Pulmonary Arterial HypertensionPhase 1NCT01798849
A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)
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 safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C). Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- MK-8892
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- 15 Mar 2013to 17 Jul 2013
- 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 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Systolic blood pressure (SBP) > 110 and ≤ 140 mmHg for Panels A and B, SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication
- Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 32 kg/m^2
- Healthy (with the exception of hypertensive subjects in Panel C)
- No clinically significant abnormality on electrocardiogram (ECG)
- No history of clinically significant cardiac disease
- No history of heart failure
- Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months
Who cannot join
- Mentally or legally incapacitated
- History of stroke, chronic seizures, or major neurological disorder
- History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
- Functional disability that can interfere with rising from a sitting position to the standing position
- History of cancer (malignancy)
- History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
Show all 16Show fewer
- Positive for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)
- Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
- Has participated in another investigational trial within 4 weeks
- Unable to refrain from or anticipates the use of any medication during the study
- Anticipates using medication for erectile dysfunction during the study
- Uses or anticipates using organic nitrates during the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)
- Anticipates using cytochrome P450 inhibitors (e.g. ketoconazole) or inducers (e.g. rifampin) during the study
- Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages per day
- Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day
- Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year
About this study
Official title: A Single Rising Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892
This study will evaluate safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).
Read the detailed description
Up to three planned panels of either 8 healthy participants (Panels A and B) or 8 participants with mild to moderate hypertension (Panel C) will be enrolled. In Panels A and B, 8 participants will alternately receive single rising doses of MK-8892 or placebo. All doses will be administered in the fasted state, except Panel A, Period 5 in which a standard high-fat breakfast provided approximately 30 minutes prior to dosing.
Panel A will begin first. At least 3 days will elapse before participants in the alternate panel (Panel B) will receive the next higher dose. In Panel C, 8 mild to moderate hypertensive male participants will receive single rising doses of MK-8892 or placebo. Panel C may begin after the first 4 periods of Panels A and B have completed dosing. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. Subsequent doses in any panel will be administered only after careful evaluation of safety, tolerability, and pharmacodynamic effects of a given dose. All participants in periods of all panels (with exception of 2.0 mg fasted/fed periods) will be randomly assigned to either study drug or placebo, i.e a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants will receive 2.0 mg MK-8892 in a fasted and fed state.The 2.0 mg MK-8892 fed/fasted data will be utilized for pharmacokinetic comparison and only the 2.0 mg MK-8892 fasted data will utilized for the analysis of the pharmacodynamics endpoints.
In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥1 hour, dose escalation in that participant will be halted and the participant may be withdrawn from the study or rechallenged at same dose or at a lower dose. Paricipants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.
- 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 |
|---|---|---|
| Panel A-Healthy | Experimental | Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, 14 mg or 2.0 mg fed, and 2 participants received placebo. Dosing periods will alternate with Panel B. Receives: Drug: MK-8892; Drug: Placebo for MK-8892 |
| Panel B-Healthy | Experimental | Within each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods will alternate with Panel A. Receives: Drug: MK-8892; Drug: Placebo for MK-8892 |
| Panel C-Mild/Moderate Hypertension | Experimental | Within each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages will be determined by the results of Panels A and B. Receives: Drug: MK-8892; Drug: Placebo for MK-8892 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants
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, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Measured: up to 7 weeks
Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants
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, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Measured: up to 7 weeks
Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants
Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Measured: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants
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 percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Measured: up to 7 weeks
Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants
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 percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Measured: up to 7 weeks
Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants
Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Measured: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period)
Secondary outcomes (23)
Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants
Peripheral diastolic blood pressure was measured using a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Measured: Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants
Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Measured: Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants
AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours.
Measured: Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants
Peripheral blood pressure assessments were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose by using a validated automatic measuring device. Peripheral diastolic blood pressure was measured a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.
Measured: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants
Heart rate was measured predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose by a validated automatic measuring device. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.
