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| ID | Type | Description | Link |
|---|---|---|---|
| MK0954-317 | |||
| 2009_610 |
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This study will qualify a functional model that can measure central blood pressure and vascular compliance effects through noninvasive means.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | losartan 100 mg |
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| 2 | Active Comparator | ISMN 60 mg |
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| 3 | Active Comparator | losartan 100 mg + ISMN 15 mg |
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| 4 | Active Comparator | losartan 100 mg + ISMN 60 mg |
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| 5 | Placebo Comparator | Placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| losartan potassium | Drug | Single dose losartan 100 mg in one of five treatment periods |
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| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21130977 | Result | 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. |
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First Patient Entered: 31-Aug-2006
Last Patient Last Visit: 11-Dec-2006
Number of Sites: 1
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo / Losartan / Losartan + ISMN / Losartan + ISMN / ISMN | Placebo / Losartan 100 mg / Losartan 100 mg + Isosorbide Mononitrate (ISMN) 15 mg / Losartan 100 mg + ISMN 60 mg / ISMN 60 mg - single dose with ≥ 4 days washout between doses |
| FG001 | Losartan / ISMN / Losartan + ISMN / Placebo / Losartan + ISMN |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Period of Treatment Intervention |
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| Comparator: isosorbide mononitrate (ISMN) | Drug | Single dose ISMN 60 mg in one of five treatment periods |
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| Comparator: losartan + ISMN | Drug | Single dose losartan 100 mg and ISMN 15 mg in one of five treatment periods |
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| Comparator: losartan + ISMN | Drug | Single dose losartan 100 mg and ISMN 60 mg in one of five treatment periods |
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| Comparator: Placebo | Drug | Single dose placebo only in one of five treatment periods |
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Losartan 100 mg / ISMN 60 mg / Losartan 100 mg + ISMN 60 mg / Placebo / Losartan 100 mg + ISMN 15 mg - single dose with ≥ 4 days washout between doses |
| FG002 | ISMN / Losartan + ISMN / Placebo / Losartan / Losartan + ISMN | ISMN 60 mg / Losartan 100 mg + ISMN 15 mg / Placebo / Losartan 100 mg / Losartan 100 mg + ISMN 60 mg - single dose with ≥ 4 days washout between doses |
| FG003 | Losartan + ISMN / Losartan + ISMN / Losartan / ISMN / Placebo | Losartan 100 mg + ISMN 15 mg / Losartan 100 mg + ISMN 60 mg / Losartan 100 mg / ISMN 60 mg / Placebo - single dose with ≥ 4 days washout between doses |
| FG004 | Losartan + ISMN / Placebo / ISMN / Losartan + ISMN / Losartan | Losartan 100 mg + ISMN 60 mg / Placebo / ISMN 60 mg / Losartan 100 mg + ISMN 15 mg / Losartan 100 mg - single dose with ≥ 4 days washout between doses |
| FG005 | Placebo / ISMN / Losartan / Losartan + ISMN / Losartan + ISMN | Placebo / ISMN 60 mg / Losartan 100 mg / Losartan 100 mg + ISMN 60 mg / Losartan 100 mg + ISMN 15 mg - single dose with ≥ 4 days washout between doses |
| FG006 | Losartan / Losartan + ISMN / ISMN / Placebo / Losartan + ISMN | Losartan 100 mg / Losartan 100 mg + ISMN 15 mg / ISMN 60 mg / Placebo / Losartan 100 mg + ISMN 60 mg - single dose with ≥ 4 days washout between doses |
| FG007 | ISMN / Losartan + ISMN / Losartan + ISMN / Losartan / Placebo | ISMN 60 mg / Losartan 100 mg + ISMN 60 mg / Losartan 100 mg + ISMN 15 mg / Losartan 100 mg / Placebo - single dose with ≥ 4 days washout between doses |
| FG008 | Losartan + ISMN / Placebo / Losartan + ISMN / ISMN / Losartan | Losartan 100 mg + ISMN 15 mg / Placebo / Losartan 100 mg + ISMN 60 mg / ISMN 60 mg / Losartan 100 mg - single dose with ≥ 4 days washout between doses |
| FG009 | Losartan + ISMN / Losartan / Placebo / Losartan + ISMN / ISMN | Losartan 100 mg + ISMN 60 mg / Losartan 100 mg / Placebo / Losartan 100 mg + ISMN 15 mg / ISMN 60 mg - single dose with ≥ 4 days washout between doses |
| COMPLETED |
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| NOT COMPLETED |
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| Washout Period After Period 1 Treatment |
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| Second Period of Treatment Intervention |
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| Washout Period After Period 2 Treatment |
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| Third Period of Treatment Intervention |
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| Washout Period After Period 3 Treatment |
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| Fourth Period of Treatment Intervention |
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| Washout Period After Period 4 Treatment |
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| Fifth Period of Treatment Intervention |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants in Study |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Exclusionary Medication Washout | Number | participants |
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| Diastolic Blood Pressure | Mean | Full Range | mm Hg |
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| Heart Rate | Mean | Full Range | Beats per Minute |
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| Systolic Blood Pressure | Mean | Full Range | mm Hg |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | All subjects who received single doses of losartan 100 mg + ISMN 60 mg and/or single dose of losartan 100 mg | Posted | Least Squares Mean | Standard Deviation | Percent Change | Baseline and 10 hours postdose |
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| 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. | All subjects who received single doses of Losartan 100 mg + ISMN 60 mg and/or single dose of placebo | Posted | Least Squares Mean | Standard Deviation | Percent Change | Baseline and 10 hours postdose |
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Run-in period through 14 days post last dose of study drug (documented by telephone contact or in person)
One (1) of the 13 enrolled subjects completed one period of the study and (1) of the 13 enrolled subjects completed 2 periods of the study prior to termination of the study.
These subjects were included in the AE summary tables having been exposed to treatment, but were not included in the statistical analysis.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 0 | 12 | 1 | 12 | |||
| EG001 | Losartan 100 mg | 0 | 11 | 2 | 11 | |||
| EG002 | Losartan 100 mg + ISMN 15 mg | 0 | 13 | 1 | 13 | |||
| EG003 | Losartan 100 mg + ISMN 60 mg | 0 | 11 | 4 | 11 | |||
| EG004 | ISMN 60 mg | 0 | 12 | 4 | 12 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA (10.1) | Non-systematic Assessment |
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| Oedema Peripheral | General disorders | MedDRA (10.1) | Non-systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA (10.1) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (10.1) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (10.1) | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (10.1) | Non-systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA (10.1) | Non-systematic Assessment |
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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.
Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | 1-800-672-6372 |
| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D019808 | Losartan |
| C030397 | isosorbide-5-mononitrate |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |
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| Trial stopped early |
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