Safety and Efficacy Study of Albiglutide in Type 2 Diabetes

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00849017
First received: February 19, 2009
Last updated: May 29, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine whether albiglutide is effective in the treament of patients with type 2 diabetes.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Biological: albiglutide
Biological: albiglutide uptitration
Biological: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Determine the Efficacy and Safety of Two Dose Levels of Albiglutide Compared With Placebo in Subjects With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Glycated hemoglobin (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 BL HbA1c is defined as the last non-missing value before the start of treatment. Change from BL was calculated as the value at Week 52 minus the value at BL. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, history of prior myocardial infarction (yes versus no), and age category (<65 years versus ≥65 years) as factors and Baseline HbA1c as a continuous covariate. The last observation carried forward (LOCF) method was used to impute missing post-BL HbA1c values; the last non-missing post-BL on-treatment measurement was used to impute the missing measurement. HbA1c values obtained after hyperglycemic rescue were treated as missing and were replaced with pre-rescue values.


Secondary Outcome Measures:
  • Change From Baseline in HbA1c at Weeks 104 and 156 [ Time Frame: Baseline and Weeks 104 and 156 ] [ Designated as safety issue: No ]
    HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Baseline HbA1c value is defined as the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed HbA1c values, excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

  • Time to Hyperglycemia Rescue [ Time Frame: From the start of study medication until the end of the treatment (up to Week 156) ] [ Designated as safety issue: No ]
    Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: FPG >=280 milligrams/deciliter (mg/dL) between >=Week 2 and <Week 4; FPG >=250 mg/dL between >=Week 4 and <Week 12; HbA1c >=8.5% and a <=0.5% reduction from Baseline between >=Week 12 and <Week 24; HbA1c >=8.5% between >=Week 24 and <Week 48; HbA1c >=8.0% between >= Week 48 and <Week 156. Participants could have been rescued at any time on or after Week 2. Time to hyperglycemia rescue is defined as the time between the date of the first dose of study medication and the date of hyperglycemia rescue plus 1 day, or the time between the date of the first dose of study medication and the date of the last visit during the active treatment period plus 1 day for participants not requiring rescue. This time was divided by 7 to express the result in weeks.

  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    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. FPG values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on ANCOVA: change = treatment + Baseline weight + prior myocardial infarction history + age category + region + current antidiabetic therapy.

  • Change From Baseline in Fasting Plasma Glucose (FPG) at Week 156 [ Time Frame: Baseline and Week 156 ] [ Designated as safety issue: No ]
    The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline FPG minus the Baseline FPG.

  • Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
    The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 52) were assessed.

  • Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5%, <7%, and <7.5% at Week 156 [ Time Frame: Week 156 ] [ Designated as safety issue: No ]
    The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of <6.5%, <7%, and <7.5% at Week 156) were assessed.

  • Change From Baseline in Body Weight at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    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. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with prerescue values. Based on ANCOVA: change = treatment + Baseline weight + prior myocardial infarction history + age category + region + current antidiabetic therapy.

  • Change From Baseline in Body Weight at Week 156 [ Time Frame: Baseline and Week 156 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Postprandial Blood Glucose Profile Parameter-4 Hour C-peptide AUC [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameter analyzed was 4 hour c-peptide AUC. The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

  • Change From Baseline in Postprandial Blood Glucose Profile Parameter- 4 Hour Blood Glucose AUC [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameter analyzed was: 4 hour blood glucose area under urve AUC The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

  • Change From Baseline in Postprandial Blood Glucose Profile Parameters-4 Hour Insulin AUC and 4 Hour Proinsulin AUC [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: No ]
    Changes from Baseline at Week 52 in postprandial parameters after a mixed-meal (MM) tolerance test were analyzed. Post prandial blood glucose parameters analyzed were: 4-hour insulin AUC (4 hr Ins AUC), and 4-hour proinsulin AUC (4 hr pro-Ins AUC). The AUC was determined using the trapezoidal method using measurements until 4 hours following the meal. The standardized AUC is the total AUC divided by elapsed time. Those parameters were analyzed analogous to the primary endpoint using an ANCOVA model with treatment group as a factor, and corresponding Baseline postprandial profile as a continuous covariate. This analysis used observed values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

  • Albiglutide Plasma Concentration at Weeks 8 and 24 [ Time Frame: Weeks 8 and 24 ] [ Designated as safety issue: No ]
    Albiglutide plasma concentration data was analyzed at Week 8 pre-dose, Week 8 post dose, Week 24 pre-dose and Week 24 post-dose. All participants who received albiglutide were initiated on a 30mg weekly dosing regimen; however, beginning at Week 12, participants in the albiglutide 50 mg treatment group were uptitrated to receive albiglutide 50 mg for the remainder of the study.


Enrollment: 309
Study Start Date: January 2009
Study Completion Date: January 2013
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: albiglutide
albiglutide weekly injection
Biological: albiglutide
albiglutide weekly injection
Placebo Comparator: placebo
albiglutide matching placebo
Biological: placebo
matching albiglutide placebo weekly injection
Experimental: albiglutide up-titration
albiglutide weekly injection uptitration at week 12
Biological: albiglutide uptitration
albiglutide uptitration at week 12

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • type 2 diabetes
  • BMI 20-45kg/m2 inclusive

Exclusion Criteria:

  • females who are pregnant, lactating, or <6 weeks post-partum
  • CHF NYHA class III-IV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00849017

  Show 262 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00849017     History of Changes
Other Study ID Numbers: 112756
Study First Received: February 19, 2009
Results First Received: April 24, 2014
Last Updated: May 29, 2014
Health Authority: South Africa: Medicines Control Council
Mexico: Ministry of Health
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
placebo
albiglutide
monotherapy
diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Albiglutide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Incretins
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014