Measured: Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)
TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants
AIx was measured by applanation tonometry of the radial artery. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Augmentation index is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness. The time-weighted average change from baseline was calculated by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. Negative number indicates a decrease.
Measured: Predose to 24 hours Postdose (for each Dosing Period of Each Panel)
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Healthy Participants
Blood samples taken at Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr.
Measured: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Healthy Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892 - Healthy Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Maximum Concentration (Cmax) of MK-8892 - Healthy Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Time to Cmax (Tmax) of MK-8892 - Healthy Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Apparent Terminal Half-life (t1/2) of MK-8892 - Healthy Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Hypertensive Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Hypertensive Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892- Hypertensive Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Maximum Concentration (Cmax) of MK-8892- Hypertensive Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Time to Cmax (Tmax) of MK-8892- Hypertensive Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Tmax.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Apparent Terminal Half-life (t1/2) of MK-8892- Hypertensive Participants
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of 2.0 mg MK-8892-Healthy Participants-Fasted/Fed
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose of each dosing period to determine the AUC0-24hr. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-last. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the AUC0-inf. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Maximum Concentration (Cmax) of 2.0 mg MK-8892 - Healthy Participants- Fasted/Fed
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the Cmax. A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Apparent Terminal Half-life (t1/2) of 2.0 mg MK-8892 - Healthy Participants -Fasted/Fed
Blood samples taken at Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose of each dosing period to determine the t1/2.A mixed effects model with Cohort (Healthy or hypertensive) as a fixed term, participant as a random effect was used for summary data. For participants that participated in Period 5, study drug was administered after a standard high-fat breakfast provided approximately 30 minutes prior to dosing. The meal was consumed in a 20-minute period with start and stop times being recorded. Participants were administered a single dose of MK-8892 or matching placebo Within 10 minutes of completing the meal.
Measured: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2013 (estimated)
- Study start15 Mar 2013
- Primary completion17 Jul 2013
- Study completion17 Jul 2013
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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01798849
- Sponsor's protocol ID
- 8892-001
- Other IDs
- 2012-005472-34
- Status last verified
- May 2019
- First submitted
- 22 Feb 2013
- Last updated
- 22 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Rising Dose Clinical Trial to Study the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8892
- ClinicalTrials.gov ID
- NCT01798849
- Acronym / sponsor ID
- 8892-001
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 15 Mar 2013 (actual)
- Primary completion
- 17 Jul 2013 (actual)
- Study completion
- 17 Jul 2013 (actual)
- First posted
- 26 Feb 2013 (estimated)
- Results
- Posted 22 Jul 2019
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 safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).
Detailed description
Up to three planned panels of either 8 healthy participants (Panels A and B) or 8 participants with mild to moderate hypertension (Panel C) will be enrolled. In Panels A and B, 8 participants will alternately receive single rising doses of MK-8892 or placebo. All doses will be administered in the fasted state, except Panel A, Period 5 in which a standard high-fat breakfast provided approximately 30 minutes prior to dosing.
Panel A will begin first. At least 3 days will elapse before participants in the alternate panel (Panel B) will receive the next higher dose. In Panel C, 8 mild to moderate hypertensive male participants will receive single rising doses of MK-8892 or placebo. Panel C may begin after the first 4 periods of Panels A and B have completed dosing. For all panels, there will be at least 7 days washout between treatment periods for any given participant. Participants may only be enrolled in one panel of the study. Subsequent doses in any panel will be administered only after careful evaluation of safety, tolerability, and pharmacodynamic effects of a given dose. All participants in periods of all panels (with exception of 2.0 mg fasted/fed periods) will be randomly assigned to either study drug or placebo, i.e a participant could be assigned to receive study drug in one period and placebo in another. As per the protocol allocation plan, the same participants will receive 2.0 mg MK-8892 in a fasted and fed state.The 2.0 mg MK-8892 fed/fasted data will be utilized for pharmacokinetic comparison and only the 2.0 mg MK-8892 fasted data will utilized for the analysis of the pharmacodynamics endpoints.
