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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01217073
First received: October 6, 2010
Last updated: November 25, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Omarigliptin
Drug: Placebo to omarigliptin
Drug: Pioglitazone
Drug: Metformin
Drug: Placebo to metformin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change From Baseline in Plasma A1C Levels at Week 12 [ Time Frame: Baseline (Week 0) and Week 12 ] [ Designated as safety issue: No ]
    A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 12 level.

  • Percentage of Participants Who Experienced at Least One Adverse Event During the Base Period [ Time Frame: Up to 16 weeks (including 28 days following the last dose of study drug) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event During the 12-week Base Period [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Experienced at Least One Adverse Event During the 66-week Extension Period [ Time Frame: Up to 70 Weeks (Weeks 12 to 78 plus 4-week follow-up period) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Who Discontinued From Study Drug Due to an Adverse Event During the 66-week Extension Period [ Time Frame: Up to 66 weeks (Weeks 12 to 78) ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12 [ Time Frame: Baseline (Week 0) and Week 12 ] [ Designated as safety issue: No ]
    Change from baseline was calculated by subtracting the baseline level from the Week 12 level.

  • Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12 [ Time Frame: Baseline (Week 0) and Week 12 ] [ Designated as safety issue: No ]
    Change from baseline was calculated by subtracting the baseline level from the Week 12 level.

  • Mean Plasma A1C Level at Baseline of the Extension Period [ Time Frame: Baseline (Week 0) ] [ Designated as safety issue: No ]
    A1C levels were measured as a percent at baseline (Week 0) for participants who entered the extension period.

  • Change From Baseline in Plasma A1C Levels at Week 78 [ Time Frame: Baseline (Week 0) and Week 78 ] [ Designated as safety issue: No ]
    A1C levels were measured as a percent. Change from baseline was calculated by subtracting the baseline level from the Week 78 level.

  • Mean 2h-PMG Level at Baseline of the Extension Period [ Time Frame: Baseline (Week 0) ] [ Designated as safety issue: No ]
    Plasma 2h-PMG levels were measured at baseline (Week 0) for participants who entered the extension period.

  • Change From Baseline in 2h-PMG at Week 78 [ Time Frame: Baseline (Week 0) and Week 78 ] [ Designated as safety issue: No ]
    Change from baseline was calculated by subtracting the baseline level from the Week 78 level.

  • Mean FPG Level at Baseline of the Extension Period [ Time Frame: Baseline (Week 0) ] [ Designated as safety issue: No ]
    Plasma FPG levels were measured at baseline (Week 0) for particiapnts who entered the extension period.

  • Change From Baseline in FPG Levels at Week 78 [ Time Frame: Baseline (Week 0) and Week 78 ] [ Designated as safety issue: No ]
    Change from baseline was calculated by subtracting the baseline level from the Week 78 level.


Enrollment: 685
Study Start Date: October 2010
Study Completion Date: April 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Omarigliptin 0.25 mg (Base)
Omarigliptin 0.25 mg administered once weekly for 12 weeks (Base)
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.
Experimental: Omarigliptin 1 mg (Base)
Omarigliptin 1 mg administered once weekly for 12 weeks (Base)
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.
Experimental: Omarigliptin 3 mg (Base)
Omarigliptin 3 mg administered once weekly for 12 weeks (Base)
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.
Experimental: Omarigliptin 10 mg (Base)
Omarigliptin 10 mg administered once weekly for 12 weeks (Base)
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.
Experimental: Omarigliptin 25 mg (Base)
Omarigliptin 25 mg administered once weekly for 12 weeks (Base)
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 Comparator: Placebo (Base)
Matching placebo to omarigliptin administered once weekly for 12 weeks (Base)
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.
Experimental: 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).
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.
Drug: Placebo to metformin
Matching placebo to metformin oral tablet administered once daily
Active Comparator: 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.
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.
Drug: Pioglitazone
Pioglitazone 15 mg oral tablet or capsule administered once daily
Drug: Metformin
Metformin 500 mg oral tablet administered once or twice daily

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01217073

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01217073     History of Changes
Other Study ID Numbers: 3102-006  2010-022193-13  2011-000656-42 
Study First Received: October 6, 2010
Results First Received: September 29, 2015
Last Updated: November 25, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Metformin
Pioglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 04, 2016