Pulmonary Arterial HypertensionPhase 1NCT01934647
Acute Dosing of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-003)
A Phase 1 study testing MK-8892 in people with Pulmonary Arterial Hypertension, run by Merck Sharp & Dohme LLC.
Trial summary
This clinical trial will study the safety, tolerability, and pharmacodynamics of single doses of MK-8892 in participants with pulmonary arterial hypertension (PAH). The primary objective is to estimate the measured peak effect of the highest acutely tolerated (HAT) single oral dose of MK-8892 on pulmonary vascular… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- 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
- 7 participants
- Where
- No sites listed yet
- Study dates
- 22 Nov 2013to 8 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- postmenopausal female or if female of reproductive potential, remains abstinent or uses two acceptable methods of birth control during 14 days after dosing with MK-8892
- has suspected PAH classified in one of the following sub-groups: idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease, as defined by the Dana Point 2008 Clinical Classification
- has a clinical indication for right heart catheterization
- PAH classified as World Health Organization (WHO) functional class II or III
Who cannot join
- has a medical history indicating a secondary cause of Pulmonary Hypertension (PH) or a non-included etiology of PAH including the following tests within 6 months of Visit 1: Echo indicating significant left heart disease, valvular disease, or structural defects; function test indicating significant pulmonary disease; imaging test indicating veno-occlusive disease; perfusion scan indicating thromboembolic disease; abdominal ultrasound indicating cirrhosis; positive test for human immunodeficiency virus (HIV)
- has persistent or permanent atrial fibrillation, significantly impaired gas exchange, history of radiation of the lung or mediastinum, hepatic or hepatobiliary disease, immunodeficiencies or latent bleeding risk
- has estimated Glomerular Filtration Rate (GFR) <45 mL/min
- has alanine aminotransferase test (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate aminotransferase test (AST) serum glutamic oxaloacetic transaminase (SGOT) >= 3 x upper limit of normal (ULN) at Visit 1
- has a systolic blood pressure (BP) <105 mmHg, or heart rate (HR) > 100 beats/min at Visit 1 (Day -7 to -1)
- has previously received specific therapy for PAH within 4 weeks prior to Visit 1
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- has taken sildenafil, valdenafil or a nitrate within 24 hours prior to Visit 2 date
- has taken tadalafil within 7 days prior to Visit 2 date
- has taken 2 or more specific PAH medications concomitantly within 4 weeks of anticipated Visit 2 date. Only treatment naïve subjects or subjects on stable PAH-specific monotherapy with an endothelin receptor antagonist ([ERA]; bosentan, ambrisentan, or macitentan) or a prostacyclin analog ([PCA]; treprostinil, epoprostenol, or iloprost) are eligible. PAH monotherapy with one of these medications may continue without interruption during this study
- has taken a soluble guanylate cyclase (sGC) activator (riociguat) within 24 hours of anticipated Visit 2 date.
- has taken diltiazem immediate release within 1 day or diltiazem extended release within 2 days prior to Visit 2 date
- is currently taking potent inhibitors or inducers of Cytochrome P450 3A4 (CYPA4), or is consuming >1 liter of grapefruit juice per day
- is pregnant or breastfeeding or expecting to conceive during study or post study follow-up period
- has donated 500 mL of blood within prior 60 days
- is currently participating in or has within the prior three months participated in a study with an investigational compound or device
About this study
Official title: A Non-randomized, Single-Panel, Open-Label Trial to Study the Safety, Tolerability and Pharmacodynamics of MK-8892 Acute Dosing in Subjects With Moderate to Severe Pulmonary Arterial Hypertension
This clinical trial will study the safety, tolerability, and pharmacodynamics of single doses of MK-8892 in participants with pulmonary arterial hypertension (PAH). The primary objective is to estimate the measured peak effect of the highest acutely tolerated (HAT) single oral dose of MK-8892 on pulmonary vascular resistance (PVR).
