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)

NCT ID: NCT01678820

Last Updated: 2018-08-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 299 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-10
• Study Completion Date: 2013-11-01

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sitagliptin/Simvastatin FDC

Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. 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.

Group Type: EXPERIMENTAL

Sitagliptin/Simvastatin FDC

Intervention Type: DRUG

Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet

Placebo to sitagliptin

Intervention Type: DRUG

Matching placebo to sitagliptin 100 mg tablet

Placebo to simvastatin

Intervention Type: DRUG

Matching placebo to simvastatin 40 mg tablet

Metformin

Intervention Type: DRUG

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

Glimepiride

Intervention Type: DRUG

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.

Sitagliptin

Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. 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.

Group Type: ACTIVE_COMPARATOR

Sitagliptin

Intervention Type: DRUG

Sitagliptin 100 mg tablet

Placebo to simvastatin

Intervention Type: DRUG

Matching placebo to simvastatin 40 mg tablet

Placebo to Sitagliptin/Simvastatin FDC

Intervention Type: DRUG

Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet

Metformin

Intervention Type: DRUG

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

Glimepiride

Intervention Type: DRUG

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.

Simvastatin

Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. 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.

Group Type: ACTIVE_COMPARATOR

Simvastatin

Intervention Type: DRUG

Simvastatin 40 mg tablet

Placebo to sitagliptin

Intervention Type: DRUG

Matching placebo to sitagliptin 100 mg tablet

Placebo to Sitagliptin/Simvastatin FDC

Intervention Type: DRUG

Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet

Metformin

Intervention Type: DRUG

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

Glimepiride

Intervention Type: DRUG

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.

Interventions

Sitagliptin/Simvastatin FDC

Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet

Intervention Type: DRUG

Sitagliptin

Sitagliptin 100 mg tablet

Intervention Type: DRUG

Simvastatin

Simvastatin 40 mg tablet

Intervention Type: DRUG

Placebo to sitagliptin

Matching placebo to sitagliptin 100 mg tablet

Intervention Type: DRUG

Placebo to simvastatin

Matching placebo to simvastatin 40 mg tablet

Intervention Type: DRUG

Placebo to Sitagliptin/Simvastatin FDC

Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

MK-0431D; Juvisync™; Juvicor®; MK-0431; Januvia®; Tesavel®; Xelevia®; Ristaben®; MK-0733; Zocor®; Fortamet®; Glucophage®; Glucophage® XR; Glumetza®; Riomet®; Metgluco®; Glycoran®; Amaryl®; Glimy

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

0431D-266

Identifier Type: -

Identifier Source: org_study_id