Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251)

NCT ID: NCT01189890

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 480 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-16
• Study Completion Date: 2012-10-31

Brief Summary

The primary objectives of this study are to determine if sitagliptin treatment is not inferior to that of glimepiride as measured by the change in baseline hemoglobin A1C (HbA1C) after 30 weeks of treatment, and if sitagliptin treatment results in a lower incidence of symptomatic hypoglycemia compared to that of glimepiride. The study will also evaluate if sitagliptin treatment, compared to glimepiride results in improvements in fasting plasma glucose (FPG) levels, and plasma lipid levels after 30 weeks of treatment. Participants will be randomized to either sitagliptin or glimepiride treatment after eligibility for study participation is determined during screening and washout study phases. Participants and study staff will not know to which treatment group they have been randomized (double-blind design). The duration of study participation will be up to 40 weeks (with 9 clinic visits). This will include a screening phase (Visit 1 to Visit 2) of 2 weeks maximum; a 6-week (Visits 2 to 3) oral antihyperglycemic agent (AHA) wash-out phase (for those who have been taking a AHA prior to the study); a placebo run-in phase (Visits 3 to 4), followed by up to 30 weeks of treatment with study medication.

Detailed Description

The dose of sitagliptin will be 100 mg once daily (QD) or 50 mg QD based on the participant's estimated glomerular filtration rate (eGFR). The starting dose of glimepiride (1 mg QD) may be up-titrated as needed to optimize glycemic control over the first 18 weeks to a maximum dose of 6 mg/day, after which the dose will not be increased for the rest of the study (down-titration to avoid or control hypoglycemia is allowed).

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sitagliptin

Sitagliptin phosphate 100 mg or 50 mg once daily (QD)

Group Type: EXPERIMENTAL

sitagliptin phosphate

Intervention Type: DRUG

Sitagliptin tablets, orally, at a dose of 100 mg or 50 mg QD for 30 weeks. The dose level to be administered will depend on the participant's estimated glomerular filtration rate (eGFR), calculated at Visit 3 and may be adjusted as medically indicated during the study.

Placebo to Glimepiride

Intervention Type: DRUG

Matching placebo tablets to glimepiride to allow for blinding.

Glimepiride

Glimepiride 1-6 mg QD

Group Type: ACTIVE_COMPARATOR

Glimepiride

Intervention Type: DRUG

Glimepiride tablets, orally, starting at a dose of 1 mg QD, which may be gradually increased, as needed, to maximum dose of 6 mg QD for 30 weeks. The dose may also be decreased as medically indicated during the study.

Placebo to Sitagliptin

Intervention Type: DRUG

Matching placebo tablets to sitagliptin to allow for blinding.

Interventions

sitagliptin phosphate

Sitagliptin tablets, orally, at a dose of 100 mg or 50 mg QD for 30 weeks. The dose level to be administered will depend on the participant's estimated glomerular filtration rate (eGFR), calculated at Visit 3 and may be adjusted as medically indicated during the study.

Intervention Type: DRUG

Glimepiride

Glimepiride tablets, orally, starting at a dose of 1 mg QD, which may be gradually increased, as needed, to maximum dose of 6 mg QD for 30 weeks. The dose may also be decreased as medically indicated during the study.

Intervention Type: DRUG

Placebo to Sitagliptin

Matching placebo tablets to sitagliptin to allow for blinding.

Intervention Type: DRUG

Placebo to Glimepiride

Matching placebo tablets to glimepiride to allow for blinding.

Intervention Type: DRUG

Other Intervention Names

Januvia; Amaryl

Eligibility Criteria

Inclusion Criteria

• Diagnosis of type 2 diabetes mellitus

Exclusion Criteria

• History of type 1 diabetes mellitus
• Has undergone a surgical procedure within the prior 4 weeks.
• Current participation in, or has participated, in another study with an investigational device or compound, with the prior 12 weeks, and/or is not willing to refrain from participating in any other study while participating in this study
• Hypersensitivity or contraindication to any sulfonylurea (e.g., glimepiride) medication
• Has been on an investigational or approved dipeptidyl peptidase-4 (DPP-4) inhibitor agent (e.g., sitagliptin, saxagliptin)
• Presence of human immunodeficiency virus (HIV)
• Current participation in a weight loss program or is receiving weight loss medication
• History of blood disorder, certain cancers, heart, liver or kidney disease
• Current or past use of recreational or illicit drugs, or a history of drug abuse or dependence, or increased alcohol consumption

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

Hartley P, Shentu Y, Betz-Schiff P, Golm GT, Sisk CM, Engel SS, Shankar RR. Efficacy and Tolerability of Sitagliptin Compared with Glimepiride in Elderly Patients with Type 2 Diabetes Mellitus and Inadequate Glycemic Control: A Randomized, Double-Blind, Non-Inferiority Trial. Drugs Aging. 2015 Jun;32(6):469-76. doi: 10.1007/s40266-015-0271-z.

Reference Type: RESULT

PMID: 26041585 (View on PubMed)

Other Identifiers

0431-251

Identifier Type: -

Identifier Source: org_study_id