A Study to Assess the Safety and Efficacy of Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus (T2DM) and Inadequate Glycemic Control (MK-3102-011)

NCT01717313 | Completed Phase 3 Results DMC

• 2 other identifiers: 3102-0112012-003626-24
• Study Type: interventional
• Target: 329
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to assess the safety and efficacy of omarigliptin (MK-3102), dosed once-weekly in participants with T2DM who have inadequate glycemic control on diet and exercise. The primary hypothesis is that after 24 weeks, treatment with omarigliptin compared with placebo provides greater reduction in hemoglobin A1c (A1C).

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (5)

• Change From Baseline in Hemoglobin A1c (A1C) at Week 24 (Phase A, FAS Population)

  A1C (%) is used to report average blood glucose levels over prolonged periods of time. Because it was discovered that in another omarigliptin study (MK-3102-028, NCT01814748) subjects had taken metformin (prohibited per protocol, and taken without investigator knowledge), after unblinding of Phase A of this study, an analysis of metformin levels was performed on stored Week 18 blood samples. Of the subjects not rescued with metformin prior to Week 18, 10% in the omarigliptin group and 20% in the placebo group had levels showing that they were taking metformin (prohibited per protocol). The use of prohibited metformin disproportionately by the placebo group may have resulted in a smaller than expected treatment effect for efficacy outcome measures (see post-hoc analysis).

  Baseline and Week 24

• Percentage of Participants Who Experienced at Least One Adverse Event in Phase A (Excluding Data After Glycemic Rescue, Safety Population)

  An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

  Up to 27 weeks

• Percentage of Participants Who Discontinued From the Study Drug Due to an Adverse Event in Phase A (Excluding Data After Glycemic Rescue, Safety Population)

  An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

  Up to 24 weeks

• Percentage of Participants Who Experienced at Least One Adverse Event (Phase A + Phase B, Excluding Data After Glycemic Rescue, Safety Population)

  An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

  Up to 57 weeks

• Percentage of Participants Who Discontinued From the Study Drug Due to an Adverse Event (Phase A + Phase B, Excluding Data After Glycemic Rescue, Safety Population)

  An adverse event is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the treatment. Adverse events may include the onset of new illness and the exacerbation of preexisting conditions. This analysis may have been confounded by use of prohibited metformin (see results above for description of the use of prohibited metformin).

  Up to 57 weeks

Secondary Outcomes (8)

• Percentage of Participants Who Achieve an A1C Goal of <7% (53 mmol/Mol) at Week 24 (Phase A, FAS Population)

  Week 24

• Percentage of Participants Who Achieve an A1C Goal of <6.5% (48 mmol/Mol) at Week 24 (Phase A, FAS Population)

  Week 24

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Phase A, FAS Population)

  Baseline and Week 24

• Change From Baseline in 2-hour Post Meal Glucose (PMG) at Week 24 (Phase A, FAS Population)

  Baseline and Week 24

• Change From Baseline in A1C at Week 54 (Phase A + Phase B, FAS Population)

  Baseline and Week 54

Study Arms (2)

Omarigliptin

EXPERIMENTAL

Omarigliptin 25 mg capsule administered orally once a week for 24 weeks (Phase A) followed by omarigliptin 25 mg administered orally once a week plus placebo to metformin daily (Phase B). Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B.

Drug: Omarigliptin; Drug: Metformin; Drug: Placebo to metformin; Drug: Glimepiride

Placebo to Omarigliptin

PLACEBO COMPARATOR

Placebo to omarigliptin administered orally once a week for 24 weeks (Phase A) followed by placebo to omarigliptin administered orally once a week plus metformin daily for an additional 30 weeks (Phase B). Open-label metformin was to be initiated for participants meeting protocol-specified glycemic criteria during Phase A, but was otherwise prohibited. Open-label glimepiride daily may be initiated as glycemic rescue therapy during Phase B.

Drug: Placebo to Omarigliptin; Drug: Metformin; Drug: Glimepiride

Interventions

Omarigliptin DRUG

Omarigliptin 25 mg capsule administered orally once a week.

