Pulmonary HypertensionPhase 1NCT02078557
A Multiple Dose Titration Study of MK-8892 in Participants With Pulmonary Hypertension and Left Heart Disease (MK-8892-007)
A Phase 1 study testing MK-8892 in people with Pulmonary Hypertension and Left Heart Disease, run by Merck Sharp & Dohme LLC.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pulmonary Hypertension, Left Heart Disease
- What is being tested?
- MK-8892
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- No sites listed yet
- Study dates
- 9 May 2014to 10 Sep 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pulmonary hypertension (out of proportion, PHOOP) and heart failure with reduced left ventricular ejection fraction (PHOOP/rEF)
- If female, cannot be pregnant or breastfeeding. Females of reproductive potential must agree to agree to use (and/or have their partner use) two (2) acceptable methods of birth control throughout the study and until 2 weeks after the last dose of study drug is administered
- Body mass index (BMI) <=35 kg/m^2 and and <=18 kg/m^2
- Has World Health Organization (WHO) Group 2 pulmonary hypertension (PAH)
- Stable heart failure on optimal medical therapy with no hospitalizations for congestion due to heart failure within the previous 3 months
Who cannot join
- Primary pulmonary arterial hypertension or veno-occlusive disease (WHO Group 1), or pulmonary hypertension secondary to other causes (WHO Groups 3 -5) including but not limited to autoimmune disease, connective tissue disease, and Eisenmenger syndrome
- Currently treatment with or anticipates use of nitrate, phosphodiesterase type 5 (PDE5) inhibitor, or medications known to induce or inhibit cytochrome P450 3A4 (CYP3A4) metabolism, and cannot be transitioned off of this therapy for >=7 days prior to dosing and through completion of this study
- Symptoms of coronary artery disease requiring therapy with nitrates, within the past 3 months
- Severe aortic or mitral stenosis, or severe aortic, mitral, or tricuspid insufficiency.
- Significant carotid artery disease
- Restrictive, infiltrative (e.g., amyloidosis) or hypertrophic cardiomyopathy
Show all 15Show fewer
- Mentally or legally institutionalized or incapacitated, has significant emotional problems at the time of pre study (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 years. Subjects who have had situational depression may be enrolled in the study at the discretion of the investigator.
- History of stroke, chronic seizures, or major neurological disorder
- History of clinically significant endocrine (not including diabetes mellitus), gastrointestinal, hematological, hepatic (not including chronic Hepatitis C), immunological (not including chronic human immunodeficiency virus [HIV]), respiratory, or genitourinary abnormalities or diseases. Participants with a history of childhood asthma may be enrolled in the study at the discretion of the investigator. Participants with controlled hypertension are allowed to be enrolled.
- Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the dose of study drug, throughout the study (including washout intervals between treatment periods), until the post study visit. There may be certain medications that will be permitted.
- Consumes excessive amounts of alcohol, defined as greater than 5 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
- Major surgery or donated blood within 8 weeks prior to the pre study (screening) visit
- Participated in another investigational study within 4 weeks prior to the pre study (screening) visit
- History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
- Uses illicit drugs or has a history of drug (including alcohol) abuse within the past 6 months
About this study
Official title: A Multiple Dose Titration Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892 in Patients With Pulmonary Hypertension and Left Heart Disease
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.
- Conditions
- Pulmonary Hypertension, Left Heart Disease
- Being tested
- MK-8892
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8892Drug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: MK-8892 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study start9 May 2014
- Primary completion15 Aug 2014
- Study completion10 Sep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02078557
- Sponsor's protocol ID
- 8892-007
- Other IDs
- 2013-004639-55, MK-8892-007
- Status last verified
- Mar 2018
- First submitted
- 3 Mar 2014
- Last updated
- 31 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multiple Dose Titration Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892 in Patients With Pulmonary Hypertension and Left Heart Disease
- ClinicalTrials.gov ID
- NCT02078557
- Acronym / sponsor ID
- 8892-007
- Conditions
- Pulmonary Hypertension, Left Heart Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 9 May 2014 (actual)
- Primary completion
- 15 Aug 2014 (actual)
- Study completion
- 10 Sep 2014 (actual)
- First posted
- 5 Mar 2014 (estimated)
- Results
- Posted 31 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MK-8892 | Experimental | Drug: MK-8892Starting 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Pulmonary hypertension (out of proportion, PHOOP) and heart failure with reduced left ventricular ejection fraction (PHOOP/rEF)
- If female, cannot be pregnant or breastfeeding. Females of reproductive potential must agree to agree to use (and/or have their partner use) two (2) acceptable methods of birth control throughout the study and until 2 weeks after the last dose of study drug is administered
- Body mass index (BMI) <=35 kg/m^2 and and <=18 kg/m^2
- Has World Health Organization (WHO) Group 2 pulmonary hypertension (PAH)
- Stable heart failure on optimal medical therapy with no hospitalizations for congestion due to heart failure within the previous 3 months
Key exclusion criteria (15 listed)
- Primary pulmonary arterial hypertension or veno-occlusive disease (WHO Group 1), or pulmonary hypertension secondary to other causes (WHO Groups 3 -5) including but not limited to autoimmune disease, connective tissue disease, and Eisenmenger syndrome
- Currently treatment with or anticipates use of nitrate, phosphodiesterase type 5 (PDE5) inhibitor, or medications known to induce or inhibit cytochrome P450 3A4 (CYP3A4) metabolism, and cannot be transitioned off of this therapy for >=7 days prior to dosing and through completion of this study
- Symptoms of coronary artery disease requiring therapy with nitrates, within the past 3 months
- Severe aortic or mitral stenosis, or severe aortic, mitral, or tricuspid insufficiency.
- Significant carotid artery disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-8892 | Drug | MK-8892 |
Primary outcome
Percentage Change From Baseline in Pulmonary Vascular Resistance (PVR)
Time frame: Baseline and Day 28
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.
Number of Participants Who Experienced an Adverse Event
Time frame: Up to 42 days
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.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
Time frame: Up to 28 days
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-8892 in people with Pulmonary Hypertension and Left Heart Disease, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change From Baseline in Pulmonary Vascular Resistance (PVR) (time frame: Baseline and Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2018.