Diabetes Mellitus
Conditions
Keywords
diabetes, mellitus, metformin
Brief summary
This is a phase 2a, multicenter, randomized, double-blind, placebo-controlled, parallel group, fixed dose study. AMG 151 will be evaluated in subjects with type 2 diabetes treated with metformin for at least 3 months prior to randomization.
Interventions
DRUGAMG 151
Drug: AMG 151 50 mg BID
DRUGPlacebo
Placebo
DRUGMetformin
Subjects will remain on their metformin regimen throughout the study. The metformin dose must be ≥ 850 mg/day for at least 2 months immediately prior to randomization.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 75 years, inclusive * Diagnosis of type 2 diabetes mellitus * HbA1c levels 7.5% to 11.0%, inclusive, at screening * Fasting C-peptide levels ≥ 0.2 nmol/L at screening * BMI ≥ 25 to \< 45 kg/m2 at screening * Treated with metformin monotherapy for at least 3 months prior to randomization; the metformin dose must be ≥ 850 mg daily for at least 2 months immediately prior to randomization * If a subject is being treated for hyperlipidemia or hypertension they should be on stable medication for 30 days before randomization * Subject has provided informed consent.
Exclusion criteria
* History of type 1 diabetes * History of significant weight gain or loss (\> 10%) during the 4 weeks before randomization * Use of any weight loss medication (over the counter or prescription) within 60 days of randomization * Use of any oral or injectable anti-hyperglycemic medication (other than metformin) within 3 months prior to randomization * Use of chronic and/or continuous insulin administration for \> 15 days in an outpatient setting to achieve and maintain glycemic control prior to randomization * Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months * Have had more than 1 episode of severe hypoglycemia within 6 months prior to entry into the study, or currently diagnosed as having hypoglycemia unawareness * Evidence of active infections that can interfere with the study * Presence of clinically significant organ system disease that is not stabilized or may interfere with the study * Currently receiving immunosuppressive therapy * History of positive HIV, chronic hepatitis B or C, or cirrhosis * Have symptomatic congestive heart failure or a history of myocardial infarction, unstable angina, or decompensated congestive heart failure or stroke in the past 6 months prior to screening. * History of gastric surgery, vagotomy, bowel resection or any surgical procedure that might interfere with gastrointestinal motility, pH or absorption * Any finding on the screening ECG that in the opinion of the investigator requires further cardiovascular evaluation * Poorly controlled hypertension defined as diastolic pressure \> 100 mm Hg or systolic pressure \> 160 mm Hg (assessed on two separate occasions during the screening period) * Malignancy (other than resected cutaneous basal or cutaneous squamous cell carcinoma, or treated in situ cervical cancer considered cured) within 5 years of screening visit (if a malignancy occurred \> 5 years ago, subject is eligible with documentation of disease-free state since treatment) * Use of known inhibitors or inducers of CYP3A4 are not permitted 30 days prior to randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the dose-effect relationship of AMG 151 compared to placebo on fasting plasma glucose in subjects with type 2 diabetes treated with metformin | Change in fasting plasma glucose levels from baseline to Day 28 |
Secondary
| Measure | Time frame |
|---|---|
| To assess the effect of AMG 151 on postprandial glucose levels in response to a meal tolerance test | Change in area under the curve from 0-4 hours (AUC0-4hr) glucose after a meal tolerancetest from baseline to Day 28, Change in incremental AUC0-4hr glucose after a meal tolerance test from baseline to Day 28 |
| Adverse events | Incidence of serious adverse events from signing of ICF to Day 42. Incidence of non-serious adverse events from randomization to Day 42. |
Countries
Czechia, Estonia, Poland, Puerto Rico, United States
Outcome results
None listed