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)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin/Simvastatin FDC; Sitagliptin; Simvastatin; Placebo to sitagliptin; Placebo to simvastatin; Placebo to Sitagliptin/Simvastatin FDC; Metformin; Glimepiride
Intervention description: Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet; Sitagliptin 100 mg tablet; Simvastatin 40 mg tablet; Matching placebo to sitagliptin 100 mg tablet; Matching placebo to simvastatin 40 mg tablet; Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet; 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; 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.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Glimepiride; Simvastatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 299.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No

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.
    

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