A 16-Week, Parallel-Group, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of Multiple Doses and Multiple Treatment Regimens of GSK716155, With Byetta as an Open Label Active Reference, in Subjects With Type 2 Diabetes Mellitus

GlaxoSmithKline1 site in 1 country361 target enrollmentApril 2007

ConditionsDiabetes Mellitus, Type 2

DrugsAlbiglutide (GSK716155) or exenatide

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Diabetes Mellitus, Type 2
Sponsor: GlaxoSmithKline
Enrollment: 361
Locations: 1
Primary Endpoint: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This study is a placebo-controlled study in patients with Type 2 Diabetes Mellitus who are either taking no diabetes medication or who are taking metformin only. This study will investigate the safety, tolerability, and efficacy of Albiglutide (GSK716155) and will measure the levels of Albiglutide (GSK716155) in the bloodstream when it is given for 16 weeks. As a comparison, some subjects will receive exenatide instead of Albiglutide (GSK716155). The study will involve weekly visits for 17 weeks,and less frequent follow-up visits for an additional 10 weeks. Assessments include repeat blood sampling and monitoring of any side effects.

Detailed Description

A 16-week, parallel-group, double-blind, randomized, placebo-controlled, multicenter, dose-ranging study to evaluate the efficacy, safety and tolerability of multiple doses and multiple treatment regimens of Albiglutide (GSK716155) with Byetta as an open-label active reference, in subjects with Type 2 Diabetes Mellitus.

Registry

clinicaltrials.gov

Start Date

April 2007

End Date

May 2008

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Has type 2 diabetes mellitus as defined by the criteria of the American Diabetes Association and recognized by World Health Organization Expert Committee on the Diagnosis and Classification of Diabetes Mellitus \[American Diabetes Association, 2004a\] at least three months preceding screening
•Has concurrent type 2 diabetes mellitus therapy: Must be diet and exercise treated; must not have taken antidiabetic medication for at least three months prior to prescreening or Monotherapy with metformin, with a history of a stable dose for at least three months before prescreening (not taking more than one oral antidiabetic agent)
•Has HbA1c level at screening ≥7 and ≤10%
•Is male or female 18 to 75 years of age, inclusive, at screening
•Has body mass index ≥20 and ≤40 kg/m²
•If subject is a smoker, must be able to abstain while in clinic at each visit
•If female, is eligible to enter and participate throughout the study, including the follow-up period: 1) If of nonchildbearing potential (i.e. physiologically incapable of becoming pregnant {tubal ligation}, including any female who is postmenopausal \[\>1 year without menstrual period\]); or, 2) If of childbearing potential, has negative pregnancy tests at screening (serum) and at baseline (urine) and: 3) Has a male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or 4) Uses double-barrier methods of contraception; condoms (with spermicide) and intrauterine devices are acceptable, or 5) Uses hormonal contraceptives (oral, depots, patches, etc) with double-barrier methods of contraception as outlined above, or, 6) Abstains from sexual intercourse, or 7) Is with a same-sex partner and does not participate in bisexual activities where there is any risk of pregnancy
•Signs and dates informed consent before any study-related procedures are performed

Exclusion Criteria

•Has metabolic disease including but not limited to: 1) Diagnosis of type 1 diabetes mellitus, 2) Uncorrected thyroid dysfunction (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least three months prior to screening, and who have a screening thyroid-stimulating hormone within the limits of normal may participate)
•Has qualitative changes in lifestyle that, in the opinion of the investigator, would affect the subject's weight or disease status
•Had 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
•Has clinically significant cardiovascular and/or cerebrovascular disease including, but not limited to: 1) Previous history of stroke or transient ischemic attack, 2) Active, unstable coronary heart disease within the past six months, 3) Documented myocardial infarction within a year prior to screening 4) Any cardiac surgery including percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery within a year prior to screening 5) Unstable angina 6) Clinically significant arrhythmia or valvular heart disease within the past year 7) Congestive heart failure with New York Heart Association Class II to Class IV symptoms. Class I is acceptable. 8) Untreated hypertension, with systolic pressure greater than 160mm Hg and/or diastolic pressure greater than 95mm Hg. 9) ECG exclusion criteria: Heart rate is \<40 and \>110 beats per minute, PR Interval is \<120 and \>210msec, QRS duration is \<70 and \>120msec, QTc interval (Bazett) is \>450msec or \>480msec with bundle branch block
•Has fasting serum triglycerides ≥800mg/dL or 9mmol/L at screening (Visit 2). Subjects receiving lipid-lowering therapy must have been on the same dose of therapy for the past three months. Fasting is defined as no food/drink for at least eight hours prior to sampling
•If female, is currently lactating, pregnant, or actively trying to become pregnant
•Has significant renal disease as manifested by one or more of the following: 1) Creatinine clearance \<60mL/min. (estimated from serum creatinine and demographic data using the modification of diet in renal disease calculation; refer to the SPM/ISFM), 2) Urine albumin excretion ≥500 µg/mL on a urine spot check, 3) Known loss of a kidney either by surgical ablation, injury, or disease
•Has history of significant comorbid diseases active within the last six months (e.g., gastrointestinal disease)
•Has history of pancreatitis within five years prior to randomization
•Has a documented history of chronic or advanced hepatobiliary disease including a history of, or positive laboratory results for, hepatitis at screening (Visit 2), and/or clinically significant hepatic enzyme elevation including: 1) Any two of the following enzymes greater than 1.5 times the upper limit of normal (ULN) value: - alanine aminotransferase (ALT), - aspartate aminotransferase (AST), - alkaline phosphatase (ALP), 2) Any one of the above enzymes two times greater than the ULN value AND total or direct bilirubin \>1.5 times the ULN

