The Effect of Losartan and Losartan Plus Isosorbide Mononitrate on Central Blood Pressure Measurements (0954-317)

Study Overview
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Brief Summary
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This study will qualify a functional model that can measure central blood pressure and vascular compliance effects through noninvasive means.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, 5-Period Crossover Study to Evaluate the Effects of a Single Dose of Losartan, a Single Dose of Isosorbide Mononitrate (ISMN), and Single Doses of Losartan + ISMN on Central Blood Pressure Measurements in Mildly Hypertensive Patients

Conditions
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Hypertension

Intervention / Treatment
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* Drug: losartan potassium
* Drug: Comparator: isosorbide mononitrate (ISMN)
* Drug: Comparator: losartan + ISMN
* Drug: Comparator: losartan + ISMN
* Drug: Comparator: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is in good health with the exception of mild to moderate hypertension Patient is willing to comply with the study restrictions Patient does not smoke Exclusion Criteria: Patient has a history of any illness that might confound the results of the study or make participation in the study unsafe Patient is taking a prescription medication that is contraindicated for use with COZAAR® or IMDUR® Patient has a condition for which there is a warning, contraindication, or precaution against the use of COZAAR® or IMDUR®

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>losartan 100 mg | Drug: losartan potassium<br>* Single dose losartan 100 mg in one of five treatment periods<br>* Other names: COZAAR;|
| Active Comparator: 2<br>ISMN 60 mg | Drug: Comparator: isosorbide mononitrate (ISMN)<br>* Single dose ISMN 60 mg in one of five treatment periods<br>* Other names: IMDUR;|
| Active Comparator: 3<br>losartan 100 mg + ISMN 15 mg | Drug: Comparator: losartan + ISMN<br>* Single dose losartan 100 mg and ISMN 15 mg in one of five treatment periods<br>|
| Active Comparator: 4<br>losartan 100 mg + ISMN 60 mg | Drug: Comparator: losartan + ISMN<br>* Single dose losartan 100 mg and ISMN 60 mg in one of five treatment periods<br>|
| Placebo Comparator: 5<br>Placebo | Drug: Comparator: Placebo<br>* Single dose placebo only in one of five treatment periods<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg Plus ISMN 60 mg Versus Single Dose of Losartan 100 mg | The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline. | Baseline and 10 hours postdose | 
| Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo | The augmentation index (AIx) is defined as the ratio of augmentation (Δ P) to central pulse pressure and expressed as percent. AIx = (ΔP/PP) x 100, where P = pressure and PP = Pulse Pressure. A mathematical transfer function translated the peripheral wave form into a central waveform using an FDA approved process based on directly recorded arterial pressure values. The mean AIx for each subject was estimated as a time-weighted average over the 10-hour post dose observation period and expressed as a change from baseline. | Baseline and 10 hours postdose |