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)

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01678820
• Other study ID #: 0431D-266
• Status: Terminated
• Phase: Phase 3
• Start date: October 10, 2012
• Est. completion date: November 1, 2013

Study information

• Verified date: July 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 299
• Est. completion date: November 1, 2013
• Est. primary completion date: November 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sitagliptin/Simvastatin FDC
Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet
• Sitagliptin
Sitagliptin 100 mg tablet
• Simvastatin
Simvastatin 40 mg tablet
• Placebo to sitagliptin
Matching placebo to sitagliptin 100 mg tablet
• Placebo to simvastatin
Matching placebo to simvastatin 40 mg tablet
• Placebo to Sitagliptin/Simvastatin FDC
Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet
• 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
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)	A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary outcome measures.	Baseline and Week 16
Primary	Number of Participants Who Experienced at Least One Adverse Event (AE)	Excludes data after rescue therapy. 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 16 weeks for non-serious AEs, up to 18 weeks for serious AEs
Primary	Number of Participants Who Discontinued Study Drug Due to an Adverse Event	Excludes data after rescue therapy. 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 16 weeks
Secondary	Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)	A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. simvastatin. Results for sitagliptin are presented above under primary outcome measures.	Baseline and Week 16
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16	Change from baseline reflects the Week 16 value minus the Week 0 value.	Baseline and Week 16
Secondary	Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Total Cholesterol (TC) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Triglycerides (TG) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16	Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.	Baseline and Week 16
Secondary	Percentage of Participants With A1C Level <7% at Week 16	Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment. Data as observed.	Week 16