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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes (T2D)
• Intervention / Treatment: Drug: Omarigliptin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Omarigliptin; Obese healthy participants receive once-weekly omarigliptin 50 mg by mouth for 4 weeks (Panel A).	Drug: Omarigliptin; Once-weekly 50 mg capsule; Other Names: MK-3102
Placebo Comparator: Healthy Placebo; Obese healthy participants receive once-weekly placebo by mouth for 4 weeks (Panel A).	Drug: Placebo; Once-weekly placebo capsule
Experimental: T2D Omarigliptin; Obese participants with T2D receive once-weekly omarigliptin 50 mg by mouth for 4 weeks (Panel B).	Drug: Omarigliptin; Once-weekly 50 mg capsule; Other Names: MK-3102
Placebo Comparator: T2D Placebo; Obese participants with T2D receive once-weekly placebo by mouth for 4 weeks (Panel B).	Drug: Placebo; Once-weekly placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Addy C, Tatosian D, Glasgow XS, Gendrano IN 3rd, Kauh E, Martucci A, Johnson-Levonas AO, Selverian D, Matthews CZ, Gutierrez M, Wagner JA, Aubrey Stoch S. Pharmacokinetic and Pharmacodynamic Effects of Multiple-dose Administration of Omarigliptin, a Once-weekly Dipeptidyl Peptidase-4 Inhibitor, in Obese Participants With and Without Type 2 Diabetes Mellitus. Clin Ther. 2016 Mar;38(3):516-30. doi: 10.1016/j.clinthera.2015.12.020. Epub 2016 Feb 9.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2010
• Primary Completion (Actual): May 11, 2010
• Study Completion (Actual): May 11, 2010

Study Registration Dates

• First Submitted: March 16, 2010
• First Submitted That Met QC Criteria: March 16, 2010
• First Posted (Estimate): March 17, 2010

Study Record Updates

• Last Update Posted (Actual): September 10, 2018
• Last Update Submitted That Met QC Criteria: August 8, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Type 2 diabetes (T2D)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 3102-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis