A Study of the Safety and Efficacy of Omarigliptin (MK-3102) in ≥18 and <45 Year-Old Participants With Type 2 Diabetes Mellitus and Inadequate Glycemic Control (MK-3102-028)

NCT01814748 | Completed Phase 3 Results DMC

• 2 other identifiers: 3102-0282012-004303-12
• Study Type: interventional
• Target: 203
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will examine the safety and efficacy of once-weekly omarigliptin in participants 18 to \<45 years of age with Type 2 diabetes mellitus and inadequate glycemic control. The study hypothesis is that treatment with omarigliptin compared with placebo provides greater reduction in hemoglobin A1c (A1C) in participants after 24 weeks.

Conditions

Diabetes Mellitus

Keywords

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Metformin; Hypoglycemic Agents; Pharmacologic Actions; Therapeutic Uses

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in A1C at Week 24

  A1C (%) is used to report average blood glucose levels over prolonged periods of time. The unexpected absence of a treatment effect in this study led to investigations that included measurement of metformin levels in available samples collected for future research during the study. Of the 92 participants with samples who had not been rescued with metformin, 57% (25/44) in the placebo group and 29% (14/48) in the omarigliptin group had detectable metformin, indicating the use of metformin that was prohibited by the protocol. The use of metformin prohibited by the protocol was without investigator knowledge and is a confounding factor impacting the ability to draw any conclusions regarding the efficacy results from this study.

  Baseline and Week 24

• Percentage of Participants Who Experienced at Least One Adverse Event (AE)

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Data presented exclude data following the initiation of glycemic rescue. The safety database was analyzed in a standard fashion in the all participants as treated (APaT) population for all participants who took at least one dose of study medication. This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).

  Up to Week 27

• Percentage of Participants Who Discontinued Study Drug Due to an AE

  An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Data presented exclude data following the initiation of glycemic rescue. The safety database was analyzed in a standard fashion in the APaT population for all participants who took at least one dose of study medication. This analysis may have been confounded by the use of metformin prohibited by the protocol (see efficacy results description above).

  Up to Week 24

Secondary Outcomes (5)

• Change From Baseline in 2-hr PMG at Week 24

  Baseline and Week 24

• Change in Baseline in FPG at Week 24

  Baseline and Week 24

• Percentage of Participants Attaining A1C Glycemic Goals of <7.0% at Week 24

  Week 24

• Percentage of Participants Attaining A1C Glycemic Goals of <6.5% (48 mmol/Mol) at Week 24

  Week 24

• Percentage of Participants Who Required Glycemic Rescue by Week 24

  Up to Week 24

Study Arms (2)

Omarigliptin 25 mg

EXPERIMENTAL

Omarigliptin 25 mg, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.

Drug: Omarigliptin; Drug: Metformin

Placebo

PLACEBO COMPARATOR

Placebo to omarigliptin, once weekly, for 24 weeks. Open-label metformin daily was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.

Drug: Placebo to omarigliptin; Drug: Metformin

Interventions

Omarigliptin DRUG

Omarigliptin 25 mg capsule administered orally once weekly

Also known as: MK-3102

Omarigliptin 25 mg

Placebo to omarigliptin DRUG

Matching placebo to omarigliptin 25 mg capsule administered orally once weekly

Placebo

Metformin DRUG

Open-label metformin (dosed daily according to the country-specific product label) was to be initiated for participants meeting protocol-specified glycemic criteria, but was otherwise prohibited.

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

Omarigliptin 25 mg; Placebo

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Has type 2 diabetes mellitus
• Currently not on an antihyperglycemic agent (AHA) for at least the past 12 weeks and has not been treated with omarigliptin at any time prior to study participation
• 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 her partner use) 2 acceptable methods of 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
• History of hypersensitivity to dipeptidyl-peptidase-4 (DPP-4) inhibitor
• Currently participating in or has participated in a clinical trial in the past 12 weeks
• Is on a weight loss program and not in the maintenance phase; has been on 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 pharmacologic doses of corticosteroids
• Is currently being treated for hyperthyroidism or is on thyroid replacement 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 hepatic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
• Has 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Gantz I, Sokolova L, Jain L, Iredale C, O'Neill EA, Wei Z, Lam R, Suryawanshi S, Kaufman KD, Engel SS, Lai E. Use of Prohibited Medication, a Potentially Overlooked Confounder in Clinical Trials: Omarigliptin (Once-weekly DPP-4 Inhibitor) Monotherapy Trial in 18- to 45-year-olds. Clin Ther. 2017 Oct;39(10):2024-2037. doi: 10.1016/j.clinthera.2017.08.009. Epub 2017 Sep 18.

  PMID: 28923291 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Interventions

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

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Investigations indicate that the presence of metformin in future biomedical research (FBR) samples from non-rescued participants was due to participant self-administration of metformin outside of the protocol and without investigator knowledge.

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2013
• First Posted: March 20, 2013
• Study Start: May 3, 2013
• Primary Completion: September 14, 2015
• Study Completion: September 14, 2015
• Last Updated: September 10, 2018
• Results First Posted: July 18, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share