Back to resultsEffects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253)
Primary Purpose
Type 2 Diabetes Mellitus
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Placebo
Glimepiride 2 mg
Glimepiride 4 mg
Hypoglycemic Clamp
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Has clinically confirmed diagnosis of type 2 diabetes mellitus (T2DM) controlled by diet and exercise alone, or treated by metformin only with same dose for >= 12 weeks prior to screening visit.
- Females of reproductive potential who demonstrate nongravid state, agree to use (and/or have partner use) two acceptable methods of birth control starting at least two weeks prior to study, throughout study, and at least two weeks after last dose of study drug.
- Females of non-reproductive potential, post menopausal, status post hysterectomy, oophorectomy or tubal ligation.
- Is in good health, other than T2DM.
- Has been a nonsmoker and/or non user of nicotine-containing products for the previous 6 months. If discontinued use for previous 3 months, may be enrolled at investigator's discretion.
- Will follow American Heart Association weight maintaining diet and exercise program or equivalent beginning 2 weeks prior to study until poststudy visit.
- At screening visit has a Body Mass Index (BMI) =< 40 kg/m^2.
- At screening visit has a Hemoglobin A1c (HbA1c) of >= 7% and < 10% (+/- 0.1%).
- On the morning of randomization at predose has fasting plasma glucose (FPG) >= 126 mg/dL, and =< 250 mg/dL.
Exclusion Criteria:
- Has a history of stroke, chronic seizures, or major neurological disorder.
- Has a history of any illness that might confound the results of the study or pose additional risk to the participant.
- Has a history of type 1 diabetes mellitus, ketoacidosis, C-peptide =< 0.8 ng/mL, secondary forms of diabetes or diabetic complications.
- Has a history of neoplastic disease.
- Is a nursing mother.
- Has been treated =< one year of screening visit with sulfonylurea agents, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogs, or insulin.
- Has received treatment within =< 12 weeks of screening visit with a peroxisome proliferator-activated receptor γ (PPARγ) agonist.
- Is taking medications for a co-morbid condition or anticipates taking new medications beginning 2 weeks prior to study.
- Consumes excessive amounts of alcohol or caffeinated beverages.
- Is a regular user of illicit drugs, or has a history of drug abuse within the previous 6 months.
- Has had major surgery, lost 500 mL of blood, or participated in another investigational study within 4 weeks prior to screening visit.
- Is on a weight loss program, but not in the maintenance phase, or treated with a weight loss medication within 8 weeks of prestudy visit.
- Has a history of severe allergies, anaphylactic reaction or intolerability to drugs, food, insulin, glimepiride or sulfonamide derivatives.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Placebo → Glimepiride 2 mg → Glimepiride 4 mg
Glimepiride 2 mg → Glimepiride 4 mg → Placebo
Glimepiride 4 mg → Placebo → Glimepiride 2 mg
Placebo → Glimepiride 4 mg → Glimepiride 2 mg
Glimepiride 2 mg → Placebo → Glimepiride 4 mg
Glimepiride 4 mg → Glimepiride 2 mg → Placebo
Arm Description
Participants received placebo in the first period, 2 mg glimepiride in the second period and 4 mg glimepiride in the third period, with a 7-day washout between each period.
Participants received 2 mg glimepiride in the first period, 4 mg glimepiride in the second period and placebo in the third period, with a 7-day washout between each period.
Participants received 4 mg glimepiride in the first period, placebo in the second period and 2 mg glimepiride in the third period, with a 7-day washout between each period.
Participants received placebo in the first period, 4 mg glimepiride in the second period and 2 mg glimepiride in the third period, with a 7-day washout between each period.
Participants received 2 mg glimepiride in the first period, placebo in the second period and 4 mg glimepiride in the third period, with a 7-day washout between each period.
Participants received 4 mg glimepiride in the first period, 2 mg glimepiride in the second period and placebo in the third period, with a 7-day washout between each period.
Outcomes
Primary Outcome Measures
Recovery Time From Hypoglycemia to Euglycemia
Immediately after release of the hypoglycemic clamp, which maintained blood glucose close to 50 mg/dL, the time taken until glucose reached euglycemia, defined as 3 consecutive measurements >= 70 mg/dL, is called the recovery time.
Rate of Recovery From Hypoglycemia to Euglycemia
The rate of recovery is the difference in concentration between blood glucose at euglycemia and at the end of the hypoglycemic clamp, divided by the recovery time.
Incremental Weighted Average Blood Glucose Concentration Over 3 Hours of Hypoglycemic Recovery
The incremental weighted average qualitatively assesses overall hypoglycemic recovery by measuring mean glycemia over the 3 hour recovery period. Blood glucose measured at the release of the hypoglycemic clamp, considered the baseline value, was subtracted from blood glucose values measured over the ensuing 3 hours of hypoglycemic recovery. These differences from baseline were averaged to calculate the incremental weighted average blood glucose concentration.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01614769
Brief Title
Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253)
Official Title
A Study to Assess the Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
July 18, 2012 (Actual)
Primary Completion Date
January 9, 2013 (Actual)
Study Completion Date
January 23, 2013 (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
This study aims to assess how glimepiride affects the recovery from hypoglycemia in participants with type 2 diabetes mellitus. The primary objective is to estimate the time taken by participants to recover from hypoglycemia to euglycemia after treatment with either 2 mg or 4 mg of glimepiride when compared to placebo.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo → Glimepiride 2 mg → Glimepiride 4 mg
Arm Type
Experimental
Arm Description
Participants received placebo in the first period, 2 mg glimepiride in the second period and 4 mg glimepiride in the third period, with a 7-day washout between each period.
