Type 2 Diabetes Mellitus MedDRA version: 14.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
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 metformin but who is experiencing inadequate glycemic control. The subject should have received metformin for at least 3 months before Screening; and the subject must have a stable dose of =1500 mg metformin for at least 8 weeks before randomization. Subjects with a documented MTD of 7 contiguous days of any antidiabetic agents other than 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 subjects be on 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 method (condom and occlusive cap plus nonoxynol-9), or oral contraceptives in combination with a second method of contraception (e.g., condom and occlusive cap). Adequate contraception must be practiced for the duration of participation in the study including the 8-week Posttreatment Follow-up Period 11. Able and willing to monitor his or her own blood glucose concentrations with a home glucose monitor 12. No major illness or debility that in the investigator’s opinion prohibits the subject from completing the study 13. Able and wi
Exclusion criteria
Exclusion criteria: 1.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) 2.History of treated diabetic gastroparesis 3.Current ongoing symptomatic biliary disease or history of pancreatitis 4.History of significant gastrointestinal surgery, including gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper gastrointestinal function 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; however, as an example, controlled atrial fibrillation is allowed •Current or history of heart failure (New York Heart Association class III to IV) •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 6.Hemoglobinopathy that may affect determination of HbA1c 7.History of human immunodeficiency virus infection 8.History of total bilirubin >1.5 × ULN, unless the subject has a previously known history of Gilbert’s syndrome and a fractionated bilirubin that shows conjugated bilirubin 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 (Visit 5), the subject is excluded. If the subject meets the aforementioned exclusion criterion for triglycerides, the subjec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 metformin as compared with metformin + sitagliptin, metformin + glimepiride, and metformin + placebo: • HbA1c change from Baseline over time • Other measures of glycemic control, including fasting plasma glucose, 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;Main Objective: The primary objective of the study is to evaluate the efficacy of albiglutide administered in combination with metformin as compared with metformin + sitagliptin, metformin + glimepiride, and metformin + placebo on HbA1c (glycosylated hemoglobin) change from Baseline at Week 104.;Primary end point(s): The primary efficacy endpoint is the change from Baseline in HbA1c at Week 104. | — |
Countries
Germany, Spain, United Kingdom
Outcome results
None listed