A Study to Assess the Safety and Tolerability of Sitagliptin/Simvastatin Fixed-dose Combination (FDC) in Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-312)

Study Overview
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Brief Summary
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The purpose of this study is to examine the safety and tolerability of sitagliptin 100 mg/simvastatin 40 mg FDC (MK-0431D) in Vietnamese participants with type 2 diabetes mellitus with inadequate glycemic control on metformin.

Official Title
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An Open-label Study to Assess the Safety and Tolerability of MK-0431D for the Treatment of Patients With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin 100 mg/simvastatin 40 mg FDC
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has type 2 diabetes mellitus Male, or female who is not of reproductive potential or if of reproductive potential agrees to abstain or use (or have their partner use) two acceptable methods of birth control during the study and for 14 days after the last dose of study drug Currently on metformin monotherapy (>=1000 mg per day) for at least 4 weeks prior to study participation Not on statin therapy or other lipid-lowering agent for at least 6 weeks prior to study participation Exclusion Criteria: History of type 1 diabetes mellitus or a history of ketoacidosis History of 2 or more episodes of hypoglycemia resulting in seizure, coma or loss of consciousness over the past 3 months On a thiazolidinedione (TZD) within the past 12 weeks Has been treated with a statin or other lipid-lowering agent within 6 weeks prior to study participation Is on or likely to require treatment with a prohibited medication (itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol, amiodarone, verapamil, diltiazem, amlodipine, ranolazine, niacin) Intends to consume >1.2 liters of grapefruit juice per day during the study Is on or likely to require treatment for >=2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted) Is on a weight loss program and not in the maintenance phase or has started a weight loss medication or has undergone bariatric surgery within 12 months prior to study participation Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study History of myopathy or rhabdomyolysis with any statin History of myocardial infarction, unstable or stable angina, angioplasty, bypass surgery, myocardial ischemia, peripheral artery disease, abdominal aortic aneurysm, transient ischemic attacks, stroke of carotid origin or >50% obstruction of a carotid artery Diagnosis of congestive heart failure with New York Heart Association (NYHA) Class III or IV cardiac status History of active liver disease (other than non-alcoholic steatosis) including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease Chronic progressive neuromuscular disorder Human immunodeficiency virus (HIV) Hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia) Currently being treated for hyperthyroidism or is on thyroid hormone replacement therapy and has not been on a stable dose for at least 6 weeks History of malignancy <=5 years prior to study participation, except for basal cell or squamous cell skin cancer or in situ cervical cancer Positive urine pregnancy test Pregnant or breastfeeding, or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug User of recreational or illicit drugs or has had a recent history of drug abuse Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin 100 mg/simvastatin 40 mg FDC<br>Sitagliptin 100 mg/simvastatin 40 mg FDC once daily in the evening for 6 weeks. Participants will continue pre-study dose of metformin >=1000 mg per day. | Drug: Sitagliptin 100 mg/simvastatin 40 mg FDC<br>* Sitagliptin 100 mg/simvastatin 40 mg FDC tablet administered once daily in the evening for 6 weeks<br>* Other names: MK-0431D;Drug: Metformin<br>* Participants will continue pre-study dose of metformin tablet(s) >=1000 per day<br>* Other names: Glycoran®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Change from baseline in FPG at Week 6 based on longitudinal data analysis (LDA) model including both baseline and post-baseline measurements as response variable and term time. | Baseline and Week 6 | 
| Percentage 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 Sponsor's product, whether or not considered related to the use of the product. | Up to 8 weeks (including 14 days after final dose of study drug) | 
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Participants who were discontinued from study drug due to an adverse event during the 6 weeks of treatment. | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | Change from baseline in LDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. | Baseline and Week 6 | 
| Change From Baseline in Total Cholesterol (TC) | Change from baseline in TC was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. | Baseline and Week 6 | 
| Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) | Change from baseline in non-HDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. | Baseline and Week 6 | 
| Change From Baseline in Triglycerides (TG) | Change from baseline in TG was measured as a percent change from baseline at Week 6 (median and distribution free 95% confidence interval). | Baseline and Week 6 | 
| Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) | Change from baseline in HDL-C was measured as a percent change from baseline at Week 6 based on LDA model including percent change from baseline as response variable and term time. | Baseline and Week 6 |