Type 2 Diabetes Mellitus MedDRA version: 9.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus
Conditions
Interventions
Product Name: Albiglutide
Product Code: GSK716155
Pharmaceutical Form: Powder and solvent for solution for injection
Current Sponsor code: GSK716155
Sponsors
GlaxoSmithKline LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrollment in the study must meet all of the following criteria: 1. Male or female, 18 years of age or older, with a historical diagnosis of type 2 diabetes mellitus who is currently treated with pioglitazone (with or without metformin), but who is experiencing inadequate glycemic control. The subject should have received pioglitazone (with or without metformin) for at least 3 months before Screening; and stable doses for at least 8 weeks before randomization. Subjects receiving pioglitazone as part of their antidiabetic therapy should be on a stable dose of at least 30 mg daily, unless there is documentation that a lower dose (i.e., 15 mg) is the subject’s MTD. Subjects receiving metformin must have a stable dose of =1500 mg of metformin. Subjects with a documented MTD of 7 contiguous days of any antidiabetic agents other than pioglitazone (with or without metformin) within the 3 months before Screening 2. BMI =20 kg/m2 and =45 kg/m2 3. Fasting C-peptide =0.8 ng/mL (=0.26 nmol/L) 4. HbA1c between 7.0% and 10.0%, inclusive, at Visit 5 (Week -1). The HbA1c value may be checked up to 4 times, and if the average of these determinations meets the criterion, the subject may be randomly assigned to treatment 5. For the regular use of other medications (does not include medications excluded by the protocol [see Section 5.6.2, for example, weight loss medications are excluded]), it is preferred that the subjects are receiving a stable dose for at least 4 weeks before Screening; however, as necessary during the Run-in/Stabilization Period and the Treatment Period, prescription or over-the-counter medications are allowed and may be adjusted by the investigator to optimize treatment (e.g., increase or decrease of medication to treat blood pressure or hyperlipidemia in accordance with accepted local medical practice and relevant guidance documents) 6. Use of oral or systemically injected glucocorticoids is generally not allowed within the 3 months before randomization; however, short courses of oral steroids (single dose or multiple doses for up to 2 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra-articular, and topical corticosteroids are allowed 7. Hemoglobin =11 g/dL (=110 g/L) for male subjects and =10 g/dL (=100 g/L) for female subjects 8. Creatinine clearance >60 mL/min (calculated using the Cockcroft-Gault formula) 9. Thyroid-stimulating hormone level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., T4, T3, thyroid-binding globulin) 10. Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception. Methods of adequate contraception include the following: abstinence, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device or intrauterine system, male partner sterilization (vasectomy with documentation of azoospermia) before the female subjects entry into the study and this male partner is the sole partner for that subject, double-barrier m
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 5. Recent (as defined below) clinically significant cardiovascular and/or cerebrovascular disease including, but not limited to, the following: • Previous history of stroke or transient ischemic attack within 1 month before Screening. However, subjects who are deemed clinically stable by the investigator may be enrolled 1 month after the cerebrovascular event • Acute coronary syndrome, which includes the following: • Documented MI within the 2 months before Screening and during the period up until receiving the first dose of study medication • Any cardiac surgery including percutaneous transluminal coronary angioplasty, coronary stent placement, or coronary artery bypass graft surgery within the 2 months before Screening and during the period up until receiving the first dose of study medication • Unstable angina not responsive to nitroglycerin within the 2 months before Screening and during the period up until receiving the first dose of study medication • Unstable cardiac rhythm; controlled atrial fibrillation is allowed • Current or history of heart failure (New York Heart Association class I to IV). Note: The starting dose of pioglitazone in this protocol is 30 mg daily. Investigators must consult the approved product labeling for pioglitazone in their country to determine a subject’s eligibility to participate in this study. • Resting systolic pressure is >160 mm Hg and/or diastolic pressure >100 mm Hg. If the subject’s systolic blood pressure > 160 mm Hg or the subject’s diastolic blood pressure is >100 mm Hg at Screening, the blood pressure reading may be repeated at 5-minute intervals for a total of 3 determinations. If the average of the systolic or diastolic pressure readings still does not meet the criteria, the subject can be treated and rescreened. It is preferred that subjects be on a stable dose of medication for at least 4 weeks before being rescreened; however, when stable, they may be rescreened at the discretion of the investigator Should a subject not meet this criterion on Visit 6 (first dose of study medication following the randomization visit), the subject may continue in the study at the discretion of the investigator with the understanding that the subject’s hypertension will be monitored and treated in accordance with accepted local medical practice and relevant guidance documents. • Mean QTc interval (Fridericia) >470 ms confirmed by a central reader at Screening 9. ALT 3 or aspartate aminotransferase (AST) >2.5 × ULN 10. Fasting triglyceride level >850 mg/dL at Screening or Week -1 (Visit 5). If the subject’s triglyceride level is >500 mg/dL at Screening and Week -1, the subject is excluded. If the subject meets the aforementioned exclusion criterion for triglycerides, the subject can be treated and rescreened. Treated subjects must be on a stable dose of medication for at least 4 weeks before being rescreened4 11. Acute symptomatic (within 3 months before Screening) infection with hepatitis B; however, subjects with past or chronic hepatitis B or hepatitis C are allowed provided the requirements for ALT, AST, and total bilirubi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate the efficacy of albiglutide administered in combination with pioglitazone (with or without metformin) as compared with pioglitazone (with or without metformin) on HbA1c change from Baseline at Week 52.; Secondary Objective: Secondary efficacy objectives at time points to be specified in the statistical analysis plan include the following evaluations of treatment with albiglutide administered in combination with pioglitazone (with or without metformin) as compared with pioglitazone (with or without metformin): • HbA1c change from Baseline over time • Other measures of glycemic control, including fasting plasma glucose (FPG), time to hyperglycemia rescue, and incidence of clinically meaningful levels of response in HbA1c (i.e., the proportion of subjects at or below treatment goal of 6.5%, 7.0%, and 7.5%) • Changes from Baseline in body weight ;Primary end point(s): The primary efficacy endpoint is the change from Baseline in HbA1c at Week 52. | — |
Countries
Spain, United Kingdom
Outcome results
None listed