search
Back to results

A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)

Primary Purpose

Type 2 Diabetes Mellitus

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sitagliptin/Simvastatin FDC
Sitagliptin
Simvastatin
Placebo to sitagliptin
Placebo to simvastatin
Placebo to Sitagliptin/Simvastatin FDC
Metformin
Glimepiride
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

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • has T2DM
  • (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 14 days after the last dose of study drug
  • is currently on metformin monotherapy at a daily dose of at least 1500 mg for at least 10 weeks
  • is not on a lipid-lowering agent for at least 6 weeks prior to entering the study

Exclusion Criteria:

  • has history of type 1 diabetes mellitus (T1DM), or a history of ketoacidosis or possibly has T1DM
  • has been on a thiazolidinedione (TZD) within the previous 16 weeks
  • has been treated with a statin or other lipid-lowering agent (including over-the-counter [OTC] supplements) within the previous 6 weeks
  • currently participating in or has participated in another clinical study within the past 12 weeks
  • intends to consume >1.2 liters of grapefruit juice daily during the study
  • is on or likely to require treatment for at least 2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
  • intolerance or hypersensitivity to sitagliptin, simvastatin, metformin or glimepiride
  • is on a weight loss program and not in the maintenance phase or has started a weight loss medication or has undergone bariatric surgery in the previous 12 months
  • has undergone a surgical procedure in the past 4 weeks or planned major surgery during the study
  • has symptomatic hyperglycemia that requires immediate initiation, adjustment, or addition of antihyperglycemic therapy
  • has a history of myopathy or rhabdomyolysis with any statin
  • has cardiovascular disease, a diagnosis of congestive heart failure, or uncontrolled high blood pressure
  • has a history of active liver disease
  • has chronic progressive neuromuscular disorder, human immunodeficiency virus (HIV), hematological disorder, or uncontrolled endocrine or metabolic disease
  • 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
  • has a history of malignancy in the previous 5 years (excluding adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer)
  • is pregnant or breast feeding, or is expecting to conceive or donate eggs during the course of the study, including 14 days after the last dose of study drug
  • is a user of recreational or illicit drugs or has had a recent history of drug abuse
  • 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 3

    Arm Type

    Experimental

    Active Comparator

    Active Comparator

    Arm Label

    Sitagliptin/Simvastatin FDC

    Sitagliptin

    Simvastatin

    Arm Description

    Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.

    Outcomes

    Primary Outcome Measures

    Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary outcome measures.
    Number of Participants Who Experienced at Least One Adverse Event (AE)
    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
    Number of Participants Who Discontinued Study Drug Due to an Adverse Event
    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

    Secondary Outcome Measures

    Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. simvastatin. Results for sitagliptin are presented above under primary outcome measures.
    Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16
    Change from baseline reflects the Week 16 value minus the Week 0 value.
    Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Percent Change From Baseline in Total Cholesterol (TC) at Week 16
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Percent Change From Baseline in Triglycerides (TG) at Week 16
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Percentage of Participants With A1C Level <7% at Week 16
    Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment. Data as observed.

    Full Information

    First Posted
    August 31, 2012
    Last Updated
    July 25, 2018
    Sponsor
    Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT01678820
    Brief Title
    A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)
    Official Title
    A Phase III, Randomized, Double-blind, Clinical Trial to Study the Efficacy and Safety of MK-0431D (a Fixed-dose Combination [FDC] of Sitagliptin and Simvastatin) for the Treatment of Patients With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Terminated
    Why Stopped
    Merck terminated the study for business reasons in November 2013.
    Study Start Date
    October 10, 2012 (Actual)
    Primary Completion Date
    November 1, 2013 (Actual)
    Study Completion Date
    November 1, 2013 (Actual)

    3. Sponsor/Collaborators

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

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to assess the efficacy and safety of sitagliptin/simvastatin fixed-dose combination (FDC) in participants with T2DM who have inadequate glycemic control while on metformin monotherapy. The primary hypothesis of this study is that after 16 weeks of therapy, the mean change from baseline in hemoglobin A1C (A1C) in participants treated with sitagliptin/simvastatin FDC is non-inferior compared to sitagliptin alone.

