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A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)

Primary Purpose

Type 2 Diabetes Mellitus

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sitagliptin
Atorvastatin
Placebo to sitagliptin
Placebo to atorvastatin
Metformin (open-label)
Glimepiride (open-label)
Glimepiride (double-blind)
Placebo to 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 type 2 diabetes mellitus
  • is a male, or a female who is highly unlikely to conceive
  • is currently on monotherapy with metformin (at least 1500 mg/day) for at least 8 weeks
  • is not on statin therapy or other lipid-lowering agents for at least 6 weeks

Exclusion Criteria:

  • has a history of type 1 diabetes mellitus, ketoacidosis or possibly has type 1 diabetes
  • has ever taken a dipeptidyl peptidase IV inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or a glucagon-like peptide-1 mimetic (such as exenatide or liraglutide), or has required insulin therapy within 12 weeks prior to signing informed consent
  • has been on a peroxisome proliferator-activated receptor gamma agonist within the prior 12 weeks
  • has been treated with a statin or other lipid-lowering agents, including over the counter supplements of fish oils within 6 weeks
  • intends to consume at least 1.2 liters of grapefruit juice per day during the course of the study
  • is on or is likely to require treatment with 14 consecutive days or more, or repeated courses of corticosteroids
  • is on a weight loss program and not in the maintenance phase or has started a weight loss medication (such as orlistat or sibutramine) within the prior 8 weeks
  • has undergone a surgical procedure within the prior 4 weeks
  • has a history of myopathy or rhabdomyolysis with any statin.
  • has cardiovascular disease
  • has New York Heart Association (NYHA) Class III or IV congestive heart failure, inadequately controlled hypertension, a medical history of active liver disease, chronic progressive neuromuscular disorder, is human immunodeficiency virus (HIV) positive, has a clinically significant hematological disorder, uncontrolled endocrine or metabolic disease known to influence glycemic control or serum lipids/lipoproteins, untreated hyperthyroidism or is currently under treatment for hyperthyroidism
  • has a history of malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
  • is pregnant or breastfeeding, or is intending to become pregnant or donate eggs within the projected duration of the study and post-study follow-up period
  • uses recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or increased alcohol consumption

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Active Comparator

    Experimental

    Arm Label

    Sitagliptin/Sitagliptin + Atorvastatin

    Atorvastatin/Atorvastatin + Glimepiride

    Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin

    Arm Description

    In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.

    In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.

    In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.

    Outcomes

    Primary Outcome Measures

    Change From Baseline in Hemoglobin A1C (A1C) at Week 16
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.
    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%.
    Number of Participants Who Experienced at Least One Adverse Event
    An 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 investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.
    Number of Participants Who Discontinued Study Drug Due to an Adverse Event
    An 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 investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.

    Secondary 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 Total Cholesterol 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 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%.
    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%.

