Dose Ranging Study of Albiglutide in Japanese Subjects

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Diabetes Mellitus, Type 2

Treatments: Biological: placebo; Biological: albiglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01098461

110932

Details and patient eligibility

About

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.

Full 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.

Enrollment: 215 patients

Sex: All

Ages: 20 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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215 participants in 4 patient groups, including a placebo group

albiglutide 15mg weekly

Active Comparator group

Description:

once weekly subcutaneous injection of albiglutide 15mg

Treatment:

Biological: albiglutide

albiglutide 30mg weekly

Active Comparator group

Description:

once weekly subcutaneous injection of albiglutide 30mg

Treatment:

Biological: albiglutide

albiglutide 30mg every other week

Active Comparator group

Description:

subcutaneous injection of 30mg albiglutide every other week

Treatment:

Biological: albiglutide

placebo

Placebo Comparator group

Description:

once weekly subcutaneous injection of placebo to match albiglutide

Treatment:

Biological: placebo