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)

NCT01678820 | Terminated Phase 3 Results

• 1 other identifier: 0431D-266
• Study Type: interventional
• Target: 299
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (10)

• Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)

  Baseline and Week 16

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16

  Baseline and Week 16

• Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16

  Baseline and Week 16

• Percent Change From Baseline in Total Cholesterol (TC) at Week 16

  Baseline and Week 16

• Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16

  Baseline and Week 16

Study Arms (3)

Sitagliptin/Simvastatin FDC

EXPERIMENTAL

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.

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

Sitagliptin

ACTIVE COMPARATOR

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.

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

Simvastatin

ACTIVE COMPARATOR

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.

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

Interventions

Sitagliptin/Simvastatin FDC DRUG

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

Also known as: MK-0431D, Juvisync™, Juvicor®

Sitagliptin/Simvastatin FDC

Sitagliptin DRUG

Sitagliptin 100 mg tablet

Also known as: MK-0431, Januvia®, Tesavel®, Xelevia®, Ristaben®

Sitagliptin

Simvastatin DRUG

Simvastatin 40 mg tablet

Also known as: MK-0733, Zocor®

Simvastatin

Placebo to sitagliptin DRUG

Matching placebo to sitagliptin 100 mg tablet

Simvastatin; Sitagliptin/Simvastatin FDC

Placebo to simvastatin DRUG

Matching placebo to simvastatin 40 mg tablet

Sitagliptin; Sitagliptin/Simvastatin FDC

Placebo to Sitagliptin/Simvastatin FDC DRUG

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

Simvastatin; Sitagliptin

Metformin 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

Also known as: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®

Simvastatin; Sitagliptin; Sitagliptin/Simvastatin FDC

Glimepiride 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.

Also known as: Amaryl®, Glimy

Simvastatin; Sitagliptin; Sitagliptin/Simvastatin FDC

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; Simvastatin; Metformin; glimepiride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Biguanides; Guanidines; Amidines

Limitations and Caveats

Study was terminated for business reasons in November 2013.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2012
• First Posted: September 5, 2012
• Study Start: October 10, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: August 24, 2018
• Results First Posted: October 22, 2014

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share