AMG 151 Amgen Protocol Number 20100761

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Explore Dose Effect and Frequency of Administration of AMG 151 in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: AMG 151
* Drug: Placebo
* Drug: Metformin
* Drug: AMG 151
* Drug: AMG 151
* Drug: AMG 151
* Drug: AMG 151
* Drug: AMG 151


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AMG 151 - Arm 1<br>AMG 151 - Arm 1 | Drug: AMG 151<br>* Drug: AMG 151 50 mg BID<br>Drug: Metformin<br>* 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.<br>|
| Active Comparator: AMG 151 - Arm 2<br>AMG 151 - Arm 2 | Drug: Metformin<br>* 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.<br>Drug: AMG 151<br>* Drug: AMG 151 100 mg BID<br>|
| Active Comparator: AMG 151 - Arm 3<br>AMG 151 - Arm 3 | Drug: Metformin<br>* 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.<br>Drug: AMG 151<br>* Drug: AMG 151 200 mg BID<br>|
| Active Comparator: AMG 151 - Arm 4<br>AMG 151 - Arm 4 | Drug: Metformin<br>* 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.<br>Drug: AMG 151<br>* Drug: AMG 151 100 mg QD<br>|
| Active Comparator: AMG 151 - Arm 5<br>AMG 151 - Arm 5 | Drug: Metformin<br>* 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.<br>Drug: AMG 151<br>* Drug: AMG 151 200 mg QD<br>|
| Active Comparator: AMG 151 - Arm 6<br>AMG 151 - Arm 6 | Drug: Metformin<br>* 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.<br>Drug: AMG 151<br>* Drug: AMG 151 400 mg QD<br>|
| Placebo Comparator: Placebo Arm<br>AMG 151 Placebo Arm | Drug: Placebo<br>* Placebo<br>Drug: Metformin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, mellitus, metformin