Albiglutide Glucose Clamp Study in Subjects With Type 2 Diabetes

NCT01475734 | Completed Phase 2 Results DMC

• 1 other identifier: 108372
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

glucose clamp; hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure

  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 Outcomes (10)

• Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period

  Day 4

• Epinephrine Values During the Glucose Clamp Period

  Day 4

• Norepinephrine Values During the Glucose Clamp Period

  Day 4

• Growth Hormone Values During the Glucose Clamp Period

  Day 4

• Insulin Values During the Glucose Clamp Period

  Day 4

Study Arms (2)

albiglutide

ACTIVE COMPARATOR

single dose of albiglutide

Biological: albiglutide

placebo

PLACEBO COMPARATOR

single dose of placebo

Biological: placebo

Interventions

albiglutide BIOLOGICAL

subcutaneous injection

albiglutide

placebo BIOLOGICAL

subcutaneous injection

placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Chula Vista, California, 91911, United States

Location

Related Publications (2)

• 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.

  PMID: 25387217 DERIVED

• 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.

  PMID: 25263215 DERIVED

Related Links

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

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypoglycemia

Interventions

rGLP-1 protein

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2011
• First Posted: November 21, 2011
• Study Start: December 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: January 11, 2017
• Results First Posted: May 16, 2014

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

US (1)