A Study to Evaluate the Safety, Tolerability, and Efficacy of the Addition of MK-3102 to Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy (MK-3102-024)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01755156
First received: December 18, 2012
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to assess the safety and efficacy of MK-3102 compared to placebo in participants with inadequate glycemic control on metformin monotherapy. The primary hypothesis is that after 24 weeks, the addition of treatment with MK-3102 provides greater reduction in hemoglobin A1c (A1C) than placebo.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: MK-3102
Drug: Matching placebo to MK-3102
Drug: Glimepiride
Drug: Matching placebo to glimepiride
Drug: Insulin glargine
Drug: Metformin
Phase 3

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 Multicenter, Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Efficacy of the Addition of MK-3102 to Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin Therapy

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change from baseline in A1C at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Percentage of participants who experienced at least one adverse event [ Time Frame: Up to 107 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of participants who discontinued study drug due to an adverse event [ Time Frame: Up to 104 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of participants who experienced a laboratory abnormality [ Time Frame: Up to 104 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in 2-hour post-meal glucose (PMG) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose (FPG) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in A1C at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Change from baseline in FPG at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Proportion of participants attaining A1C glycemic goals of <7% and <6.5% after 24 weeks of treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Proportion of participants attaining A1C glycemic goals of <7% and <6.5% after 104 weeks of treatment [ Time Frame: 104 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in PMG total area under the curve (AUC) at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in fasting insulin at Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in fasting insulin at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: No ]
  • Time to rescue over 24 weeks [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
  • Time to rescue over 104 weeks [ Time Frame: Up to 104 weeks ] [ Designated as safety issue: No ]
  • Proportion of participants requiring rescue therapy at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Proportion of participants requiring rescue therapy at Week 104 [ Time Frame: Week 104 ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: January 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-3102
MK-3102 25 mg capsule administered orally once weekly for 104 weeks (24 weeks during Phase A, 80 weeks during Phase B) and matching placebo to glimepiride tablet administered orally once daily for 80 weeks (Phase B). Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and open-label insulin glargine during Phase B).
Drug: MK-3102
MK-3102 25 mg capsule administered orally once weekly (preferably on the same day of each week)
Drug: Matching placebo to glimepiride
Matching placebo to glimepiride tablet administered orally once daily and up-titrated to a mock maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.
Drug: Insulin glargine
During Phase B of the study, participants who received a maximum up-titration of open-label glimepiride or blinded glimepiride/matching placebo to glimepiride, may be rescued with open-label insulin glargine.
Other Name: Lantus
Drug: Metformin
Participants continue stable pre-study dose of metformin tablet(s) administered orally (>= 1500 mg daily) throughout the study.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Placebo Comparator: Matching placebo to MK-3102
Matching placebo to MK-3102 capsule administered orally once weekly for 104 weeks (24 weeks during Phase A, 80 weeks during Phase B) and glimepiride 1 or 2 mg tablet administered orally once daily (titrated up to 6 mg daily) for 80 weeks (Phase B). Participants will continue pre-study metformin throughout the duration of the study. If necessary, rescue therapy may be initiated (open-label glimepiride during Phase A and insulin glargine during Phase B).
Drug: Matching placebo to MK-3102
Matching placebo to MK-3102 capsule administered orally once weekly (preferably on the same day of each week)
Drug: Glimepiride
Glimepiride 1 or 2 mg tablet administered orally once daily and up-titrated to a maximum dose of 6 mg daily. Participants rescued with open-label glimepiride during Phase A will not receive glimepiride or matching placebo to glimepiride during Phase B.
Other Name: Amaryl®
Drug: Insulin glargine
During Phase B of the study, participants who received a maximum up-titration of open-label glimepiride or blinded glimepiride/matching placebo to glimepiride, may be rescued with open-label insulin glargine.
Other Name: Lantus
Drug: Metformin
Participants continue stable pre-study dose of metformin tablet(s) administered orally (>= 1500 mg daily) throughout the study.
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has type 2 diabetes mellitus
  • Currently on a stable dose of metformin monotherapy (>=1500 mg per day) for at least 12 weeks prior to study participation
  • Male, or female who is not of reproductive potential or if of reproductive potential agrees to abstain 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

Exclusion Criteria:

  • History of type 1 diabetes mellitus or a history of ketoacidosis
  • Has been treated with any antihyperglycemic agent (AHA) other than the protocol-required metformin within 12 weeks prior to study participation or with MK-3102 at any time prior to signing informed consent
  • History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor
  • History of intolerance, hypersensitivity, or any other contraindication to metformin, glimepiride, or insulin glargine
  • Is 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
  • 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 >=2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
  • Currently being treated for hyperthyroidism or is on thyroid hormone 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 period of the trial, including 21 days after the last dose of blinded study medication
  • 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)
  • New or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, stroke, or transient ischemic attacks in the past 3 months
  • Poorly controlled hypertension
  • History of malignancy <=5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
  • Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
  • Positive urine pregnancy test
  • Pregnant or breastfeeding, or is expecting to conceive during the study including 21 days following the last dose of blinded study drug
  • User of recreational or illicit drugs or has had a recent history of drug abuse
  • Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking
  • Has donated blood products or has had phlebotomy of >300 mL within 8 weeks of study participation, or intends to donate blood products within the projected duration of the trial or has received, or is anticipated to receive, blood products within 12 weeks of study participation or within the projected duration of the trial
  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: NCT01755156

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

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01755156     History of Changes
Other Study ID Numbers: 3102-024
Study First Received: December 18, 2012
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Glargine
Insulin
Metformin
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 20, 2014