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

NCT01189890 | Completed Phase 3 Results

• 1 other identifier: 0431-251
• Study Type: interventional
• Target: 480
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 Diabetes Mellitus, Hemoglobin A1C, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 inhibitor (DPP-4)

Outcome Measures

Primary Outcomes (4)

• Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30

  Participant whole blood samples were collected at baseline and Week 30 to determine the LS mean HbA1c change from baseline. HbA1c is a measure of the percentage of glycated hemoglobin in the blood and provides an indication of participant blood glucose control in the 2 to 3 months prior to the evaluation.

  Baseline and Week 30

• Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30

  Symptomatic hypoglycemia was defined as an episode with clinical symptoms attributed to hypoglycemia, without regard to glucose level. Participants were instructed to complete the Hypoglycemia Assessment Log (HAL) for any symptomatic episodes he or she believed represent hypoglycemia. If a fingerstick glucose was obtained before or shortly (i.e., within a few minutes) after treating, the value was recorded in the HAL. In addition, participants were instructed to record in the HAL any fingerstick glucose values ≤70 mg/dL (≤3.9 mmol/L) regardless of the presence of clinical symptoms.

  Up to Week 30

• Number of Participants Experiencing An Adverse Event (AE)

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the treatment administered.

  Up to Week 30

• Number of Participants Discontinuing Study Treatment Due to An AE

  An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of the treatment administered.

  Up to Week 30

Secondary Outcomes (4)

• LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30

  Baseline and Week 30

• Percentage of Participants With HbA1c <7.0% at Week 30

  Week 30

• Percentage of Participants With HbA1c <6.5% at Week 30

  Week 30

• LS Mean Change From Baseline in Participant Body Weight at Week 30

  Baseline and Week 30

Study Arms (2)

Sitagliptin

EXPERIMENTAL

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

Drug: sitagliptin phosphate; Drug: Placebo to Glimepiride

Glimepiride

ACTIVE COMPARATOR

Glimepiride 1-6 mg QD

Drug: Glimepiride; Drug: Placebo to Sitagliptin

Interventions

sitagliptin phosphate 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.

Also known as: Januvia

Sitagliptin

Glimepiride 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.

Also known as: Amaryl

Glimepiride

Placebo to Sitagliptin DRUG

Matching placebo tablets to sitagliptin to allow for blinding.

Glimepiride

Placebo to Glimepiride DRUG

Matching placebo tablets to glimepiride to allow for blinding.

Sitagliptin

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Diagnosis of type 2 diabetes mellitus

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 26041585 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate; 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

Results Point of Contact

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

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

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 25, 2010
• First Posted: August 27, 2010
• Study Start: August 16, 2010
• Primary Completion: October 31, 2012
• Study Completion: October 31, 2012
• Last Updated: June 5, 2017
• Results First Posted: June 27, 2013

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share