFrame: Day 4
measure: Cortisol Values During the Glucose Clamp Period
timeFrame: Day 4
measure: C-peptide Values During the Glucose Clamp Period
timeFrame: Day 4
measure: 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)
timeFrame: Day 4
measure: Average Albiglutide Concentration on the Day of the Clamp Procedure
timeFrame: Day 4
measure: Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period
timeFrame: 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)
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: GSK Investigational Site
state: California
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.