Omarigliptin

Placebo to Omarigliptin DRUG

Placebo to omarigliptin capsule administered orally once a week

Placebo to Omarigliptin

Metformin DRUG

If necessary, participants may have glycemic rescue therapy initiated with open-label metformin during Phase A of the study. Participants in the placebo treatment group who were not rescued with open-label metformin during Phase A will receive blinded metformin (starting at 500 mg orally twice daily with up-titration to 1000 mg orally twice daily) in Phase B. Participants in the omarigliptin treatment group who were rescued with open-label metformin in Phase A will continue open-label metformin during Phase B of the study.

Also known as: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®

Omarigliptin; Placebo to Omarigliptin

Placebo to metformin DRUG

During Phase B of the study, participants in the omarigliptin treatment group who did not initiate glycemic rescue therapy during Phase A will receive placebo to metformin for 30 weeks (Phase B of the study).

Omarigliptin

Glimepiride DRUG

If necessary during Phase B of the study, participants will initiate open-label glimepiride as glycemic rescue therapy

Also known as: Armaryl®

Omarigliptin; Placebo to Omarigliptin

Eligibility Criteria

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

You may qualify if:

• Has type 2 diabetes mellitus
• Participants in India must be ≤65 years of age
• Meets one of the following criteria: currently not on an antihyperglycemic agent (AHA) for \>= 12 weeks and has an A1C of \>=7% and \<=10% or on stable AHA monotherapy or low-dose combination therapy for \> 12 weeks and has an A1C of \>=6.5% and \<=9%
• Participant is one of the following: male, female who is not of reproductive potential, female of reproductive potential who agrees to remain abstinent from heterosexual activity or use (or have their partner use) acceptable contraception to prevent pregnancy during the study and for 21 days after the last dose of study drug

You may not qualify if:

• History of type 1 diabetes mellitus or a history of ketoacidosis
• Has been treated with: a thiazolidinedione (TZD) within 4 months of study participation, a glucagon-like peptide-1 (GLP-1) receptor mimetic or agonist or dipeptidyl peptidase IV (DPP-4) inhibitor within 6 months of study participation, insulin or sodium-glucose cotransporter inhibitor within 12 weeks of study participation, omarigliptin at any time prior to study participation
• History of hypersensitivity to DPP-4 inhibitor
• History of intolerance, hypersensitivity or any contraindication to metformin and/or glimepiride or other sulfonylurea
• Is on a weight loss program and not in the maintenance phase or has started a weight loss medication in the past 6 months or has undergone bariatric surgery within 12 months prior to study participation
• Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study
• Is on or likely to require treatment for ≥14 consecutive days or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
• Is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
• Is expecting to undergo hormonal therapy in preparation to donate eggs during the study, including 21 days following the last dose of study drug
• History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
• Human immunodeficiency virus (HIV)
• Has had new or worsening coronary heart disease or congestive heart failure within the past 3 months, or has any of the following disorders within the past 3 months: acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder
• Has poorly controlled hypertension
• History of malignancy \<=5 years prior to study participation, except for basal cell or squamous cell skin cancer or in situ cervical cancer
• Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Home P, Shankar RR, Gantz I, Iredale C, O'Neill EA, Jain L, Pong A, Suryawanshi S, Engel SS, Kaufman KD, Lai E. A randomized, double-blind trial evaluating the efficacy and safety of monotherapy with the once-weekly dipeptidyl peptidase-4 inhibitor omarigliptin in people with type 2 diabetes. Diabetes Res Clin Pract. 2018 Apr;138:253-261. doi: 10.1016/j.diabres.2017.10.018. Epub 2017 Oct 24.

  PMID: 29079379 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; Metformin; glimepiride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Care must be taken in the interpretation of the results in this study as the non-protocol-specified prohibited use of metformin among a number of participants may have impacted the safety and efficacy results disproportionally among study arms.

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 3
• 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 26, 2012
• First Posted: October 30, 2012
• Study Start: December 5, 2012
• Primary Completion: June 19, 2015
• Study Completion: June 19, 2015
• Last Updated: September 10, 2018
• Results First Posted: July 25, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share