Clinical trial NCT01678820: 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
Overall status: TERMINATED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-09-05
Enrollment: 299
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)
timeFrame: Baseline and Week 16
measure: Number of Participants Who Experienced at Least One Adverse Event (AE)
timeFrame: Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs
measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to 16 weeks
Secondary outcomes:
measure: Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)
timeFrame: Baseline and Week 16
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Total Cholesterol (TC) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Triglycerides (TG) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16
timeFrame: Baseline and Week 16
measure: Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants With A1C Level <7% at Week 16
timeFrame: Week 16
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: