Evaluation of Omarigliptin (MK-3102) in Obese Participants and in Participants With Type 2 Diabetes (MK-3102-004)

Study Overview
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Brief Summary
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This study will test the safety and tolerability of omarigliptin. It is hypothesized that administration of once-weekly omarigliptin in obese but otherwise healthy participants, and in obese participants with Type 2 diabetes (T2D) will be sufficiently safe and well tolerated to permit continued clinical investigation.

Official Title
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A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK3102 in Obese Subjects and in Patients With Type 2 Diabetes

Conditions
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Type 2 Diabetes (T2D)

Intervention / Treatment
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* Drug: Omarigliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: obese (body mass index [BMI] ≥30 kg/m² and ≤40 kg/m²) male participants and female participants of non-childbearing potential has been diagnosed with T2D (Panel B) is not actively participating in a weight loss program Exclusion Criteria: has a history of clinically-significant disease (other than T2D) has a history of cancer has estimated creatinine clearance ≤60 mL/min is unable to refrain from or anticipates the use of any prescription or non-prescription medication consumes excessive amounts of alcohol or caffeine has participated in a previous omarigliptin study

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Healthy Omarigliptin<br>Obese healthy participants receive once-weekly omarigliptin 50 mg by mouth for 4 weeks (Panel A). | Drug: Omarigliptin<br>* Once-weekly 50 mg capsule<br>* Other names: MK-3102;|
| Placebo Comparator: Healthy Placebo<br>Obese healthy participants receive once-weekly placebo by mouth for 4 weeks (Panel A). | Drug: Placebo<br>* Once-weekly placebo capsule<br>|
| Experimental: T2D Omarigliptin<br>Obese participants with T2D receive once-weekly omarigliptin 50 mg by mouth for 4 weeks (Panel B). | Drug: Omarigliptin<br>* Once-weekly 50 mg capsule<br>* Other names: MK-3102;|
| Placebo Comparator: T2D Placebo<br>Obese participants with T2D receive once-weekly placebo by mouth for 4 weeks (Panel B). | Drug: Placebo<br>* Once-weekly placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing an Adverse Event (AE) |  | Up to Day 36 | 
| Number of Participants Withdrawing From Study Therapy Due to an AE |  | Up to Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Inhibition of Dipeptidyl Peptidase-4 (DPP-4) After Day 15 | Percent DPP-4 inhibition at 168 hours after the Day 15 dose (from baseline [pre-dose on Day 1]) was compared in healthy and T2D participants receiving omarigliptin or placebo. | 168 hours post-dose on Day 15 | 
| Percent Inhibition of DPP-4 After Day 22 | Percent DPP-4 inhibition at 168 hours after the Day 22 dose (from baseline [pre-dose on Day 1]) was compared in healthy and T2D participants receiving omarigliptin or placebo. | 168 hours post dose on Day 22 | 
| WAA Active Glucagon-like Peptide-1 (GLP-1) Concentration | Weighted average augmentation (WAA) active GLP-1 concentration was based on the 0.25, 0.5, 1, 2, and 4 hour timepoints. WAA was calculated as area under the curve (AUC) for the 4-hr post-dose time period (AUC0-4 hrs); this AUC was then divided by the time interval of 4 hours to obtain WAA. Log scale data were then back-transformed to obtain LS means. | Through 4 hours post dose on Day 21 | 
| WAA Total GLP-1 Concentration | WAA total GLP-1 concentration was based on the 0.25, 0.5, 1, 2, and 4 hour timepoints. WAA was calculated as AUC0-4 hrs; this AUC was then divided by the time interval of 4 hours to obtain WAA. Log scale data were then back-transformed to obtain LS means. | Through 4 hours post dose on Day 21 | 
| Plasma Glucose Concentration | Post-prandial glucose concentration is presented as a weighted average of the 0.25, 0.5, 1, 2, and 4 hour post-dose time points. Glucose concentration was calculated as area under the curve (AUC) for the 4-hr post-dose time period (AUC0-4 hrs); this AUC was then divided by the time interval of 4 hours to obtain weighted average glucose concentration. Log scale data were then back-transformed to obtain LS means. | Through 4 hours post dose on Day 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes (T2D)