Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251 AM2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01189890
First received: August 25, 2010
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: sitagliptin phosphate
Drug: Glimepiride
Drug: Placebo to Sitagliptin
Drug: Placebo to Glimepiride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30 [ Time Frame: Baseline and Week 30 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30 [ Time Frame: Up to Week 30 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to Week 30 ] [ Designated as safety issue: Yes ]

    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.


  • Number of Participants Discontinuing Study Treatment Due to An AE [ Time Frame: Up to Week 30 ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30 [ Time Frame: Baseline and Week 30 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HbA1c <7.0% at Week 30 [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With HbA1c <6.5% at Week 30 [ Time Frame: Week 30 ] [ Designated as safety issue: No ]
    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.

  • LS Mean Change From Baseline in Participant Body Weight at Week 30 [ Time Frame: Baseline and Week 30 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 480
Study Start Date: August 2010
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
Sitagliptin phosphate 100 mg or 50 mg once daily (QD)
Drug: 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.
Other Name: Januvia
Drug: Placebo to Glimepiride
Matching placebo tablets to glimepiride to allow for blinding.
Active Comparator: Glimepiride
Glimepiride 1-6 mg QD
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.
Other Name: Amaryl
Drug: Placebo to Sitagliptin
Matching placebo tablets to sitagliptin to allow for blinding.

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).

  Eligibility

Ages Eligible for Study:   65 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01189890     History of Changes
Other Study ID Numbers: 0431-251
Study First Received: August 25, 2010
Results First Received: May 8, 2013
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Type 2 Diabetes Mellitus, Hemoglobin A1C, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 inhibitor (DPP-4)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Gastric Inhibitory Polypeptide
Sitagliptin
Glimepiride
Dipeptidyl-Peptidase IV Inhibitors
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Hypoglycemic Agents
Immunosuppressive Agents
Immunologic Factors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014