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

May 4, 2017 updated by: Merck Sharp & Dohme LLC

A Phase III, Multicenter, Double-Blind, Randomized, Active-Controlled Study to Evaluate the Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control

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.

Study Overview

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).

Study Type

Interventional

Enrollment (Actual)

480

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

65 years to 85 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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
Sitagliptin phosphate 100 mg or 50 mg once daily (QD)
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.
Other Names:
  • Januvia
Matching placebo tablets to glimepiride to allow for blinding.
Active Comparator: Glimepiride
Glimepiride 1-6 mg QD
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.
Other Names:
  • Amaryl
Matching placebo tablets to sitagliptin to allow for blinding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30
Time Frame: Baseline and 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
Time Frame: 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)
Time Frame: Up to Week 30

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
Time Frame: Up to Week 30

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
Time Frame: Baseline and Week 30
Plasma samples were collected from participants after an overnight fast at baseline and Week 30 to determine the mean change from baseline in participant FPG.
Baseline and Week 30
Percentage of Participants With HbA1c <7.0% at Week 30
Time Frame: Week 30
Participant whole blood samples were collected at Week 30 to determine the number of participants achieving HbA1c <7.0% at Week 30. 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.
Week 30
Percentage of Participants With HbA1c <6.5% at Week 30
Time Frame: Week 30
Participant whole blood samples were collected at Week 30 to determine the number of participants achieving HbA1c <6.5% at Week 30. Hemoglobin A1c 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.
Week 30
LS Mean Change From Baseline in Participant Body Weight at Week 30
Time Frame: Baseline and Week 30
Participants were only permitted to wear a drape gown and undergarments (no street clothes, no shoes or socks) for this evaluation. Body weight was measured after voiding (to the nearest 0.1 kg) and measurements were collected until 2 consecutive measurements did not differ by more than 0.2 kg from each other. Body weight measurements were evaluated using a standardized, calibrated digital scale and was reported in kilograms (kg) at baseline and Week 30.
Baseline and Week 30

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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)

August 16, 2010

Primary Completion (Actual)

October 31, 2012

Study Completion (Actual)

October 31, 2012

Study Registration Dates

First Submitted

August 25, 2010

First Submitted That Met QC Criteria

August 25, 2010

First Posted (Estimate)

August 27, 2010

Study Record Updates

Last Update Posted (Actual)

June 5, 2017

Last Update Submitted That Met QC Criteria

May 4, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

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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