A Dose-Range Finding Study in Participants With Type 2 Diabetes (MK-3102-006)

NCT ID: NCT01217073

Last Updated: 2018-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 685 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-08
• Study Completion Date: 2013-04-01

Brief Summary

The purpose of this study is to assess the hypothesis that treatment with study medication (omarigliptin; MK-3102) provides greater reduction in A1C Hemoglobin (a marker of diabetic severity) compared with placebo, after 12 weeks of treatment. The study will evaluate 5 different doses of omarigliptin to identify which dose is the most effective in the treatment of type 2 diabetes.

Detailed Description

MK-3102-006-Ext 1 added a 66-week extension to the base study (MK-3102 P006) to assess the long-term safety and tolerability of omarigliptin. To be eligible for the extension, participants must complete the double-blind base study, must have had at least a 75% compliance with study drug during the base study and can not meet any of the criteria for discontinuation. Participants randomized to placebo in the base study will be switched in a blinded manner to pioglitazone 30 mg once daily, in the extension study prior to implementation of amendment P006-13. Once amendment P006-13 has been IRB/IEC approved and blinded metformin drug supply is available at the site, participants will be switched from pioglitazone to metformin, starting at 500 mg once daily and titrated up to 1000 mg twice daily. Participants with a contraindication to metformin will be discontinued from the study. Participants randomized to 0.25 mg, 1 mg, 3 mg, and 10 mg of omarigliptin in the base study will be switched to omarigliptin 25 mg; those randomized to 25 mg of omarigliptin in the base study will continue on the same dose in the extension study. After the clinical dose of omarigliptin selected for further development has been identified based upon the results of the base study, all participants randomized to omarigliptin will be switched to the identified clinical dose.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Omarigliptin 0.25 mg (Base)

Omarigliptin 0.25 mg administered once weekly for 12 weeks (Base)

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.

Omarigliptin 1 mg (Base)

Omarigliptin 1 mg administered once weekly for 12 weeks (Base)

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.

Omarigliptin 3 mg (Base)

Omarigliptin 3 mg administered once weekly for 12 weeks (Base)

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.

Omarigliptin 10 mg (Base)

Omarigliptin 10 mg administered once weekly for 12 weeks (Base)

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.

Omarigliptin 25 mg (Base)

Omarigliptin 25 mg administered once weekly for 12 weeks (Base)

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.

Placebo (Base)

Matching placebo to omarigliptin administered once weekly for 12 weeks (Base)

Group Type: PLACEBO_COMPARATOR

Placebo to omarigliptin

Intervention Type: DRUG

Matching placebo to omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For matching placebo to omarigliptin 3 mg, participants received two matching placebo to omarigliptin 1.5 mg capsules.

Pooled omarigliptin (Extension)

Participants who received omarigliptin during the base study, received omarigliptin 25 mg once weekly and placebo to metformin once daily for 66 weeks (Extension).

Group Type: EXPERIMENTAL

Omarigliptin

Intervention Type: DRUG

Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.

Placebo to metformin

Intervention Type: DRUG

Matching placebo to metformin oral tablet administered once daily

Placebo/Metformin

Participants who received matching placebo to omarigliptin during the base period, received pioglitazone administered once daily and matching placebo to omarigliptin once weekly for 66 weeks (extension period). Note: A protocol amendment removed pioglitazone during the extension period. Participants discontinued pioglitazone and switched to blinded metformin. Participants who were previously rescued with open-label metformin during the base period continued in the extension period on open-label metformin.

Group Type: ACTIVE_COMPARATOR

Placebo to omarigliptin

Intervention Type: DRUG

Matching placebo to omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For matching placebo to omarigliptin 3 mg, participants received two matching placebo to omarigliptin 1.5 mg capsules.

Pioglitazone

Intervention Type: DRUG

Pioglitazone 15 mg oral tablet or capsule administered once daily

Metformin

Intervention Type: DRUG

Metformin 500 mg oral tablet administered once or twice daily

Interventions

Omarigliptin

Omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For omarigliptin 3 mg, participants received two omarigliptin 1.5 mg capsules.

Intervention Type: DRUG

Placebo to omarigliptin

Matching placebo to omarigliptin 0.25, 1, 1.5, 10 or 25 mg oral capsule administered once weekly. For matching placebo to omarigliptin 3 mg, participants received two matching placebo to omarigliptin 1.5 mg capsules.

Intervention Type: DRUG

Pioglitazone

Pioglitazone 15 mg oral tablet or capsule administered once daily

Intervention Type: DRUG

Metformin

Metformin 500 mg oral tablet administered once or twice daily

Intervention Type: DRUG

Placebo to metformin

Matching placebo to metformin oral tablet administered once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

The prospective participant must meet, at least, all of the criteria below (among others determined by the study staff) to be eligible for study participation.

The participant:

• Has type 2 diabetes mellitus and is between 18 and 70 years of age; for Japan, 20 to 70 years of age;
• Has a body mass index (BMI) > 20 kg/m^2 and < 43 kg/m^2; for Japan: BMI >18 kg/m^2 and <43 kg/m^2;
• Is currently not on an antihyperglycemic agent (AHA) medication (off for ≥ 14 weeks) or is on oral AHA therapy but has inadequate glycemic control;
• Is a male, or a female who is highly unlikely to conceive.

Exclusion Criteria

If the prospective participant meets any of the criteria below (among others determined by the study staff) they will NOT be eligible for study participation.

The participant:

• Has a history of type 1 diabetes mellitus or a history of ketoacidosis;
• Is on a weight loss program or has started a weight loss medication within the prior 8 weeks;
• Has required insulin therapy within 14 weeks prior to signing informed consent;
• Has a medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic active hepatitis B or C, cirrhosis, or symptomatic gallbladder disease;
• Has congestive heart failure or has new or worsening signs or symptoms of coronary heart disease;
• Had any of the following disorders within the past 3 months: acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder;
• Has a history of malignancy or clinically important hematological disorder

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Sheu WH, Gantz I, Chen M, Suryawanshi S, Mirza A, Goldstein BJ, Kaufman KD, Engel SS. Safety and Efficacy of Omarigliptin (MK-3102), a Novel Once-Weekly DPP-4 Inhibitor for the Treatment of Patients With Type 2 Diabetes. Diabetes Care. 2015 Nov;38(11):2106-14. doi: 10.2337/dc15-0109. Epub 2015 Aug 26.

Reference Type: RESULT

PMID: 26310692 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

2010-022193-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2011-000656-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

3102-006

Identifier Type: -

Identifier Source: org_study_id