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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004639-55 | EudraCT Number | ||
| MK-8892-007 | Other Identifier | Merck Protocol Number |
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This study will assess multiple doses of MK-8892 administered to participants with pulmonary hypertension "out of proportion" (PHOOP) and heart failure with reduced left ventricular ejection fraction (rEF). It is hypothesized that generally safe and well tolerated multiple doses of MK-8892 will achieve a true reduction from baseline in pulmonary vascular resistance (PVR) greater than 12%.
Sixteen participants with PHOOP/rEF were to receive multiple doses of MK-8892 titrated to the highest tolerated dose for each participant (up to 4 mg daily), and to undergo evaluation for safety and systemic hemodynamics and cardiac function. Only 4 participants were enrolled and completed the study due to a strategic business decision by the sponsor to terminate the clinical conduct of all MK-8892 ongoing trials including this trial.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-8892 | Experimental | Starting dose of 1 mg daily (oral); the dose may be titrated up on the 8th, 15th, and 22nd day of treatment to 2 mg, 3 mg, or 4 mg, respectively, for the duration of the study (28 days) as tolerated. For participants who reach one or more of the down-dosing criteria, there is an opportunity to decrease the dose back to a previously well-tolerated dose level, or to ½ of the starting dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-8892 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Pulmonary Vascular Resistance (PVR) | Pulmonary vascular resistance (PVR) is the general pressure which the right ventricle must counteract to pump blood through the lungs. PVR was measured by right heart catheterization performed prior to dosing at baseline (Day 1) and 4 hours postdose on Day 28. Percentage change in PVR from baseline at Day 28 was calculated as [(Baseline-Day 28)/Baseline]. Standard deviation is reported as a percentage. | Baseline and Day 28 |
| Number of Participants Who Experienced an Adverse Event | An adverse event was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or disease temporally associated with the use of the study drug or a study procedure, whether or not considered related to the study drug or study procedure. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse event. | Up to 42 days |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | An adverse event was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or disease temporally associated with the use of the study drug or a study procedure, whether or not considered related to the study drug or study procedure. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse event. | Up to 28 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | MK-8892 | MK-8892 once daily for 28 days titrated to the highest tolerated dose per participant (up to 4 mg). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | MK-8892 | MK-8892 once daily for 28 days titrated to the highest tolerated dose per participant (up to 4 mg). |
| 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 |
| 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 | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage Change From Baseline in Pulmonary Vascular Resistance (PVR) | Pulmonary vascular resistance (PVR) is the general pressure which the right ventricle must counteract to pump blood through the lungs. PVR was measured by right heart catheterization performed prior to dosing at baseline (Day 1) and 4 hours postdose on Day 28. Percentage change in PVR from baseline at Day 28 was calculated as [(Baseline-Day 28)/Baseline]. Standard deviation is reported as a percentage. | The population for the efficacy analysis consisted of all participants who completed the 28 days of study. | Posted | Mean | Standard Deviation | Percentage change | Baseline and Day 28 |
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Up to 42 days
All participants who received at least one dose of the investigational drug
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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 | MK-8892 | MK-8892 once daily for 28 days titrated to the highest tolerated dose per participant (up to 4 mg). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Primary | Number of Participants Who Experienced an Adverse Event | An adverse event was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or disease temporally associated with the use of the study drug or a study procedure, whether or not considered related to the study drug or study procedure. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse event. | All participants who received at least one dose of the investigational drug | Posted | Count of Participants | Participants | Up to 42 days |
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|
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| Primary | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | An adverse event was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or disease temporally associated with the use of the study drug or a study procedure, whether or not considered related to the study drug or study procedure. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse event. | All participants who received at least one dose of the investigational drug | Posted | Count of Participants | Participants | Up to 28 days |
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| 0 |
| 4 |
| 0 |
| 4 |
| 0 |
| 4 |
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
| D002318 |
| Cardiovascular Diseases |