Arm Title
Glimepiride 2 mg → Glimepiride 4 mg → Placebo
Arm Type
Experimental
Arm Description
Participants received 2 mg glimepiride in the first period, 4 mg glimepiride in the second period and placebo in the third period, with a 7-day washout between each period.
Arm Title
Glimepiride 4 mg → Placebo → Glimepiride 2 mg
Arm Type
Experimental
Arm Description
Participants received 4 mg glimepiride in the first period, placebo in the second period and 2 mg glimepiride in the third period, with a 7-day washout between each period.
Arm Title
Placebo → Glimepiride 4 mg → Glimepiride 2 mg
Arm Type
Experimental
Arm Description
Participants received placebo in the first period, 4 mg glimepiride in the second period and 2 mg glimepiride in the third period, with a 7-day washout between each period.
Arm Title
Glimepiride 2 mg → Placebo → Glimepiride 4 mg
Arm Type
Experimental
Arm Description
Participants received 2 mg glimepiride in the first period, placebo in the second period and 4 mg glimepiride in the third period, with a 7-day washout between each period.
Arm Title
Glimepiride 4 mg → Glimepiride 2 mg → Placebo
Arm Type
Experimental
Arm Description
Participants received 4 mg glimepiride in the first period, 2 mg glimepiride in the second period and placebo in the third period, with a 7-day washout between each period.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.
Intervention Type
Drug
Intervention Name(s)
Glimepiride 2 mg
Intervention Description
One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.
Intervention Type
Drug
Intervention Name(s)
Glimepiride 4 mg
Intervention Description
Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.
Intervention Type
Procedure
Intervention Name(s)
Hypoglycemic Clamp
Intervention Description
On Day 1 of the three treatment periods, 180 minutes after drug treatment, a fixed-rate insulin infusion is combined with a variable-rate dextrose infusion to maintain plasma glucose concentrations at close to 50 mg/dL for 30 minutes.
Primary Outcome Measure Information:
Title
Recovery Time From Hypoglycemia to Euglycemia
Description
Immediately after release of the hypoglycemic clamp, which maintained blood glucose close to 50 mg/dL, the time taken until glucose reached euglycemia, defined as 3 consecutive measurements >= 70 mg/dL, is called the recovery time.
Time Frame
From 1 to 180 minutes post hypoglycemic clamp
Title
Rate of Recovery From Hypoglycemia to Euglycemia
Description
The rate of recovery is the difference in concentration between blood glucose at euglycemia and at the end of the hypoglycemic clamp, divided by the recovery time.
Time Frame
From 1 to 180 minutes post hypoglycemic clamp
Title
Incremental Weighted Average Blood Glucose Concentration Over 3 Hours of Hypoglycemic Recovery
Description
The incremental weighted average qualitatively assesses overall hypoglycemic recovery by measuring mean glycemia over the 3 hour recovery period. Blood glucose measured at the release of the hypoglycemic clamp, considered the baseline value, was subtracted from blood glucose values measured over the ensuing 3 hours of hypoglycemic recovery. These differences from baseline were averaged to calculate the incremental weighted average blood glucose concentration.
Time Frame
From 1 to 180 minutes post hypoglycemic clamp
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has clinically confirmed diagnosis of type 2 diabetes mellitus (T2DM) controlled by diet and exercise alone, or treated by metformin only with same dose for >= 12 weeks prior to screening visit.
Females of reproductive potential who demonstrate nongravid state, agree to use (and/or have partner use) two acceptable methods of birth control starting at least two weeks prior to study, throughout study, and at least two weeks after last dose of study drug.
Females of non-reproductive potential, post menopausal, status post hysterectomy, oophorectomy or tubal ligation.
Is in good health, other than T2DM.
Has been a nonsmoker and/or non user of nicotine-containing products for the previous 6 months. If discontinued use for previous 3 months, may be enrolled at investigator's discretion.
Will follow American Heart Association weight maintaining diet and exercise program or equivalent beginning 2 weeks prior to study until poststudy visit.
At screening visit has a Body Mass Index (BMI) =< 40 kg/m^2.
At screening visit has a Hemoglobin A1c (HbA1c) of >= 7% and < 10% (+/- 0.1%).
On the morning of randomization at predose has fasting plasma glucose (FPG) >= 126 mg/dL, and =< 250 mg/dL.
Exclusion Criteria:
Has a history of stroke, chronic seizures, or major neurological disorder.
Has a history of any illness that might confound the results of the study or pose additional risk to the participant.
Has a history of type 1 diabetes mellitus, ketoacidosis, C-peptide =< 0.8 ng/mL, secondary forms of diabetes or diabetic complications.
Has a history of neoplastic disease.
Is a nursing mother.
Has been treated =< one year of screening visit with sulfonylurea agents, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogs, or insulin.
Has received treatment within =< 12 weeks of screening visit with a peroxisome proliferator-activated receptor γ (PPARγ) agonist.
Is taking medications for a co-morbid condition or anticipates taking new medications beginning 2 weeks prior to study.
Consumes excessive amounts of alcohol or caffeinated beverages.
Is a regular user of illicit drugs, or has a history of drug abuse within the previous 6 months.
Has had major surgery, lost 500 mL of blood, or participated in another investigational study within 4 weeks prior to screening visit.
Is on a weight loss program, but not in the maintenance phase, or treated with a weight loss medication within 8 weeks of prestudy visit.
Has a history of severe allergies, anaphylactic reaction or intolerability to drugs, food, insulin, glimepiride or sulfonamide derivatives.
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Snyposis Link
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=0000-253&kw=0000-253&tab=access
Learn more about this trial
Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253)
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