Hypertension
Conditions
Brief summary
This study will qualify a functional model that can measure central blood pressure and vascular compliance effects through noninvasive means.
Interventions
DRUGlosartan potassium
Single dose losartan 100 mg in one of five treatment periods
DRUGComparator: isosorbide mononitrate (ISMN)
Single dose ISMN 60 mg in one of five treatment periods
DRUGComparator: losartan + ISMN
Single dose losartan 100 mg and ISMN 15 mg in one of five treatment periods
DRUGComparator: Placebo
Single dose placebo only in one of five treatment periods
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 70 Years
Healthy volunteers
No
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®
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline and 10 hours postdose | 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. |
| Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo | Baseline and 10 hours postdose | 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. |
Participant flow
Recruitment details
First Patient Entered: 31-Aug-2006 Last Patient Last Visit: 11-Dec-2006 Number of Sites: 1
Participants by arm
| Arm | Count |
|---|---|
| All Participants in Study | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Washout Period After Period 1 Treatment | BP too low for dosing at the next period | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Washout Period After Period 2 Treatment | Trial stopped early | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Washout Period After Period 3 Treatment | Did not meet criteria for next period | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Washout Period After Period 4 Treatment | Not taking medication per protocol | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout Period After Period 4 Treatment | Trial stopped early | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants in Study |
|---|---|
| Age, Continuous | 57.2 years |
| Diastolic Blood Pressure | 90.6 mm Hg |
| Exclusionary Medication Washout No | 10 participants |
| Exclusionary Medication Washout Yes | 3 participants |
| Heart Rate | 75.4 Beats per Minute |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 6 Participants |
| Systolic Blood Pressure | 141.5 mm Hg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 2 / 11 | 1 / 13 | 4 / 11 | 4 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 | 0 / 13 | 0 / 11 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline and 10 hours postdose
Population: All subjects who received single doses of Losartan 100 mg + ISMN 60 mg and/or single dose of placebo
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan 100 mg + ISMN 60 mg | Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo | -24.9 Percent Change | Standard Deviation 3.8 |
| Losartan 100 mg | Mean Augmentation Index Percent Change From Baseline After Single Doses of Losartan 100 mg + ISMN 60 mg Versus Single Dose of Placebo | -1.3 Percent Change | Standard Deviation 3.8 |
p-value: <0.001ANOVA
Primary
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.
Time frame: Baseline and 10 hours postdose
Population: All subjects who received single doses of losartan 100 mg + ISMN 60 mg and/or single dose of losartan 100 mg
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Losartan 100 mg + ISMN 60 mg | 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 | -24.9 Percent Change | Standard Deviation 3.8 |
| Losartan 100 mg | 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 | -1.8 Percent Change | Standard Deviation 3.8 |
p-value: <0.001ANOVA