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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)

This study has been terminated.
(Merck terminated the study for business reasons in November 2013.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01678820
First received: August 31, 2012
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Sitagliptin/Simvastatin FDC
Drug: Sitagliptin
Drug: Simvastatin
Drug: Placebo to sitagliptin
Drug: Placebo to simvastatin
Drug: Placebo to Sitagliptin/Simvastatin FDC
Drug: Metformin
Drug: Glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin) [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment. Data as observed.


Enrollment: 299
Study Start Date: October 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin/Simvastatin FDC
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.
Drug: Sitagliptin/Simvastatin FDC
Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet
Other Names:
  • MK-0431D
  • Juvisync™
  • Juvicor®
Drug: Placebo to sitagliptin
Matching placebo to sitagliptin 100 mg tablet
Drug: Placebo to simvastatin
Matching placebo to simvastatin 40 mg tablet
Drug: Metformin
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
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Glimepiride
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.
Other Names:
  • Amaryl®
  • Glimy
Active Comparator: Sitagliptin
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.
Drug: Sitagliptin
Sitagliptin 100 mg tablet
Other Names:
  • MK-0431
  • Januvia®
  • Tesavel®
  • Xelevia®
  • Ristaben®
Drug: Placebo to simvastatin
Matching placebo to simvastatin 40 mg tablet
Drug: Placebo to Sitagliptin/Simvastatin FDC
Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet
Drug: Metformin
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
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Glimepiride
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.
Other Names:
  • Amaryl®
  • Glimy
Active Comparator: Simvastatin
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.
Drug: Simvastatin
Simvastatin 40 mg tablet
Other Names:
  • MK-0733
  • Zocor®
Drug: Placebo to sitagliptin
Matching placebo to sitagliptin 100 mg tablet
Drug: Placebo to Sitagliptin/Simvastatin FDC
Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet
Drug: Metformin
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
Other Names:
  • Fortamet®
  • Glucophage®
  • Glucophage® XR
  • Glumetza®
  • Riomet®
  • Metgluco®
  • Glycoran®
Drug: Glimepiride
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.
Other Names:
  • Amaryl®
  • Glimy

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01678820

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: NCT01678820     History of Changes
Other Study ID Numbers: 0431D-266
Study First Received: August 31, 2012
Results First Received: October 16, 2014
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Glimepiride
Metformin
Simvastatin
Sitagliptin
Anti-Arrhythmia Agents
Anticholesteremic Agents
Antimetabolites
Cardiovascular Agents
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypoglycemic Agents
Hypolipidemic Agents
Immunologic Factors
Immunosuppressive Agents
Incretins
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014