    Full Information

    First Posted
    November 19, 2011
    Last Updated
    July 25, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01477853
    Brief Title
    A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)
    Official Title
    A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Co-administration of Sitagliptin and Atorvastatin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Terminated
    Why Stopped
    The study was terminated early by the Sponsor for business reasons.
    Study Start Date
    October 24, 2011 (Actual)
    Primary Completion Date
    December 4, 2012 (Actual)
    Study Completion Date
    December 4, 2012 (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
    This two-phase study was to examine if 16 weeks of treatment with sitagliptin in combination with atorvastatin reduces hemoglobin A1C (A1C) and low density lipoprotein cholesterol (LDL-C) from baseline more than atorvastatin alone and sitagliptin alone, respectively. Following a single-blind placebo run-in period, participants were to be randomized to one of three treatment arms (sitagliptin monotherapy, atorvastatin monotherapy, or sitagliptin plus atorvastatin) for 16 weeks (Phase A). During Phase B of the study (Weeks 16 through 54), participants were to receive either sitagliptin plus atorvastatin or glimepiride plus atorvastatin. The primary hypotheses were that after 16 weeks of treatment, sitagliptin in combination with atorvastatin reduces A1C from baseline more than atorvastatin alone, and that atorvastatin in combination with sitagliptin lowers LDL-C from baseline more than 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
    166 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Sitagliptin/Sitagliptin + Atorvastatin
    Arm Type
    Experimental
    Arm Description
    In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
    Arm Title
    Atorvastatin/Atorvastatin + Glimepiride
    Arm Type
    Active Comparator
    Arm Description
    In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.
    Arm Title
    Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
    Arm Type
    Experimental
    Arm Description
    In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
    Intervention Type
    Drug
    Intervention Name(s)
    Sitagliptin
    Other Intervention Name(s)
    Januvia
    Intervention Description
    Sitagliptin 100 mg tablet orally daily
    Intervention Type
    Drug
    Intervention Name(s)
    Atorvastatin
    Other Intervention Name(s)
    Lipitor
    Intervention Description
    Atorvastatin 80 mg tablet orally daily
    Intervention Type
    Other
    Intervention Name(s)
    Placebo to sitagliptin
    Intervention Description
    Placebo to sitagliptin tablet orally daily
    Intervention Type
    Other
    Intervention Name(s)
    Placebo to atorvastatin
    Intervention Description
    Placebo to atorvastatin tablet orally daily.
    Intervention Type
    Drug
    Intervention Name(s)
    Metformin (open-label)
    Other Intervention Name(s)
    Glucophage
    Intervention Description
    Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.
    Intervention Type
    Drug
    Intervention Name(s)
    Glimepiride (open-label)
    Other Intervention Name(s)
    Amaryl
    Intervention Description
    Phase A: Glimepiride 1 or 2 mg tablet once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals.
    Intervention Type
    Drug
    Intervention Name(s)
    Glimepiride (double-blind)
    Intervention Description
    Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo to glimepiride
    Intervention Description
    Phase B: placebo to glimepiride tablet orally daily.
    Primary Outcome Measure Information:
    Title
    Change From Baseline in Hemoglobin A1C (A1C) at Week 16
    Description
    A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent.
    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
    Number of Participants Who Experienced at Least One Adverse Event
    Description
    An 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 investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.
    Time Frame
    Up to 56 weeks (including 2-week follow-up)
    Title
    Number of Participants Who Discontinued Study Drug Due to an Adverse Event
    Description
    An 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 investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.
    Time Frame
    Up to 54 weeks
    Secondary Outcome Measure Information:
    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 Total Cholesterol 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 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
    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

    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 type 2 diabetes mellitus is a male, or a female who is highly unlikely to conceive is currently on monotherapy with metformin (at least 1500 mg/day) for at least 8 weeks is not on statin therapy or other lipid-lowering agents for at least 6 weeks Exclusion Criteria: has a history of type 1 diabetes mellitus, ketoacidosis or possibly has type 1 diabetes has ever taken a dipeptidyl peptidase IV inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or a glucagon-like peptide-1 mimetic (such as exenatide or liraglutide), or has required insulin therapy within 12 weeks prior to signing informed consent has been on a peroxisome proliferator-activated receptor gamma agonist within the prior 12 weeks has been treated with a statin or other lipid-lowering agents, including over the counter supplements of fish oils within 6 weeks intends to consume at least 1.2 liters of grapefruit juice per day during the course of the study is on or is likely to require treatment with 14 consecutive days or more, or repeated courses of corticosteroids is on a weight loss program and not in the maintenance phase or has started a weight loss medication (such as orlistat or sibutramine) within the prior 8 weeks has undergone a surgical procedure within the prior 4 weeks has a history of myopathy or rhabdomyolysis with any statin. has cardiovascular disease has New York Heart Association (NYHA) Class III or IV congestive heart failure, inadequately controlled hypertension, a medical history of active liver disease, chronic progressive neuromuscular disorder, is human immunodeficiency virus (HIV) positive, has a clinically significant hematological disorder, uncontrolled endocrine or metabolic disease known to influence glycemic control or serum lipids/lipoproteins, untreated hyperthyroidism or is currently under treatment for hyperthyroidism has a history of malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer is pregnant or breastfeeding, or is intending to become pregnant or donate eggs within the projected duration of the study and post-study follow-up period uses recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or increased alcohol consumption
    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

    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=0431E-211&kw=0431E-211&tab=access

    Learn more about this trial

    A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)

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