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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01217073
• Other study ID #: 3102-006
• Secondary ID: 2010-022193-1320
• Status: Completed
• Phase: Phase 2
• Start date: October 8, 2010
• Est. completion date: April 1, 2013

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 685
• Est. completion date: April 1, 2013
• Est. primary completion date: January 3, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• 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.
• 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.
• Pioglitazone
Pioglitazone 15 mg oral tablet or capsule administered once daily
• Metformin
Metformin 500 mg oral tablet administered once or twice daily
• Placebo to metformin
Matching placebo to metformin oral tablet administered once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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):210 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Plasma A1C Levels at Week 12	A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 12 level.	Baseline (Week 0) and Week 12
Primary	Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period	An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.	Up to 16 weeks (including 28 days following the last dose of study drug)
Primary	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period	An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.	Up to 12 weeks
Primary	Percentage of Participants Who Experienced at Least One Adverse Event During the 66-week Extension Period	An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.	Up to 70 Weeks (Weeks 12 to 78 plus 4-week follow-up period)
Primary	Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event During the 66-week Extension Period	An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an adverse event. Data presented below excludes data after the initiation of glycemic rescue.	Up to 66 weeks (Weeks 12 to 78)
Secondary	Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12	Change from baseline was calculated by subtracting the baseline level from the Week 12 level.	Baseline (Week 0) and Week 12
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12	Change from baseline was calculated by subtracting the baseline level from the Week 12 level.	Baseline (Week 0) and Week 12
Secondary	Mean Plasma A1C Level at Baseline of the Extension Period	A1C levels were measured as a percent at baseline (Week 0) for participants who entered the extension period.	Baseline (Week 0)
Secondary	Change From Baseline in Plasma A1C Levels at Week 78	A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 78 level.	Baseline (Week 0) and Week 78
Secondary	Mean 2h-PMG Level at Baseline of the Extension Period	Plasma 2h-PMG levels were measured at baseline (Week 0) for participants who entered the extension period.	Baseline (Week 0)
Secondary	Change From Baseline in 2h-PMG at Week 78	Change from baseline was calculated by subtracting the baseline level from the Week 78 level.	Baseline (Week 0) and Week 78
Secondary	Mean FPG Level at Baseline of the Extension Period	Plasma FPG levels were measured at baseline (Week 0) for particiapnts who entered the extension period.	Baseline (Week 0)
Secondary	Change From Baseline in FPG Levels at Week 78	Change from baseline was calculated by subtracting the baseline level from the Week 78 level.	Baseline (Week 0) and Week 78