In addition, during any of the treatment periods if a participant demonstrates change in any one of the protocol-defined parameters lasting ≥1 hour, dose escalation in that participant will be halted and the participant may be withdrawn from the study or rechallenged at same dose or at a lower dose. Paricipants that meet criteria listed will be followed up until parameters no longer meet stopping rule criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Panel A-Healthy | Experimental | Drug: MK-8892, Drug: Placebo for MK-8892Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, 14 mg or 2.0 mg fed, and 2 participants received placebo. Dosing periods will alternate with Panel B. |
| Panel B-Healthy | Experimental | Drug: MK-8892, Drug: Placebo for MK-8892Within each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods will alternate with Panel A. |
| Panel C-Mild/Moderate Hypertension | Experimental | Drug: MK-8892, Drug: Placebo for MK-8892Within each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages will be determined by the results of Panels A and B. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Systolic blood pressure (SBP) > 110 and ≤ 140 mmHg for Panels A and B, SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication
- Body Mass Index (BMI) ≥ 18 kg/m^2 and ≤ 32 kg/m^2
- Healthy (with the exception of hypertensive subjects in Panel C)
- No clinically significant abnormality on electrocardiogram (ECG)
- No history of clinically significant cardiac disease
Key exclusion criteria (16 listed)
- Mentally or legally incapacitated
- History of stroke, chronic seizures, or major neurological disorder
- History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
- Functional disability that can interfere with rising from a sitting position to the standing position
- History of cancer (malignancy)
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 | Panel A-Healthy, Panel B-Healthy, Panel C-Mild/Moderate Hypertension |
| Placebo for MK-8892 | Drug | Panel A-Healthy, Panel B-Healthy, Panel C-Mild/Moderate Hypertension |
Primary outcome
Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants
Time frame: up to 7 weeks
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, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants
Time frame: up to 7 weeks
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, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants
Time frame: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants
Time frame: up to 7 weeks
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 percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants
Time frame: up to 7 weeks
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 percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.
Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants
Time frame: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period)
Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.
23 secondary outcomes
Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants
Time frame: Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants
Time frame: Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants
Time frame: Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants
Time frame: Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)
Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants
Time frame: Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)
TWA0-24hr for Augmentation Index (AIx) - Hypertensive Participants
Time frame: Predose to 24 hours Postdose (for each Dosing Period of Each Panel)
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Healthy Participants
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Healthy Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892 - Healthy Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Maximum Concentration (Cmax) of MK-8892 - Healthy Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Time to Cmax (Tmax) of MK-8892 - Healthy Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Apparent Terminal Half-life (t1/2) of MK-8892 - Healthy Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of MK-8892 - Hypertensive Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of MK-8892 - Hypertensive Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of MK-8892- Hypertensive Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Maximum Concentration (Cmax) of MK-8892- Hypertensive Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Time to Cmax (Tmax) of MK-8892- Hypertensive Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Apparent Terminal Half-life (t1/2) of MK-8892- Hypertensive Participants
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to 24 Hours (AUC0-24hr) of 2.0 mg MK-8892-Healthy Participants-Fasted/Fed
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, and 24 hours postdose
Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Plasma Concentration Time Point (AUC0-last) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Area Under the Concentration Time-curve From Hour 0 to Infinity (AUC0-inf) of 2.0 mg MK-8892 - Healthy Participants-Fasted/Fed
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Maximum Concentration (Cmax) of 2.0 mg MK-8892 - Healthy Participants- Fasted/Fed
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Apparent Terminal Half-life (t1/2) of 2.0 mg MK-8892 - Healthy Participants -Fasted/Fed
Time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, and 96 hours postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 16 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 22 Jul 2019. 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 Jul 2019). 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 of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants (time frame: up to 7 weeks). The study lists 6 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 22 Jul 2019.