Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
sitagliptin phosphate
Glimepiride
Placebo to Sitagliptin
Placebo to Glimepiride
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Type 2 Diabetes Mellitus, Hemoglobin A1C, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), dipeptidyl peptidase 4 inhibitor (DPP-4)
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Sitagliptin
Glimepiride
Arm Description
Sitagliptin phosphate 100 mg or 50 mg once daily (QD)
Glimepiride 1-6 mg QD
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at 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.
Percentage of Participants With HbA1c <7.0% at 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.
Percentage of Participants With HbA1c <6.5% at 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.
LS Mean Change From Baseline in Participant Body Weight at 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01189890
Brief Title
Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251)
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
August 16, 2010 (Actual)
Primary Completion Date
October 31, 2012 (Actual)
Study Completion Date
October 31, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
480 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sitagliptin
Arm Type
Experimental
Arm Description
Sitagliptin phosphate 100 mg or 50 mg once daily (QD)
Arm Title
Glimepiride
Arm Type
Active Comparator
Arm Description
Glimepiride 1-6 mg QD
Intervention Type
Drug
Intervention Name(s)
sitagliptin phosphate
Other Intervention Name(s)
Januvia
Intervention Description
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
Intervention Name(s)
Glimepiride
Other Intervention Name(s)
Amaryl
Intervention Description
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
Intervention Name(s)
Placebo to Sitagliptin
Intervention Description
Matching placebo tablets to sitagliptin to allow for blinding.
Intervention Type
Drug
Intervention Name(s)
Placebo to Glimepiride
Intervention Description
Matching placebo tablets to glimepiride to allow for blinding.
Primary Outcome Measure Information:
Title
Least Squares (LS) Mean Change From Baseline in Hemoglobin A1c (HbA1c) at Week 30
Description
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.
Time Frame
Baseline and Week 30
Title
Number of Participants With an Adverse Event of Symptomatic Hypoglycemia Up to Week 30
Description
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.
Time Frame
Up to Week 30
Title
Number of Participants Experiencing An Adverse Event (AE)
Description
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.
Time Frame
Up to Week 30
Title
Number of Participants Discontinuing Study Treatment Due to An AE
Description
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.
Time Frame
Up to Week 30
Secondary Outcome Measure Information:
Title
LS Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
Description
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.
Time Frame
Baseline and Week 30
Title
Percentage of Participants With HbA1c <7.0% at Week 30
Description
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.
Time Frame
Week 30
Title
Percentage of Participants With HbA1c <6.5% at Week 30
Description
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.
Time Frame
Week 30
Title
LS Mean Change From Baseline in Participant Body Weight at Week 30
Description
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.
Time Frame
Baseline and Week 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
26041585
Citation
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.
Results Reference
result
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Safety and Efficacy of Sitagliptin Compared With Glimepiride in Elderly Participants With Type 2 Diabetes Mellitus (MK-0431-251)
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