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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Omarigliptin; Drug: Placebo to metformin; Drug: Metformin; Drug: Pioglitazone; Drug: Placebo to omarigliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01217073

2011-000656-42 (EudraCT Number)

2010-022193-13 (EudraCT Number)

3102-006

Details and patient eligibility

About

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.

Full 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.

Enrollment: 685 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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685 participants in 8 patient groups, including a placebo group

Omarigliptin 0.25 mg (Base)

Experimental group

Description:

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

Treatment:

Drug: Omarigliptin

Omarigliptin 1 mg (Base)

Experimental group

Description:

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

Treatment:

Drug: Omarigliptin

Omarigliptin 3 mg (Base)

Experimental group

Description:

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

Treatment:

Drug: Omarigliptin

Omarigliptin 10 mg (Base)

Experimental group

Description:

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

Treatment:

Drug: Omarigliptin

Omarigliptin 25 mg (Base)

Experimental group

Description:

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

Treatment:

Drug: Omarigliptin

Placebo (Base)

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo to omarigliptin

Pooled omarigliptin (Extension)

Experimental group

Description:

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

Treatment:

Drug: Placebo to metformin

Drug: Omarigliptin

Placebo/Metformin

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to omarigliptin

Drug: Metformin

Drug: Pioglitazone