Multiple Dose Effects of Hydrochlorothiazide and Isosorbide Mononitrate on Glucose Homeostasis (MK-0000-117)(Completed)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Hypertension

Treatments: Drug: Hydrochlorothiazide (HCTZ); Drug: Comparator: Placebo to HCTZ; Drug: Isosorbide mononitrate (ISMN); Drug: Comparator: Placebo to ISMN

Study type: Interventional

Funder types: Industry

Identifiers

NCT00871871

0000-117

2009_567

Details and patient eligibility

About

This study will measure and compare changes in insulin production and sensitivity using the hyperglycemic clamp technique in obese patients with impaired glucose tolerance and hypertension treated with placebo, isosorbide mononitrate (ISMN) or hydrochlorothiazide (HCTZ).

Enrollment: 64 patients

Sex: All

Ages: 35 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female participants must be post-menopausal
• Body Mass Index (BMI) of at least 29 kg/m^2
• Weight has been stable over the past 3 months
• Has never been treated for hypertension or is diagnosed with hypertension taking up to 2 anti-hypertensive medications
• Willing to stop hypertension treatment for 14 days prior to randomization and throughout the study
• Does not have a history of diabetes
• In good health with the exception of hypertension
• No history of abnormal heart rhythms
• Part I only: willing to comply with high potassium/low sodium diet for the duration of the study
• Willing to avoid strenuous physical activity during the study
• Nonsmoker and/or has not used nicotine for at least 3 months and agrees to refrain from use of tobacco-containing products throughout the study
• Agrees to refrain from consuming alcohol and caffeine during in-patient periods and to limit consumption at all other times during the study
• Agrees not to consume grapefruit, grapefruit products, and citrus, apple, and pineapple juices 2 weeks prior to administration of the first dose of study drug

Exclusion criteria

• History of any illness that may make their participation in the study unsafe or confuse the study results
• Taking spironolactone or eplerenone
• Cannot refrain from using any prescription or non-prescription drugs during the study
• On a weight loss program and is not in the maintenance phase
• Started a weight loss drug within 8 weeks of the first study visit
• Consumes excessive amounts of alcohol or caffeine
• Has had major surgery, donated or lost 1 unit of blood within 4 weeks of the first study visit
• History of multiple and/or severe allergies to drugs or food
• Is dehydrated

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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64 participants in 4 patient groups

Part I, Placebo-HCTZ

Experimental group

Description:

Placebo in Period 1 followed by HCTZ in Period 2

Treatment:

Drug: Comparator: Placebo to HCTZ

Drug: Hydrochlorothiazide (HCTZ)

Part I, HCTZ-Placebo

Experimental group

Description:

HCTZ in Period 1, followed by placebo in Period 2

Treatment:

Drug: Comparator: Placebo to HCTZ

Drug: Hydrochlorothiazide (HCTZ)

Part II, Placebo-ISMN

Experimental group

Description:

Placebo in Period 1, followed by ISMN in Period 2

Treatment:

Drug: Comparator: Placebo to ISMN

Drug: Isosorbide mononitrate (ISMN)

Part II, ISMN-Placebo

Experimental group

Description:

ISMN in Period 1, followed by placebo in Period 2

Treatment:

Drug: Comparator: Placebo to ISMN

Drug: Isosorbide mononitrate (ISMN)