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

NCT00871871 | Completed Phase 1 Results

• 2 other identifiers: 0000-1172009_567
• Study Type: interventional
• Target: 64
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Hypertension

Outcome Measures

Primary Outcomes (4)

• Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Glucose Tolerance (IGT)

  Steady state was defined as 90-120 minutes post-dose. IGT was defined as a 2 hour plasma glucose \>= 140 and \<= 199 mg/dL during a 75g oral glucose tolerance test at screening.

  90 -120 minutes post-dose

• Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants With Impaired Fasting Glucose (IFG)

  Steady state was defined as 90-120 minutes post-dose. IFG was defined as fasting plasma glucose (FPG) between 100 and 125 mg/dL at screening.

  90 -120 minutes post-dose

• Part I: Change in Insulin Secretion at Steady-state Compared to Placebo in Participants Who Had Normal Glucose Tolerance (NGT)

  Steady state was defined as 90-120 minutes post-dose. NGT participants (FPG \<100 mg/dL \& 2 hour plasma glucose (PG) \<140 mg/dL during a 75g oral glucose tolerance test (OGTT) at screening) were neither Impaired Glucose Tolerant (IGT) nor Impaired Fasting Glucose (IFG). IGT was defined as a 2 hour plasma glucose \>= 140 and \<= 199 mg/dL during a 75g oral glucose tolerance test at screening. IFG was defined as FPG between 100 and 125 mg/dL at screening.

  90 -120 minutes post-dose

• Part II: Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady-state

  Steady state was defined as 90-120 minutes post-dose. The ratio was the quantity of glucose disposed by the body per kg body weight per minute at steady state divided by the approximate steady state plasma insulin concentration. The approximate steady state plasma insulin concentration was estimated by the time-weighted average of the insulin concentration measured at 10 minute intervals in which time = 90, 100, 110, and 120 minutes.

  90 -120 minutes post-dose

Secondary Outcomes (3)

• Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Glucose Tolerant (IGT)

  90 -120 minutes post-dose

• Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Impaired Fasting Glucose (IFG)

  90 -120 minutes post-dose

• Part I: Change in the Ratio of Whole Body Glucose Disposal to Plasma Insulin at Steady State in Participants With Normal Glucose Tolerant (NGT)

  90 -120 minutes post-dose

Study Arms (4)

Part I, Placebo-HCTZ

EXPERIMENTAL

Placebo in Period 1 followed by HCTZ in Period 2

Drug: Hydrochlorothiazide (HCTZ); Drug: Comparator: Placebo to HCTZ

Part I, HCTZ-Placebo

EXPERIMENTAL

HCTZ in Period 1, followed by placebo in Period 2

Drug: Hydrochlorothiazide (HCTZ); Drug: Comparator: Placebo to HCTZ

Part II, Placebo-ISMN

EXPERIMENTAL

Placebo in Period 1, followed by ISMN in Period 2

Drug: Isosorbide mononitrate (ISMN); Drug: Comparator: Placebo to ISMN

Part II, ISMN-Placebo

EXPERIMENTAL

ISMN in Period 1, followed by placebo in Period 2

Drug: Isosorbide mononitrate (ISMN); Drug: Comparator: Placebo to ISMN

Interventions

Hydrochlorothiazide (HCTZ) DRUG

HCTZ 50 mg (two 25 mg capsules) once daily for 4 weeks per treatment period.

Also known as: HCTZ

Part I, HCTZ-Placebo; Part I, Placebo-HCTZ

Comparator: Placebo to HCTZ DRUG

Placebo to HCTZ two 0 mg capsules once daily for 4 weeks per treatment period

Part I, HCTZ-Placebo; Part I, Placebo-HCTZ

Isosorbide mononitrate (ISMN) DRUG

ISMN 60 mg extended release capsule once daily for 4 weeks per treatment period

Part II, ISMN-Placebo; Part II, Placebo-ISMN

Comparator: Placebo to ISMN DRUG

Placebo to ISMN 0 mg capsule once daily for 4 weeks per treatment period

Part II, ISMN-Placebo; Part II, Placebo-ISMN

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypertension

Interventions

Hydrochlorothiazide; isosorbide-5-mononitrate

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2009
• First Posted: March 30, 2009
• Study Start: March 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: July 28, 2015
• Results First Posted: September 22, 2011

Record last verified: 2015-07