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 AM1)

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: November 25, 2013
Last verified: November 2013

August 31, 2012
November 25, 2013
October 2012
November 2013   (final data collection date for primary outcome measure)
  • 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 ]
  • 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 ]
  • Number of participants who discontinued from the study due to an adverse event [ Time Frame: up to 16 weeks ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01678820 on ClinicalTrials.gov Archive Site
  • Change from baseline in hemoglobin A1C (A1C) at Week 16 (sitagliptin/simvastatin FDC vs. simvastatin) [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • 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 in low-density lipoprotein cholesterol (LDL-C) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Change from baseline in total cholesterol (TC) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Change from baseline in apolipoprotein B (Apo B) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • 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 ]
  • Change from baseline in triglycerides (TG) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • Change from baseline in high-density lipoprotein cholesterol (HDL-C) at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
  • 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 ]
  • Proportion of participants with A1C level <7% at Week 16 [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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 AM1)
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Type 2 Diabetes Mellitus
  • Drug: Sitagliptin/Simvastatin FDC
    Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet
    Other Names:
    • MK-0431D
    • Juvisync™
    • Juvicor®
  • Drug: Sitagliptin
    Sitagliptin 100 mg tablet
    Other Names:
    • MK-0431
    • Januvia®
    • Tesavel®
    • Xelevia®
    • Ristaben®
  • 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 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
  • Experimental: Sitagliptin/Simvastatin FDC
    Sitagliptin 100 mg/simvastatin 40 mg FDC (fixed-dose combination) plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. 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.
    Interventions:
    • Drug: Sitagliptin/Simvastatin FDC
    • Drug: Placebo to sitagliptin
    • Drug: Placebo to simvastatin
    • Drug: Metformin
    • Drug: Glimepiride
  • Active Comparator: Sitagliptin
    Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. 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.
    Interventions:
    • Drug: Sitagliptin
    • Drug: Placebo to simvastatin
    • Drug: Placebo to Sitagliptin/Simvastatin FDC
    • Drug: Metformin
    • Drug: Glimepiride
  • Active Comparator: Simvastatin
    Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. 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.
    Interventions:
    • Drug: Simvastatin
    • Drug: Placebo to sitagliptin
    • Drug: Placebo to Sitagliptin/Simvastatin FDC
    • Drug: Metformin
    • Drug: Glimepiride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
297
November 2013
November 2013   (final data collection date for primary outcome measure)

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 over 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
Both
18 Years to 79 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01678820
0431D-266
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP