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

NCT00943852 | Completed Phase 1 Results

• 3 other identifiers: 0954-317MK0954-3172009_610
• Study Type: interventional
• Target: 13
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Hypertension

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (5)

1

ACTIVE COMPARATOR

losartan 100 mg

Drug: losartan potassium

2

ACTIVE COMPARATOR

ISMN 60 mg

Drug: Comparator: isosorbide mononitrate (ISMN)

3

ACTIVE COMPARATOR

losartan 100 mg + ISMN 15 mg

Drug: Comparator: losartan + ISMN

4

ACTIVE COMPARATOR

losartan 100 mg + ISMN 60 mg

Drug: Comparator: losartan + ISMN

5

PLACEBO COMPARATOR

Placebo

Drug: Comparator: Placebo

Interventions

losartan potassium DRUG

Single dose losartan 100 mg in one of five treatment periods

Also known as: COZAAR

1

Comparator: isosorbide mononitrate (ISMN) DRUG

Single dose ISMN 60 mg in one of five treatment periods

Also known as: IMDUR

2

Comparator: losartan + ISMN DRUG

Single dose losartan 100 mg and ISMN 15 mg in one of five treatment periods

3

Comparator: Placebo DRUG

Single dose placebo only in one of five treatment periods

5

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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®

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Kaufman R, Nunes I, Bolognese JA, Miller DL, Salotti D, McCarthy JM, Smith WB, Herman GA, Feig PU. Single-dose effects of isosorbide mononitrate alone or in combination with losartan on central blood pressure. J Am Soc Hypertens. 2010 Nov-Dec;4(6):311-8. doi: 10.1016/j.jash.2010.10.004.

  PMID: 21130977 RESULT

MeSH Terms

Conditions

Hypertension

Interventions

Losartan; isosorbide-5-mononitrate

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Limitations and Caveats

Due to lower than expected Blood Pressure's in individual patients, an interim analysis was undertaken after 11 patients had completed 3 to 5 of the study periods; enough data was already collected to meet objectives, so the trial was stopped early.

Results Point of Contact

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

1-800-672-6372

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: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2009
• First Posted: July 22, 2009
• Study Start: August 1, 2006
• Primary Completion: December 1, 2006
• Study Completion: December 1, 2006
• Last Updated: February 9, 2022
• Results First Posted: July 15, 2010

Record last verified: 2022-02