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

Phase 1
Completed
Conditions
Type 2 Diabetes (T2D)
Interventions
Drug: Placebo
Registration Number
NCT01088711
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
32
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Healthy PlaceboPlaceboObese healthy participants receive once-weekly placebo by mouth for 4 weeks (Panel A).
T2D PlaceboPlaceboObese participants with T2D receive once-weekly placebo by mouth for 4 weeks (Panel B).
Healthy OmarigliptinOmarigliptinObese healthy participants receive once-weekly omarigliptin 50 mg by mouth for 4 weeks (Panel A).
T2D OmarigliptinOmarigliptinObese participants with T2D receive once-weekly omarigliptin 50 mg by mouth for 4 weeks (Panel B).
Primary Outcome Measures
NameTimeMethod
Number of Participants Withdrawing From Study Therapy Due to an AEUp to Day 22
Number of Participants Experiencing an Adverse Event (AE)Up to Day 36
Secondary Outcome Measures
NameTimeMethod
Percent Inhibition of Dipeptidyl Peptidase-4 (DPP-4) After Day 15168 hours post-dose on 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.

Percent Inhibition of DPP-4 After Day 22168 hours post dose on 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.

WAA Active Glucagon-like Peptide-1 (GLP-1) ConcentrationThrough 4 hours post dose on Day 21

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.

WAA Total GLP-1 ConcentrationThrough 4 hours post dose on Day 21

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.

Plasma Glucose ConcentrationThrough 4 hours post dose on Day 21

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.

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