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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)

Primary Purpose

Type 2 Diabetes Mellitus

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Omarigliptin
Placebo to omarigliptin
Glipizide
Placebo to glipizide
Insulin
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes Mellitus

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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:

    1. is currently not on an antihyperglycemic agent (AHA) and has A1C >=7% and <=10% at screening
    2. is currently on a single oral AHA or low-dose dual oral combination AHA and has A1C >=6.5% and <=9% at screening
    3. 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

Exclusion Criteria:

  • 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
  • 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
  • Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
  • Positive pregnancy test
  • Pregnant or breast-feeding, or is expecting to conceive or donate eggs during the trial, including 28 days following the last dose of study drug
  • User of recreational or illicit drugs or has had a recent history of drug abuse or routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Omarigliptin (Phase A) → Omarigliptin (Phase B)

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

    Arm Description

    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).

    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).

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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.
    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.
    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.

    Secondary Outcome Measures

    Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
    Change from baseline in FPG at Week 24 was analyzed using 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.
    Change From Baseline in A1C at Week 54
    A1C is measured as a percent. Change from baseline in A1C at Week 54 was analyzed using 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.
    Change From Baseline in FPG at Week 54
    Change from baseline in FPG at Week 54 was analyzed using 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.
    Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24
    Based on an cLDA model including terms for treatment, renal status stratum, treatment on insulin at screening stratum, time, the interaction of time by treatment, the interaction of time by renal status stratum, and the interaction of time by treatment on insulin at screening stratum, with the constraint that the mean baseline is the same for all treatment groups. Excluding data after glycemic rescue or initiation of dialysis as well as participants classified with end stage renal disease (ESRD) on dialysis.
    Change From Baseline in eGFR at Week 54
    Based on an cLDA model including terms for treatment, renal status stratum, treatment on insulin at screening stratum, time, the interaction of time by treatment, the interaction of time by renal status stratum, and the interaction of time by treatment on insulin at screening stratum, with the constraint that the mean baseline is the same for all treatment groups. Excluding data after glycemic rescue or initiation of dialysis as well as participants classified with ESRD on dialysis.

    Full Information

    First Posted
    October 1, 2012
    Last Updated
    August 8, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01698775
    Brief Title
    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)
    Official Title
    A Phase III, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of MK-3102 Versus Placebo in Subjects With Type 2 Diabetes Mellitus With Moderate or Severe Chronic Kidney Disease or Kidney Failure on Dialysis Who Have Inadequate Glycemic Control.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    October 2, 2012 (Actual)
    Primary Completion Date
    January 19, 2016 (Actual)
    Study Completion Date
    January 19, 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 2 Diabetes Mellitus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    213 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Omarigliptin (Phase A) → Omarigliptin (Phase B)
    Arm Type
    Experimental
    Arm Description
    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).
    Arm Title
    Placebo to omarigliptin (Phase A) → Glipizide (Phase B)
    Arm Type
    Active Comparator
    Arm Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Omarigliptin
    Other Intervention Name(s)
    MK-3102
    Intervention Description
    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
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to omarigliptin
    Intervention Description
    Matching placebo to omarigliptin capsule administered orally once a week
    Intervention Type
    Drug
    Intervention Name(s)
    Glipizide
    Other Intervention Name(s)
    Glucotrol, Glucotrol XL
    Intervention Description
    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).
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to glipizide
    Intervention Description
    Matching placebo to glipizide daily
    Intervention Type
    Biological
    Intervention Name(s)
    Insulin
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24
    Description
    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.
    Time Frame
    Baseline and Week 24
    Title
    Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period)
    Description
    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.
    Time Frame
    Up to 28 weeks (including 28 days following the last dose of study therapy for participants who discontinued study drug)
    Title
    Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period)
    Description
    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.
    Time Frame
    Up to 24 weeks
    Title
    Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)
    Description
    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.
    Time Frame
    Up to 58 weeks (including 28 days following the last dose of study therapy)
    Title
    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)
    Description
    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.
    Time Frame
    Up to 54 weeks
    Secondary Outcome Measure Information:
    Title
    Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
    Description
    Change from baseline in FPG at Week 24 was analyzed using 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.
    Time Frame
    Baseline and Week 24
    Title
    Change From Baseline in A1C at Week 54
    Description
    A1C is measured as a percent. Change from baseline in A1C at Week 54 was analyzed using 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.
    Time Frame
    Baseline and Week 54
    Title
    Change From Baseline in FPG at Week 54
    Description
    Change from baseline in FPG at Week 54 was analyzed using 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.
    Time Frame
    Baseline and Week 54
    Title
    Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24
    Description
    Based on an cLDA model including terms for treatment, renal status stratum, treatment on insulin at screening stratum, time, the interaction of time by treatment, the interaction of time by renal status stratum, and the interaction of time by treatment on insulin at screening stratum, with the constraint that the mean baseline is the same for all treatment groups. Excluding data after glycemic rescue or initiation of dialysis as well as participants classified with end stage renal disease (ESRD) on dialysis.
    Time Frame
    Baseline and Week 24
    Title
    Change From Baseline in eGFR at Week 54
    Description
    Based on an cLDA model including terms for treatment, renal status stratum, treatment on insulin at screening stratum, time, the interaction of time by treatment, the interaction of time by renal status stratum, and the interaction of time by treatment on insulin at screening stratum, with the constraint that the mean baseline is the same for all treatment groups. Excluding data after glycemic rescue or initiation of dialysis as well as participants classified with ESRD on dialysis.
    Time Frame
    Baseline and Week 54

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    30 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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 Exclusion Criteria: 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 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 Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) Positive pregnancy test Pregnant or breast-feeding, or is expecting to conceive or donate eggs during the trial, including 28 days following the last dose of study drug User of recreational or illicit drugs or has had a recent history of drug abuse or routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    28449320
    Citation
    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.
    Results Reference
    result

    Learn more about this trial

    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)

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