- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01678820
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)
July 25, 2018 updated by: Merck Sharp & Dohme LLC
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
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.
Study Overview
Status
Terminated
Conditions
Study Type
Interventional
Enrollment (Actual)
299
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 79 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
Sitagliptin 100 mg/Simvastatin 40 mg fixed-dose combination tablet
Other Names:
Matching placebo to sitagliptin 100 mg tablet
Matching placebo to simvastatin 40 mg tablet
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:
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:
|
Active Comparator: 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.
|
Matching placebo to simvastatin 40 mg tablet
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:
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:
Sitagliptin 100 mg tablet
Other Names:
Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet
|
Active Comparator: 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.
|
Matching placebo to sitagliptin 100 mg tablet
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:
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:
Matching placebo to sitagliptin 100 mg/simvastatin 40 mg FDC tablet
Simvastatin 40 mg tablet
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)
Time Frame: Baseline and Week 16
|
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
|
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
|
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
|
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Time Frame: Up to 16 weeks
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)
Time Frame: Baseline and Week 16
|
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
|
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16
Time Frame: Baseline and Week 16
|
Change from baseline reflects the Week 16 value minus the Week 0 value.
|
Baseline and Week 16
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16
Time Frame: Baseline and 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
|
Percent Change From Baseline in Total Cholesterol (TC) at Week 16
Time Frame: Baseline and 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
|
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16
Time Frame: Baseline and 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
|
Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16
Time Frame: Baseline and 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
|
Percent Change From Baseline in Triglycerides (TG) at Week 16
Time Frame: Baseline and 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
|
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16
Time Frame: Baseline and 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
|
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16
Time Frame: Baseline and 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
|
Percentage of Participants With A1C Level <7% at Week 16
Time Frame: Week 16
|
Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment.
Data as observed.
|
Week 16
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 10, 2012
Primary Completion (Actual)
November 1, 2013
Study Completion (Actual)
November 1, 2013
Study Registration Dates
First Submitted
August 31, 2012
First Submitted That Met QC Criteria
August 31, 2012
First Posted (Estimate)
September 5, 2012
Study Record Updates
Last Update Posted (Actual)
August 24, 2018
Last Update Submitted That Met QC Criteria
July 25, 2018
Last Verified
July 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Enzyme Inhibitors
- Antimetabolites
- Immunosuppressive Agents
- Immunologic Factors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protease Inhibitors
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Incretins
- Dipeptidyl-Peptidase IV Inhibitors
- Metformin
- Sitagliptin Phosphate
- Glimepiride
- Simvastatin
Other Study ID Numbers
- 0431D-266
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study Data/Documents
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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