Pulmonary Arterial HypertensionPhase 1NCT01926509
Study to Assess the Safety, Tolerability and Pharmacokinetics (PK) of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-005)
A Phase 1 study testing MK-8892 in people with Pulmonary Arterial Hypertension, run by Merck Sharp & Dohme LLC.
Trial summary
This study will evaluate the safety, tolerability, and PK of MK-8892 in participants with pulmonary arterial hypertension. The primary hypothesis is that the geometric mean of MK-8892 area under the concentration time-curve from Hour 0 to 24 hours (AUC0-24hr) in participants with PAH, will be equal to or greater than… 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?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- No sites listed yet
- Study dates
- 14 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
- 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) ≤34 kg/m^2 and a total body weight >40 kg (>88 lbs)
- Has Group 1 pulmonary hypertension (PAH) as defined by the Dana Point 2008 Clinical Classification including: idiopathic PAH (IPAH), Heritable PAH, Drug and toxin-induced PAH, PAH associated with connective tissue disease or congenital heart disease (repaired simple cardiac defects at least 1 year status post corrective surgery, with no residual intracardiac or extracardiac shunt)
- On a stable regimen of background therapy for at least 3 months prior to starting study drug
- Have history of right heart catheterization within two years demonstrating pulmonary arterial hypertension
- Had pulmonary function testing within one year of starting study medication demonstrating total lung capacity (TLC) >70% predicted, forced expiratory volume in 1 second (FEV1) >70% predicted
- Have hemoglobin >75% of the lower limit of the normal range
Who cannot join
- Pulmonary hypertension subtypes including the following according to Dana Point 2008 Clinical Classification: human immunodeficiency virus (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension due to left heart diseases such as systolic dysfunction, diastolic dysfunction or valvular disease, pulmonary hypertension due to lung diseases and/or hypoxia (e.g. chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental abnormalities), chronic thromboembolic pulmonary hypertension (CTEPH), hematologic disorder (myeloproliferative disorders, splenectomy), systemic disorders (sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis), metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders) or other disorder (tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis)
- Have secondary forms of pulmonary hypertension due to pulmonary veno-occlusive disease (PVOD), or pulmonary capillary hemangiomatosis (PCH)
- Resting systolic blood pressure <105 mmHg, or resting heart rate ≥110/min
- Family history of Long QT Syndrome
- Uncorrected hypokalemia or hypomagnesemia
- Taking medications that are potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4) including but not limited to cyclosporine, systemic itraconazole or ketoconazole, glyburide, erythromycin, clarithromycin, or telithromycin, nefazodone, protease inhibitors, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifampicin, St John's wort, diltiazem and verapamil) or has discontinued treatment <3 weeks prior to the start of the study. Concomitant medications, including anticoagulants, angiotensin converting enzyme (ACE) -inhibitors, diuretics, bosentan, ambrisentan and selected calcium channel blockers (e.g., amlodipine) may be allowed at the discretion of the investigator with the concurrence of the Sponsor.
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- Unable to refrain from or anticipates the use of organic nitrates (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol) beginning approximately 2 weeks before start of study and throughout the study
- Unable to refrain from or anticipates the use of prostanoid therapies beginning approximately 2 weeks before start of study and throughout the study
- Consume excessive amounts of alcohol, defined as greater than 3 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 previous 8 weeks
- Participated in another investigational study within 4 weeks
- History of significant multiple and/or severe allergies
- Regular user of illicit drugs, or has a history of drug (including alcohol) abuse, within approximately 6 months
- Pregnant or breast-feeding, or expecting to conceive
- Interstitial lung disease
About this study
Official title: A 28-Day Multiple-Dose Titration Study to Assess the Effects of MK-8892 on Safety, Tolerability and Pharmacokinetics in Subjects With Pulmonary Arterial Hypertension
This study will evaluate the safety, tolerability, and PK of MK-8892 in participants with pulmonary arterial hypertension. The primary hypothesis is that the geometric mean of MK-8892 area under the concentration time-curve from Hour 0 to 24 hours (AUC0-24hr) in participants with PAH, will be equal to or greater than the efficacious exposure in humans of 0.6 μM•hr.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- MK-8892, Placebo for 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
Placebo for MK-8892Drug
| Study group | Role | What they receive |
|---|---|---|
| MK-8892 Panel A | Experimental | Participants will be administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28). Receives: Drug: MK-8892 |
| MK-8892 Panel B | Experimental | Participants will be administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28). Receives: Drug: MK-8892 |
| MK-8892 Panel C | Experimental | Participants will be administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28). Receives: Drug: MK-8892 |
| Placebo (Panels A and B) | Placebo comparator | Participants will be administered placebo to MK-8892 once daily for 28 days. Receives: Drug: Placebo for MK-8892 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 at Day 1 and Day 28
Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose on Days 1 and 28 to determine the AUC0-24hr.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours postdose on Days 1 and 28
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants that reported at least 1 AE was summarized.
