A Study of Omarigliptin (MK-3102) in Participants With Type 2 Diabetes Mellitus With Chronic Kidney Disease or Kidney Failure on Dialysis (MK-3102-019)

NCT01698775 | Completed Phase 3 Results DMC

• 2 other identifiers: 3102-0192012-002332-85
• Study Type: interventional
• Target: 213
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of omarigliptin in participants with type 2 diabetes mellitus and moderate or severe chronic renal insufficiency or end stage renal disease on dialysis with inadequate glycemic control. The primary hypothesis of the study is that omarigliptin compared to placebo produces greater reduction in glycosylated hemoglobin (A1C) after 24 weeks.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (5)

• Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24

  A1C is measured as a percent. Change from baseline in A1C at Week 24 was analyzed using constrained longitudinal data analysis (cLDA) method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, renal insufficiency stratum, baseline treatment with insulin stratum, time, the interaction of time by treatment, the interaction of time by renal insufficiency stratum, and the interaction of time by baseline treatment with insulin stratum.

  Baseline and Week 24

• Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period)

  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.

  Up to 28 weeks (including 28 days following the last dose of study therapy for participants who discontinued study drug)

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period)

  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.

  Up to 24 weeks

• Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)

  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.

  Up to 58 weeks (including 28 days following the last dose of study therapy)

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)

  An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.

  Up to 54 weeks

Secondary Outcomes (5)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

  Baseline and Week 24

• Change From Baseline in A1C at Week 54

  Baseline and Week 54

• Change From Baseline in FPG at Week 54

  Baseline and Week 54

• Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24

  Baseline and Week 24

• Change From Baseline in eGFR at Week 54

  Baseline and Week 54

Study Arms (2)

Omarigliptin (Phase A) → Omarigliptin (Phase B)

EXPERIMENTAL

Phase A: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 24 weeks. Phase B: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive matching placebo to glipizide daily in a blinded manner during Phase B of the study (Week 24 through Week 54).

Drug: Omarigliptin; Drug: Glipizide; Drug: Placebo to glipizide; Biological: Insulin

Placebo to omarigliptin (Phase A) → Glipizide (Phase B)

ACTIVE COMPARATOR

Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: matching placebo to omarigliptin orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive glipizide 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).

Drug: Placebo to omarigliptin; Drug: Glipizide; Drug: Placebo to glipizide; Biological: Insulin

Interventions

Omarigliptin DRUG

Participants with moderate renal insufficiency will receive one omarigliptin 25 mg capsule orally once a week; participants with severe renal insufficiency or end stage renal disease will receive one omarigliptin 12.5 mg capsule orally once a week

Also known as: MK-3102

Omarigliptin (Phase A) → Omarigliptin (Phase B)

Placebo to omarigliptin DRUG

Matching placebo to omarigliptin capsule administered orally once a week

Placebo to omarigliptin (Phase A) → Glipizide (Phase B)

Glipizide DRUG

Phase A: Participants may receive open-label glipizide as rescue therapy up to Week 24 of the study. Phase B: Participants who received placebo to omarigliptin during Phase A and are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study Week 1 through Week 24) will receive glipizide capsule(s) 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).

Also known as: Glucotrol, Glucotrol XL

Omarigliptin (Phase A) → Omarigliptin (Phase B); Placebo to omarigliptin (Phase A) → Glipizide (Phase B)

Placebo to glipizide DRUG

Matching placebo to glipizide daily

Omarigliptin (Phase A) → Omarigliptin (Phase B); Placebo to omarigliptin (Phase A) → Glipizide (Phase B)

Insulin BIOLOGICAL

Participants on insulin therapy at screening will continue insulin therapy during the study. Insulin glargine therapy may be administered as rescue therapy as determined by the investigator.

Omarigliptin (Phase A) → Omarigliptin (Phase B); Placebo to omarigliptin (Phase A) → Glipizide (Phase B)

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes mellitus and be at least 30 years of age
• Moderate or severe chronic renal insufficiency or end stage renal disease on dialysis
• Meet one of the following criteria:
• is currently not on an antihyperglycemic agent (AHA) and has A1C \>=7% and \<=10% at screening
• is currently on a single oral AHA or low-dose dual oral combination AHA and has A1C \>=6.5% and \<=9% at screening
• is currently on a stable insulin regimen (\>= 15 U/day) for \>= 10 weeks, with no oral AHA, and has A1C \>=7.5% and \<=10% and FPG \>130 mg/dL at screening
• (1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of contraception to prevent pregnancy during the study and for 28 days after the last dose of study drug

You may not qualify if:

• History of type 1 diabetes mellitus or a history of ketoacidosis
• Treated with any incretin mimetic or thiazolidinedione (TZD) within 12 weeks prior to screening or with omarigliptin at any time prior to study participation
• History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor
• History of intolerance or hypersensitivity to glipizide or insulin glargine or any contraindication to glipizide or insulin glargine
• On a weight loss program and is not in the maintenance phase, or has been on a weight loss medication in the past 6 months, or has undergone bariatric surgery within 12 months prior to study participation
• Undergone a surgical procedure within 4 weeks prior to screening or has planned major surgery during the trial
• On or likely to require treatment for \>=2 consecutive weeks or repeated courses of corticosteroids (note: inhaled, nasal or topical corticosteroids are permitted)
• Currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks
• If on dialysis, does not regularly adhere to dialysis schedule
• Diagnosis of congestive heart failure with New York Heart Association (NYHA) Class IV
• Medical 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
• Human immunodeficiency virus (HIV)
• New or worsening coronary heart disease, congestive heart failure, myocardial infarction, unstable angina, coronary artery intervention, stroke, or transient ischemic neurological disorder within the past 3 months
• Poorly controlled hypertension
• Severe active peripheral vascular disease

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Chacra A, Gantz I, Mendizabal G, Durlach L, O'Neill EA, Zimmer Z, Suryawanshi S, Engel SS, Lai E. A randomised, double-blind, trial of the safety and efficacy of omarigliptin (a once-weekly DPP-4 inhibitor) in subjects with type 2 diabetes and renal impairment. Int J Clin Pract. 2017 Jun;71(6):e12955. doi: 10.1111/ijcp.12955. Epub 2017 Apr 27.

  PMID: 28449320 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; Glipizide; Insulin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Sulfones; Sulfur Compounds; Organic Chemicals; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

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 1, 2012
• First Posted: October 3, 2012
• Study Start: October 2, 2012
• Primary Completion: January 19, 2016
• Study Completion: January 19, 2016
• Last Updated: August 9, 2018
• Results First Posted: February 23, 2017

Record last verified: 2017-09