Clinical trial NCT01098461: Dose Ranging Study of Albiglutide in Japanese Subjects
Official title: A Dose Finding Study of GSK716155 Versus Placebo in the Treatment of Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Keywords: dose-ranging
pharmacokinetics
GSK716155
Japan
albiglutide
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-04-02
Enrollment: 215
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Change From Baseline in HbA1c at Weeks 4, 8, 12, and 16
timeFrame: Baseline; Week 4, Week 8, Week 12, and Week 16
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 4, 8, 12, and 16
timeFrame: Baseline; Week 4, Week 8, Week 12, and Week 16
measure: Change From Baseline in Body Weight at Week 4, 8, 12, and 16
timeFrame: Baseline; Week 4, Week 8, Week 12, and Week 16
measure: Number of Participants Who Achieved Clinically Meaningful HbA1c Response Levels of <6.5% and <7% at Weeks 4, 8, 12, and 16
timeFrame: Week 4, Week 8, Week 12, and Week 16
measure: Mean Clearance of Albiglutide
timeFrame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
measure: Mean Volume of Distribution of Albiglutide
timeFrame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
measure: Mean Absorption Rate of Albiglutide
timeFrame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
measure: Mean Half-maximal Effective Concentration (EC50) of Albiglutide for HbA1c and FPG
timeFrame: Weeks 0, 1, 4, 5, 8, 12, 13, 16, 20, and 24
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Kumamoto
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yamagata
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Seino Y, Inagaki N, Miyahara H, Okuda I, Bush M, Ye J, Holland MC, Johnson S, Lewis E, Nakajima H. A randomized dose-finding study demonstrating the efficacy and tolerability of albiglutide in Japanese patients with type 2 diabetes mellitus. Curr Med Res Opin. 2014 Jun;30(6):1095-106. doi: 10.1185/03007995.2014.896327. Epub 2014 Mar 11.