Outcomes

Primary Outcomes

Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16

Time Frame: Baseline and Week 16

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 in HbA1c was calculated as the value at Week 16 minus the value at Baseline. Based on ANCOVA: Change = treatment + Baseline HbA1c + prior therapy + gender + region. The last observation carried forward (LOCF) method was used to impute missing data, in which the last valid observation recorded on treatment (scheduled or unscheduled) was used to impute the missing measurement. For participants who had missing observations before their last observation on treatment, the closest previous non-missing on-treatment observation was carried forward to missing visits. If a participant had missing observation(s) immediately after Baseline, the Baseline observation was not carried forward and was left as missing.

Secondary Outcomes

Change From Baseline in Waist Circumference at Week 16(Baseline and Week 16)
Change From Baseline in Body Weight at Week 16(Baseline and Week 16)
Percent Change From Baseline in Body Weight at Week 16(Baseline and Week 16)
Mean Absorption Rate of Albiglutide(Weeks 0, 4, 5, 7, 8, 9, 12, 15, 16, 17 18, 20, 23, and 27)
Change From Baseline in HbA1c at Weeks 4, 5, 7, 8, 9, 12, 15, and 16(Baseline and Weeks 4, 5, 7, 8, 9, 12, 15, and 16)
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 5, 7, 8, 9, 12, 15, and 16(Baseline and Weeks 4, 5, 7, 8, 9, 12, 15, and 16)
Change From Baseline in Fasting Glucagon at Weeks 5, 8, 12, and 16(Baseline and Weeks 5, 8, 12, and 16)
Change From Baseline in Triglycerides, Free Fatty Acids, Total Cholesterol, Low-density Lipoprotein Cholesterol, and High-density Lipoprotein Cholesterol at Weeks 5, 8, 12, and 16(Baseline and Weeks 5, 8, 12, and 16)
Change From Baseline in Functional Living Index - Emesis (FLIE) Scores at Week 16(Baseline and Week 16)
Number of Participants Who Achieved Target Values for HbA1c <6.5% and >=6.5% to <7% at Weeks 4, 5, 7, 8, 9, 12, 15, and 16(Weeks (W) 4, 5, 7, 8, 9, 12, 15, and 16)
Change From Baseline in Fasting Fructosamine at Weeks 5, 8, 12, and 16(Baseline and Weeks 5, 8, 12, and 16)
Mean Clearance of Albiglutide(Weeks 0, 4, 5, 7, 8, 9, 12, 15, 16, 17 18, 20, 23, and 27)
Mean Volume of Distribution of Albiglutide(Weeks 0, 4, 5, 7, 8, 9, 12, 15, 16, 17 18, 20, 23, and 27)
Number of Participants With the Indicated Response to Questions on the Hunger, Craving, and Fullness Questionnaire (HCFQ) at Week 16(Week 16)
Change From Baseline in Fasting C-peptide at Weeks 5, 8, 12, and 16(Baseline and Weeks 5, 8, 12, and 16)
Change From Baseline in Fasting Insulin at Weeks 5, 8, 12, and 16(Baseline and Weeks 5, 8, 12, and 16)
Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG(Weeks 0, 4, 5, 7, 8, 9, 12, 15, 16, 17 18, 20, 23, and 27)