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)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 3

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Glimepiride; Drug: Simvastatin; Drug: Placebo to Sitagliptin/Simvastatin FDC; Drug: Placebo to simvastatin; Drug: Metformin; Drug: Placebo to sitagliptin; Drug: Sitagliptin; Drug: Sitagliptin/Simvastatin FDC

Study type: Interventional

Funder types: Industry

Identifiers

NCT01678820

0431D-266

Details and patient eligibility

About

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.

Enrollment: 299 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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299 participants in 3 patient groups

Sitagliptin/Simvastatin FDC

Experimental group

Description:

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.

Treatment:

Drug: Placebo to sitagliptin

Drug: Sitagliptin/Simvastatin FDC

Drug: Placebo to simvastatin

Drug: Glimepiride

Drug: Metformin

Sitagliptin

Active Comparator group

Description:

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.

Treatment:

Drug: Sitagliptin

Drug: Placebo to Sitagliptin/Simvastatin FDC

Drug: Placebo to simvastatin

Drug: Glimepiride

Drug: Metformin

Simvastatin

Active Comparator group

Description:

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.

Treatment:

Drug: Placebo to sitagliptin

Drug: Placebo to Sitagliptin/Simvastatin FDC

Drug: Simvastatin

Drug: Glimepiride

Drug: Metformin