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- MK-8892
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8892Drug
Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892
| Study group | Role | What they receive |
|---|---|---|
| 1 mg MK-8892 | Experimental | Participants will receive a single oral dose of 1 mg MK-8892. Receives: Drug: MK-8892 |
| 4 mg MK-8892 | Experimental | Participants will receive a single oral dose of 4 mg MK-8892. Receives: Drug: MK-8892 |
| 8 mg MK-8892 | Experimental | Participants will receive a single oral dose of 8 mg MK-8892. Receives: Drug: MK-8892 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892
PVR assessments were performed throughout the right heart catheterization (RHC). Peak PVR reduction was determined to occur if 2 consecutive PVR measurements were at least 20% greater than the nadir PVR measurement.
Measured: Baseline and up to 5 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2013 (estimated)
- Study start22 Nov 2013
- Primary completion8 Sep 2014
- Study completion8 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 Arterial 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 7 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
- NCT01934647
- Sponsor's protocol ID
- 8892-003
- Other IDs
- 2013-001680-23, MK-8892-003
- Status last verified
- Mar 2018
- First submitted
- 30 Aug 2013
- Last updated
- 22 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 22 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-randomized, Single-Panel, Open-Label Trial to Study the Safety, Tolerability and Pharmacodynamics of MK-8892 Acute Dosing in Subjects With Moderate to Severe Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01934647
- Acronym / sponsor ID
- 8892-003
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 22 Nov 2013 (actual)
- Primary completion
- 8 Sep 2014 (actual)
- Study completion
- 8 Sep 2014 (actual)
- First posted
- 4 Sep 2013 (estimated)
- Results
- Posted 22 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 clinical trial will study the safety, tolerability, and pharmacodynamics of single doses of MK-8892 in participants with pulmonary arterial hypertension (PAH). The primary objective is to estimate the measured peak effect of the highest acutely tolerated (HAT) single oral dose of MK-8892 on pulmonary vascular resistance (PVR).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 mg MK-8892 | Experimental | Drug: MK-8892Participants will receive a single oral dose of 1 mg MK-8892. |
| 4 mg MK-8892 | Experimental | Drug: MK-8892Participants will receive a single oral dose of 4 mg MK-8892. |
| 8 mg MK-8892 | Experimental | Drug: MK-8892Participants will receive a single oral dose of 8 mg MK-8892. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- postmenopausal female or if female of reproductive potential, remains abstinent or uses two acceptable methods of birth control during 14 days after dosing with MK-8892
- has suspected PAH classified in one of the following sub-groups: idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease, as defined by the Dana Point 2008 Clinical Classification
- has a clinical indication for right heart catheterization
- PAH classified as World Health Organization (WHO) functional class II or III
Key exclusion criteria (15 listed)
- has a medical history indicating a secondary cause of Pulmonary Hypertension (PH) or a non-included etiology of PAH including the following tests within 6 months of Visit 1: Echo indicating significant left heart disease, valvular disease, or structural defects; function test indicating significant pulmonary disease; imaging test indicating veno-occlusive disease; perfusion scan indicating thromboembolic disease; abdominal ultrasound indicating cirrhosis; positive test for human immunodeficiency virus (HIV)
- has persistent or permanent atrial fibrillation, significantly impaired gas exchange, history of radiation of the lung or mediastinum, hepatic or hepatobiliary disease, immunodeficiencies or latent bleeding risk
- has estimated Glomerular Filtration Rate (GFR) <45 mL/min
- has alanine aminotransferase test (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate aminotransferase test (AST) serum glutamic oxaloacetic transaminase (SGOT) >= 3 x upper limit of normal (ULN) at Visit 1
- has a systolic blood pressure (BP) <105 mmHg, or heart rate (HR) > 100 beats/min at Visit 1 (Day -7 to -1)
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-8892Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892 | Drug | 1 mg MK-8892, 4 mg MK-8892, 8 mg MK-8892 |
Primary outcome
Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892
Time frame: Baseline and up to 5 hours post-dose
PVR assessments were performed throughout the right heart catheterization (RHC). Peak PVR reduction was determined to occur if 2 consecutive PVR measurements were at least 20% greater than the nadir PVR measurement.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 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 Arterial Hypertension, 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 4 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 22 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 22 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?
Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892 (time frame: Baseline and up to 5 hours post-dose). 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 22 Oct 2018.