Dose Ranging Study of Albiglutide in Japanese Subjects

Condition(s) targeted: Diabetes Mellitus, Type 2

Intervention: albiglutide (Biological); placebo (Biological)

Phase: Phase 2

Status: Completed

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

This is a randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging study evaluating the dose response, efficacy and safety of subcutaneously injected GSK716155 (albiglutide) in Japanese subjects with type 2 diabetes mellitus.

Official title: A Dose Finding Study of GSK716155 Versus Placebo in the Treatment of Type 2 Diabetes Mellitus

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

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

Secondary outcome:

Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16

Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16

Change From Baseline in Body Weight at Week 4, 8, 12, and 16

Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16

Mean Clearance of Albiglutide

Mean Volume of Distribution of Albiglutide

Mean Absorption Rate of Albiglutide

Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG

Detailed description: This is a Phase IIb, randomized, double-blind, placebo-controlled, multicenter, 4-parallel-group, dose ranging, superiority study evaluating the dose response, efficacy and safety of weekly and every other week subcutaneously injected GSK716155 (albiglutide) in subjects with type 2 diabetes mellitus.

Minimum age: 20 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subject with a historical diagnosis of type 2 diabetes mellitus who is currently

treated with diet and exercise only or one OAD

- BMI ≥18 kg/m2 and <35 kg/m2 at Screening

- HbA1c between 7. 0% and 10. 0%, inclusive

- Fasting C-peptide ≥0. 8 ng/mL (≥0. 26 nmol/L)

- Female subjects of childbearing potential must be practicing adequate contraception .

- Able and willing to monitor his/her own blood glucose concentrations with a home

glucose monitor.

- Able and willing to provide written informed consent

Exclusion Criteria:

- Diagnosis of type 1 diabetes mellitus

- Uncorrected thyroid dysfunction

- 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

- Clinically significantly cardiovascular and/or cerebrovascular disease including, but

not limited to the following:

- Previous history of stroke or transient ischemic attack

- Active, unstable coronary heart disease within the past six months before

Screening

- Documented myocardial infarction within one year before Screening

- Any cardiac surgery including percutaneous transluminal coronary angioplasty,

coronary stent placement, or coronary artery bypass graft surgery within one year before Screening

- Unstable angina

- Clinically significant arrhythmia or valvular heart disease

- Current heart failure NYHA class II to IV

- Resting systolic pressure >160 mm Hg or diastolic pressure >95 mm Hg at

Screening

- ECG criteria at Screening

- Heart rate: <40 and >110 bpm

- PR interval: <120 and > 210 msec

- QRS interval: <70 and >120 msec

- QTc interval (Bazett): >450 msec or >480 msec with bundle branch block

- Fasting triglyceride level >400 mg/dL at Screening

- AST or ALT >2xULN, ALP and bilirubin >1. 5xULN (except known Gilbert's syndrome and a

fractionated bilirubin that shows conjugated bilirubin <35% of total bilirubin)

- If female, is currently lactating, within 6 weeks post-partum, pregnant, or actively

trying to become pregnant

- Has significant renal disease as manifested by one or more of the following:

- Creatinine clearance at screening <60 mL/min (calculated by Cockcroft-Gault

formula) at Screening

- Known loss of a kidney either by surgical ablation, injury or disease level

- A hemoglobinopathy that may affect determination of HbA1c level

- History of treated diabetic gastroparesis

- History of significant gastrointestinal surgery, including gastric bypass and

banding, or surgeries thought to significantly affect upper gastrointestinal function

- Current ongoing symptomatic biliary disease or history of acute/chronic pancreatitis.

- Lipase and amylase at Screening > ULN

- Severe diabetic neuropathy, preproliferative retinopathy or proliferative

retinopathy, history of ketoacidosis or hyperosmolar coma

- History of cancer, other than squamous cell or basal cell carcinoma of the skin, that

has not been in full remission for at least 3 years before Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed)

- Acute or chronic history of liver disease, positive hepatitis B surface antigen

(HBsAg) or positive hepatitis C testing at Screening

- Current and history of alcohol or substance abuse

- Clinically significant anaemia or any other abnormal haematological profile that is

considered by the investigator to be clinically significant

- Prior use of a GLP-1 analog

- Known allergy to any formulation excipients, or Baker's yeast, or history of drug, or

other allergy which, in the opinion of the responsible study physician, contradicts participation

- History of or family history of medullary carcinoma of the thyroid.

- History of or family history of multiple endocrine neoplasia type 2

- Receipt of any investigational drug within the 12 weeks before Screening

GSK Investigational Site, Aichi 466-0815, Japan

GSK Investigational Site, Ehime 790-0067, Japan

GSK Investigational Site, Fukuoka 810-0001, Japan

GSK Investigational Site, Fukuoka 811-1346, Japan

GSK Investigational Site, Fukuoka 815-8555, Japan

GSK Investigational Site, Fukuoka 819-0168, Japan

GSK Investigational Site, Hiroshima 731-0103, Japan

GSK Investigational Site, Hokkaido 003-0023, Japan

GSK Investigational Site, Hokkaido 044-0053, Japan

GSK Investigational Site, Hokkaido 061-1395, Japan

GSK Investigational Site, Hokkaido 080-0010, Japan

GSK Investigational Site, Hokkaido 080-0016, Japan

GSK Investigational Site, Ibaraki 310-0826, Japan

GSK Investigational Site, Ibaraki 311-0113, Japan

GSK Investigational Site, Kagoshima 891-0401, Japan

GSK Investigational Site, Kanagawa 210-0852, Japan

GSK Investigational Site, Kanagawa 235-0045, Japan

GSK Investigational Site, Kumamoto 866-0862, Japan

GSK Investigational Site, Kumamoto 862-0976, Japan

GSK Investigational Site, Miyagi 980-0021, Japan

GSK Investigational Site, Miyagi 985-0852, Japan

GSK Investigational Site, Nagasaki 856-0831, Japan

GSK Investigational Site, Saitama 362-0021, Japan

GSK Investigational Site, Saitama 355-0321, Japan

GSK Investigational Site, Tochigi 329-0101, Japan

GSK Investigational Site, Tochigi 329-0433, Japan

GSK Investigational Site, Tokyo 125-0054, Japan

GSK Investigational Site, Tokyo 154-0015, Japan

GSK Investigational Site, Tokyo 177-0041, Japan

GSK Investigational Site, Yamagata 990-0885, Japan

Starting date: April 2010
Last updated: May 29, 2014