Clinical trial NCT01217073: A Dose-Range Finding Study in Participants With Type 2 Diabetes (MK-3102-006)
Official title: A Phase IIb, Randomized, Placebo-Controlled, Dose-Range Finding Clinical Trial to Study the Safety and Efficacy of MK-3102 in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-10-08
Enrollment: 685
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline in Plasma A1C Levels at Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period
timeFrame: Up to 16 weeks (including 28 days following the last dose of study drug)
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period
timeFrame: Up to 12 weeks
measure: Percentage of Participants Who Experienced at Least One Adverse Event During the 66-week Extension Period
timeFrame: Up to 70 Weeks (Weeks 12 to 78 plus 4-week follow-up period)
measure: Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event During the 66-week Extension Period
timeFrame: Up to 66 weeks (Weeks 12 to 78)
Secondary outcomes:
measure: Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Mean Plasma A1C Level at Baseline of the Extension Period
timeFrame: Baseline (Week 0)
measure: Change From Baseline in Plasma A1C Levels at Week 78
timeFrame: Baseline (Week 0) and Week 78
measure: Mean 2h-PMG Level at Baseline of the Extension Period
timeFrame: Baseline (Week 0)
measure: Change From Baseline in 2h-PMG at Week 78
timeFrame: Baseline (Week 0) and Week 78
measure: Mean FPG Level at Baseline of the Extension Period
timeFrame: Baseline (Week 0)
measure: Change From Baseline in FPG Levels at Week 78
timeFrame: Baseline (Week 0) and Week 78
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.