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) | RxWiki

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)

Overview[ - collapse ][ - ]

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	Type 2 Diabetes Mellitus
Intervention	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	Phase 3
Sponsor	Merck Sharp & Dohme Corp.
Responsible Party	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier	NCT01678820
First Received	August 31, 2012
Last Updated	November 25, 2013
Last verified	November 2013

Tracking Information[ + expand ][ + ]

First Received Date	August 31, 2012
Last Updated Date	November 25, 2013
Start Date	October 2012
Estimated Primary Completion Date	November 2013
Current 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] 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]
Current Secondary Outcome Measures	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]

Descriptive Information[ + expand ][ + ]

Brief Title	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)
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
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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Condition	Type 2 Diabetes Mellitus
Intervention	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
Study Arm (s)	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. 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. 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.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Terminated
Estimated Enrollment	297
Estimated Completion Date	November 2013
Estimated Primary Completion Date	November 2013
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 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
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	Not Provided

Administrative Information[ + expand ][ + ]

NCT Number	NCT01678820
Other Study ID Numbers	0431D-266
Has Data Monitoring Committee	No
Information Provided By	Merck Sharp & Dohme Corp.
Study Sponsor	Merck Sharp & Dohme Corp.
Collaborators	Not Provided
Investigators	Not Provided
Verification Date	November 2013