Measured: Up to 42 days
Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants who had study drug discontinued due to an AE was summarized.
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 posted21 Aug 2013 (estimated)
- Study start14 Nov 2013
- Primary completion1 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 23 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
- NCT01926509
- Sponsor's protocol ID
- 8892-005
- Other IDs
- 2013-002529-51, MK-8892-005
- Status last verified
- May 2018
- First submitted
- 19 Aug 2013
- Last updated
- 3 Dec 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 3 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 28-Day Multiple-Dose Titration Study to Assess the Effects of MK-8892 on Safety, Tolerability and Pharmacokinetics in Subjects With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01926509
- Acronym / sponsor ID
- 8892-005
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 14 Nov 2013 (actual)
- Primary completion
- 1 Sep 2014 (actual)
- Study completion
- 8 Sep 2014 (actual)
- First posted
- 21 Aug 2013 (estimated)
- Results
- Posted 3 Dec 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 evaluate the safety, tolerability, and PK of MK-8892 in participants with pulmonary arterial hypertension. The primary hypothesis is that the geometric mean of MK-8892 area under the concentration time-curve from Hour 0 to 24 hours (AUC0-24hr) in participants with PAH, will be equal to or greater than the efficacious exposure in humans of 0.6 μM•hr.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MK-8892 Panel A | Experimental | Drug: MK-8892Participants will be administered MK-8892 once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 3 mg (Days 15-21), 4 mg (Days 22-28). |
| MK-8892 Panel B | Experimental | Drug: MK-8892Participants will be administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), 4 mg (Days 22-28). |
| MK-8892 Panel C | Experimental | Drug: MK-8892Participants will be administered MK-8892 orally, once daily at following dose levels: 1 mg (Days 1-7), 2 mg (Days 8-14), 4 mg (Days 15-21), up to 8 mg (Days 22-28). |
| Placebo (Panels A and B) | Placebo comparator | Drug: Placebo for MK-8892Participants will be administered placebo to MK-8892 once daily for 28 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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) ≤34 kg/m^2 and a total body weight >40 kg (>88 lbs)
- Has Group 1 pulmonary hypertension (PAH) as defined by the Dana Point 2008 Clinical Classification including: idiopathic PAH (IPAH), Heritable PAH, Drug and toxin-induced PAH, PAH associated with connective tissue disease or congenital heart disease (repaired simple cardiac defects at least 1 year status post corrective surgery, with no residual intracardiac or extracardiac shunt)
- On a stable regimen of background therapy for at least 3 months prior to starting study drug
- Have history of right heart catheterization within two years demonstrating pulmonary arterial hypertension
Key exclusion criteria (15 listed)
- Pulmonary hypertension subtypes including the following according to Dana Point 2008 Clinical Classification: human immunodeficiency virus (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension due to left heart diseases such as systolic dysfunction, diastolic dysfunction or valvular disease, pulmonary hypertension due to lung diseases and/or hypoxia (e.g. chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental abnormalities), chronic thromboembolic pulmonary hypertension (CTEPH), hematologic disorder (myeloproliferative disorders, splenectomy), systemic disorders (sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis), metabolic disorders (glycogen storage disease, Gaucher disease, thyroid disorders) or other disorder (tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis)
- Have secondary forms of pulmonary hypertension due to pulmonary veno-occlusive disease (PVOD), or pulmonary capillary hemangiomatosis (PCH)
- Resting systolic blood pressure <105 mmHg, or resting heart rate ≥110/min
- Family history of Long QT Syndrome
- Uncorrected hypokalemia or hypomagnesemia
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 Panel A, MK-8892 Panel B, MK-8892 Panel C |
| Placebo for MK-8892 | Drug | Placebo (Panels A and B) |
Primary outcome
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 at Day 1 and Day 28
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours postdose on Days 1 and 28
Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose on Days 1 and 28 to determine the AUC0-24hr.
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to 42 days
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants that reported at least 1 AE was summarized.
Number of Participants Who Had Study Drug Discontinued Due to an Adverse Event
Time frame: Up to 28 days
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The number of participants who had study drug discontinued due to an AE was summarized.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 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 7 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: finished, as of the sponsor's last update on 3 Dec 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. Some participants in this study may receive a placebo. 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 3 Dec 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?
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 at Day 1 and Day 28 (time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24 hours postdose on Days 1 and 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 3 Dec 2018.