Effects of Glimepiride on Recovery From Hypoglycemia in Participants With Type 2 Diabetes Mellitus (MK-0000-253)

NCT ID: NCT01614769

Last Updated: 2018-08-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-18
• Study Completion Date: 2013-01-23

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo → Glimepiride 2 mg → Glimepiride 4 mg

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 2 mg

Intervention Type: DRUG

One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 4 mg

Intervention Type: DRUG

Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.

Hypoglycemic Clamp

Intervention Type: PROCEDURE

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.

Glimepiride 2 mg → Glimepiride 4 mg → Placebo

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 2 mg

Intervention Type: DRUG

One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 4 mg

Intervention Type: DRUG

Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.

Hypoglycemic Clamp

Intervention Type: PROCEDURE

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.

Glimepiride 4 mg → Placebo → Glimepiride 2 mg

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 2 mg

Intervention Type: DRUG

One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 4 mg

Intervention Type: DRUG

Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.

Hypoglycemic Clamp

Intervention Type: PROCEDURE

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.

Placebo → Glimepiride 4 mg → Glimepiride 2 mg

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 2 mg

Intervention Type: DRUG

One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 4 mg

Intervention Type: DRUG

Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.

Hypoglycemic Clamp

Intervention Type: PROCEDURE

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.

Glimepiride 2 mg → Placebo → Glimepiride 4 mg

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 2 mg

Intervention Type: DRUG

One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 4 mg

Intervention Type: DRUG

Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.

Hypoglycemic Clamp

Intervention Type: PROCEDURE

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.

Glimepiride 4 mg → Glimepiride 2 mg → Placebo

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.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 2 mg

Intervention Type: DRUG

One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.

Glimepiride 4 mg

Intervention Type: DRUG

Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.

Hypoglycemic Clamp

Intervention Type: PROCEDURE

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.

Interventions

Placebo

Two gross-matched glimepiride placebo tablets taken on Day -1 and Day 1 of the three treatment periods.

Intervention Type: DRUG

Glimepiride 2 mg

One placebo tablet and one 2-mg glimepiride tablet taken on Day -1 and Day 1 of the three treatment periods.

Intervention Type: DRUG

Glimepiride 4 mg

Two 2-mg glimepiride tablets taken on Day -1 and Day 1 of the three treatment periods.

Intervention Type: DRUG

Hypoglycemic Clamp

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.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Study Documents

Document Type: CSR Snyposis Link

View Document

Other Identifiers

0000-253

Identifier Type: -

Identifier Source: org_study_id