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

NCT01217073 | Completed Phase 2 Results

• 3 other identifiers: 3102-0062010-022193-132011-000656-42
• Study Type: interventional
• Target: 685
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (5)

• 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

• 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)

• 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

• 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)

• 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 Outcomes (8)

• Change From Baseline in 2 Hour-post-meal Glucose (2h-PMG) Levels at Week 12

  Baseline (Week 0) and Week 12

• Change From Baseline in Fasting Plasma Glucose (FPG) Levels at Week 12

  Baseline (Week 0) and Week 12

• Mean Plasma A1C Level at Baseline of the Extension Period

  Baseline (Week 0)

• Change From Baseline in Plasma A1C Levels at Week 78

  Baseline (Week 0) and Week 78

• Mean 2h-PMG Level at Baseline of the Extension Period

  Baseline (Week 0)

Study Arms (8)

Omarigliptin 0.25 mg (Base)

EXPERIMENTAL

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

Drug: Omarigliptin

Omarigliptin 1 mg (Base)

EXPERIMENTAL

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

Drug: Omarigliptin

Omarigliptin 3 mg (Base)

EXPERIMENTAL

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

Drug: Omarigliptin

Omarigliptin 10 mg (Base)

EXPERIMENTAL

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

Drug: Omarigliptin

Omarigliptin 25 mg (Base)

EXPERIMENTAL

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

Drug: Omarigliptin

Placebo (Base)

PLACEBO COMPARATOR

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

Drug: Placebo to omarigliptin

Pooled omarigliptin (Extension)

EXPERIMENTAL

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; Drug: Placebo to metformin

Placebo/Metformin

ACTIVE COMPARATOR

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; Drug: Pioglitazone; Drug: Metformin

Interventions

Omarigliptin 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 0.25 mg (Base); Omarigliptin 1 mg (Base); Omarigliptin 10 mg (Base); Omarigliptin 25 mg (Base); Omarigliptin 3 mg (Base); Pooled omarigliptin (Extension)

Placebo to omarigliptin 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.

Placebo (Base); Placebo/Metformin

Pioglitazone DRUG

Pioglitazone 15 mg oral tablet or capsule administered once daily

Placebo/Metformin

Metformin DRUG

Metformin 500 mg oral tablet administered once or twice daily

Placebo/Metformin

Placebo to metformin DRUG

Matching placebo to metformin oral tablet administered once daily

Pooled omarigliptin (Extension)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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):2106-14. doi: 10.2337/dc15-0109. Epub 2015 Aug 26.

  PMID: 26310692 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl)-2,6-dihydropyrrolo(3,4-c)pyrazol-5(4H)-yl)tetrahydro-2H-pyran-3-amine; Pioglitazone; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2010
• First Posted: October 8, 2010
• Study Start: October 8, 2010
• Primary Completion: January 3, 2012
• Study Completion: April 1, 2013
• Last Updated: September 10, 2018
• Results First Posted: October 29, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share