A Study of the Co-administration of Sitagliptin and Atorvastatin in Inadequately Controlled Type 2 Diabetes Mellitus (MK-0431E-211)

NCT ID: NCT01477853

Last Updated: 2018-07-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-24
• Study Completion Date: 2012-12-04

Brief Summary

This two-phase study was to examine if 16 weeks of treatment with sitagliptin in combination with atorvastatin reduces hemoglobin A1C (A1C) and low density lipoprotein cholesterol (LDL-C) from baseline more than atorvastatin alone and sitagliptin alone, respectively. Following a single-blind placebo run-in period, participants were to be randomized to one of three treatment arms (sitagliptin monotherapy, atorvastatin monotherapy, or sitagliptin plus atorvastatin) for 16 weeks (Phase A). During Phase B of the study (Weeks 16 through 54), participants were to receive either sitagliptin plus atorvastatin or glimepiride plus atorvastatin. The primary hypotheses were that after 16 weeks of treatment, sitagliptin in combination with atorvastatin reduces A1C from baseline more than atorvastatin alone, and that atorvastatin in combination with sitagliptin lowers LDL-C from baseline more than 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/Sitagliptin + Atorvastatin

In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

Sitagliptin 100 mg tablet orally daily

Atorvastatin

Intervention Type: DRUG

Atorvastatin 80 mg tablet orally daily

Placebo to atorvastatin

Intervention Type: OTHER

Placebo to atorvastatin tablet orally daily.

Metformin (open-label)

Intervention Type: DRUG

Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.

Glimepiride (open-label)

Intervention Type: DRUG

Phase A: Glimepiride 1 or 2 mg tablet once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals.

Placebo to glimepiride

Intervention Type: DRUG

Phase B: placebo to glimepiride tablet orally daily.

Atorvastatin/Atorvastatin + Glimepiride

In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.

Group Type: ACTIVE_COMPARATOR

Atorvastatin

Intervention Type: DRUG

Atorvastatin 80 mg tablet orally daily

Placebo to sitagliptin

Intervention Type: OTHER

Placebo to sitagliptin tablet orally daily

Metformin (open-label)

Intervention Type: DRUG

Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.

Glimepiride (double-blind)

Intervention Type: DRUG

Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.

Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin

In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

Sitagliptin 100 mg tablet orally daily

Atorvastatin

Intervention Type: DRUG

Atorvastatin 80 mg tablet orally daily

Metformin (open-label)

Intervention Type: DRUG

Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.

Glimepiride (open-label)

Intervention Type: DRUG

Phase A: Glimepiride 1 or 2 mg tablet once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals.

Placebo to glimepiride

Intervention Type: DRUG

Phase B: placebo to glimepiride tablet orally daily.

Interventions

Sitagliptin

Sitagliptin 100 mg tablet orally daily

Intervention Type: DRUG

Atorvastatin

Atorvastatin 80 mg tablet orally daily

Intervention Type: DRUG

Placebo to sitagliptin

Placebo to sitagliptin tablet orally daily

Intervention Type: OTHER

Placebo to atorvastatin

Placebo to atorvastatin tablet orally daily.

Intervention Type: OTHER

Metformin (open-label)

Participant will remain on prestudy dose of metformin tablets (at least 1500 mg daily) throughout entire study.

Intervention Type: DRUG

Glimepiride (open-label)

Phase A: Glimepiride 1 or 2 mg tablet once daily with breakfast or the first main meal of the day (titrated up to 6 mg/day) for 16 weeks as rescue therapy for randomized participants not meeting specific glycemic goals.

Intervention Type: DRUG

Glimepiride (double-blind)

Phase B: glimepiride up to 6 mg daily for participants not rescued with open-label glimepiride during Phase A.

Intervention Type: DRUG

Placebo to glimepiride

Phase B: placebo to glimepiride tablet orally daily.

Intervention Type: DRUG

Other Intervention Names

Januvia; Lipitor; Glucophage; Amaryl

Eligibility Criteria

Inclusion Criteria

• has type 2 diabetes mellitus
• is a male, or a female who is highly unlikely to conceive
• is currently on monotherapy with metformin (at least 1500 mg/day) for at least 8 weeks
• is not on statin therapy or other lipid-lowering agents for at least 6 weeks

Exclusion Criteria

• has a history of type 1 diabetes mellitus, ketoacidosis or possibly has type 1 diabetes
• has ever taken a dipeptidyl peptidase IV inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or a glucagon-like peptide-1 mimetic (such as exenatide or liraglutide), or has required insulin therapy within 12 weeks prior to signing informed consent
• has been on a peroxisome proliferator-activated receptor gamma agonist within the prior 12 weeks
• has been treated with a statin or other lipid-lowering agents, including over the counter supplements of fish oils within 6 weeks
• intends to consume at least 1.2 liters of grapefruit juice per day during the course of the study
• is on or is likely to require treatment with 14 consecutive days or more, or repeated courses of corticosteroids
• is on a weight loss program and not in the maintenance phase or has started a weight loss medication (such as orlistat or sibutramine) within the prior 8 weeks
• has undergone a surgical procedure within the prior 4 weeks
• has a history of myopathy or rhabdomyolysis with any statin.
• has cardiovascular disease
• has New York Heart Association (NYHA) Class III or IV congestive heart failure, inadequately controlled hypertension, a medical history of active liver disease, chronic progressive neuromuscular disorder, is human immunodeficiency virus (HIV) positive, has a clinically significant hematological disorder, uncontrolled endocrine or metabolic disease known to influence glycemic control or serum lipids/lipoproteins, untreated hyperthyroidism or is currently under treatment for hyperthyroidism
• has a history of malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
• is pregnant or breastfeeding, or is intending to become pregnant or donate eggs within the projected duration of the study and post-study follow-up period
• uses recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or increased alcohol consumption

• 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

2011-003600-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0431E-211

Identifier Type: -

Identifier Source: org_study_id