Investigate Effect of AMG 151 on 24-hour Ambulatory Blood Pressure & Glucose Levels in Type 2 Diabetes Mellitus Subjects

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind, placebo-controlled, 2-way crossover study to evaluate the effect of AMG 151 on 24-hour ambulatory blood pressure and glucose levels in subjects with type 2 diabetes mellitus who are on a stable regimen of metformin alone, metformin and a dipeptidyl peptidase-4 inhibitor (DPP4), metformin and a thiazolidinedione (TZD), or metformin, a DPP4, and a TZD for a minimum of 3 months prior to randomization.

Official Title
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A Phase 1, Double-blind, Randomized, 2-Way Crossover, Placebo-controlled Study to Investigate the Effect of AMG 151 on 24-hour Ambulatory Blood Pressure and Glucose Levels in Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subjects with type 2 diabetes mellitus On a stable regimen of metformin alone, metformin and a DPP4, metformin and a TZD, or metformin, a DPP4, and a TZD for a minimum of 3 months prior to randomization Body mass indices > 25 and < 45 kg/m2 Hemoglobin A1c levels ≥ 7.0% and ≤ 11.0% at screening Fasting C-peptide levels ≥ 0.2 nmol/L at screening Subject with a history of hypertension must be on a stable antihypertensive treatment (s) (type of medication, dose, and regimen) for at least 6 weeks prior to the first dose of investigational product Other criteria may apply Exclusion Criteria Subject has type 1 diabetes mellitus or history of type 1 diabetes mellitus Subject has had 2 or more emergency room visits or hospitalizations due to poor glucose control in the 6 months prior to screening Poorly controlled hypertension defined as diastolic pressure ≥ 95 mmHg or systolic ≥ 155 mmHg (confirmed by a repeat assessment) at screening Triglycerides ≥ 400 mg/dL (4.52 mmol/L) at screening Use of any known cytochrome P450 (CYP) inducers within 30 days or 5 half-lives (whichever is longer), prior to receiving the first dose of investigational product. Use of any known inhibitors of CYP3A4/P-glycoprotein within the 14 days or 5 half lives (whichever is longer) prior to receiving the first dose of investigational product Other criteria may apply

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AMG 151<br> | Drug: AMG 151<br>* Eligible subjects will be randomly assigned (1:1) to receive AMG 151 and matching placebo in 1 of 2 sequences over 2 treatment periods.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Eligible subjects will be randomly assigned (1:1) to receive AMG 151 and matching placebo in 1 of 2 sequences over 2 treatment periods.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 24-hour systolic blood pressure |  | After 14 days of AMG 151 or placebo treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean 24-hour diastolic blood pressure |  | After 14 days of AMG 151 or placebo treatment | 
| Mean 24-hour heart rate |  | After 14 days of AMG 151 or placebo treatment | 
| 24-hour concentration time profile of glucose level from continuous glucose monitoring |  | Day 1 and day 14 of each period | 
| Fasting plasma glucose and fructosamine |  | After 13 days of AMG 151 or placebo treatment | 
| Plasma glucose 2 hours after time 0 of mixed meal tolerance test |  | After 13 days of AMG 151 or placebo treatment | 
| 4-hour concentration time profile of glucose after the mixed meal tolerance test |  | After 13 days of AMG 151 or placebo treatment | 
| Safety end points will include the incidence of treatment emergent adverse events. |  | Up to 2 Months | 
| Serum AMG 151 concentration |  | Up to 2 Months | 
| Safety end points will include laboratory safety tests. |  | Up to 2 Months. | 
| Safety end points will include vital signs. |  | Up to 2 Months | 
| Safety end points will include ECGs. |  | Up to 2 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ambulatory blood pressure, Type 2 diabetes