    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
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    299 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Sitagliptin/Simvastatin FDC
    Arm Type
    Experimental
    Arm Description
    Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
    Arm Title
    Sitagliptin
    Arm Type
    Active Comparator
    Arm Description
    Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
    Arm Title
    Simvastatin
    Arm Type
    Active Comparator
    Arm Description
    Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
    Intervention Type
    Drug
    Intervention Name(s)
    Sitagliptin/Simvastatin FDC
    Other Intervention Name(s)
    MK-0431D, Juvisync™, Juvicor®
    Intervention Description
    Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Sitagliptin
    Other Intervention Name(s)
    MK-0431, Januvia®, Tesavel®, Xelevia®, Ristaben®
    Intervention Description
    Sitagliptin 100 mg tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Simvastatin
    Other Intervention Name(s)
    MK-0733, Zocor®
    Intervention Description
    Simvastatin 40 mg tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to sitagliptin
    Intervention Description
    Matching placebo to sitagliptin 100 mg tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to simvastatin
    Intervention Description
    Matching placebo to simvastatin 40 mg tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to Sitagliptin/Simvastatin FDC
    Intervention Description
    Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin
    Other Intervention Name(s)
    Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
    Intervention Description
    Participants will continue on their stable, pre-screening metformin daily dose of >= 1500 mg for at least 12 weeks prior to randomization and during the study
    Intervention Type
    Drug
    Intervention Name(s)
    Glimepiride
    Other Intervention Name(s)
    Amaryl®, Glimy
    Intervention Description
    Following randomization, participants requiring glycemic rescue may receive open-label glimepiride initiated at a dose of 1 mg/day or 2 mg/day which may be up-titrated to 6 mg/day taken once daily with breakfast or the first main meal of the day.
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)
    Description
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary outcome measures.
    Time Frame
    Baseline and Week 16
    Title
    Number of Participants Who Experienced at Least One Adverse Event (AE)
    Description
    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
    Time Frame
    Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs
    Title
    Number of Participants Who Discontinued Study Drug Due to an Adverse Event
    Description
    Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
    Time Frame
    Up to 16 weeks
    Secondary Outcome Measure Information:
    Title
    Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)
    Description
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. simvastatin. Results for sitagliptin are presented above under primary outcome measures.
    Time Frame
    Baseline and Week 16
    Title
    Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16
    Description
    Change from baseline reflects the Week 16 value minus the Week 0 value.
    Time Frame
    Baseline and Week 16
    Title
    Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16
    Description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Time Frame
    Baseline and Week 16
    Title
    Percent Change From Baseline in Total Cholesterol (TC) at Week 16
    Description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Time Frame
    Baseline and Week 16
    Title
    Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16
    Description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Time Frame
    Baseline and Week 16
    Title
    Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16
    Description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Time Frame
    Baseline and Week 16
    Title
    Percent Change From Baseline in Triglycerides (TG) at Week 16
    Description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Time Frame
    Baseline and Week 16
    Title
    Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16
    Description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Time Frame
    Baseline and Week 16
    Title
    Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16
    Description
    Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
    Time Frame
    Baseline and Week 16
    Title
    Percentage of Participants With A1C Level <7% at Week 16
    Description
    Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment. Data as observed.
    Time Frame
    Week 16

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    79 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: has T2DM (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 14 days after the last dose of study drug is currently on metformin monotherapy at a daily dose of at least 1500 mg for at least 10 weeks is not on a lipid-lowering agent for at least 6 weeks prior to entering the study Exclusion Criteria: has history of type 1 diabetes mellitus (T1DM), or a history of ketoacidosis or possibly has T1DM has been on a thiazolidinedione (TZD) within the previous 16 weeks has been treated with a statin or other lipid-lowering agent (including over-the-counter [OTC] supplements) within the previous 6 weeks currently participating in or has participated in another clinical study within the past 12 weeks intends to consume >1.2 liters of grapefruit juice daily during the study is on or likely to require treatment for at least 2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted) intolerance or hypersensitivity to sitagliptin, simvastatin, metformin or glimepiride is on a weight loss program and not in the maintenance phase or has started a weight loss medication or has undergone bariatric surgery in the previous 12 months has undergone a surgical procedure in the past 4 weeks or planned major surgery during the study has symptomatic hyperglycemia that requires immediate initiation, adjustment, or addition of antihyperglycemic therapy has a history of myopathy or rhabdomyolysis with any statin has cardiovascular disease, a diagnosis of congestive heart failure, or uncontrolled high blood pressure has a history of active liver disease has chronic progressive neuromuscular disorder, human immunodeficiency virus (HIV), hematological disorder, or uncontrolled endocrine or metabolic disease 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 has a history of malignancy in the previous 5 years (excluding adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer) is pregnant or breast feeding, or is expecting to conceive or donate eggs during the course of the study, including 14 days after the last dose of study drug is a user of recreational or illicit drugs or has had a recent history of drug abuse 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

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=0431D-266&kw=0431D-266&tab=access

    Learn more about this trial

    A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)

    We'll reach out to this number within 24 hrs