A Single Rising Dose Study of MK-8150 (MK-8150-001)

Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Single Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150

ClinicalTrials.gov ID

NCT01590810

Acronym / sponsor ID

8150-001

Conditions

Hypertension, Isolated Systolic Hypertension (ISH)

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

34 participants (actual)

Lead sponsor

Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)

Study start

7 May 2012 (actual)

Primary completion

24 Jan 2013 (actual)

Study completion

5 Feb 2013 (actual)

First posted

3 May 2012 (estimated)

Results

Posted 27 Jun 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Double blind (participant, investigator)

Number of arms

4

Who may qualify

Ages

18 to 60 years

Sex

Male only

Healthy volunteers

Accepted

Age groups

Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With an Adverse Event (AE)

   Time frame: Up to 14 days after the last dose (Up to approximately 42 days)

   An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.

2. Number of Participants Who Discontinued Study Due to an AE

   Time frame: Up to 14 days after the last dose (Up to approximately 42 days)

   An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the study drug, is also an AE.

3. Change From Baseline in Time-weighted Average Across 24 Hours (TWA0-24hrs) cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

   Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

   cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

4. Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

   Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

   cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

5. Change From Baseline in TWA0-24hrs cSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

   Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

   cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

6. Change From Baseline in TWA0-24hrs cSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

   Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

   cSBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cSBP value by that cSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

7. Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

   Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose; except Period 1: Pre-dose and 2, 4, 12 and 24 hours post dose

   AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. 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. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

8. Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

   Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

   AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. 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. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

9. Change From Baseline in TWA0-24hrs AIx in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

   Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

   AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. 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. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

10. Change From Baseline in TWA0-24hrs AIx in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

    Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

    AIx was measured by applanation tonometry of the radial artery, using the SphygmoCor System. 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. Time-weighted average was obtained as follows: For all AIx values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each AIx value by that AIx value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified AIx value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement. AIx was adjusted for HR.

11. Change From Baseline in Time-weighted Average Across 12 Hours (TWA0-12hrs) HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

12. Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

13. Change From Baseline in TWA0-12hrs HR in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

14. Change From Baseline in TWA0-12hrs HR in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours post dose

    HR was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all HR values obtained over the 12-hour observation period, multiply the length of time that the participant spent at each HR value by that HR value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified HR value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

15. Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

    Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

16. Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

    Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

17. Change From Baseline in TWA0-24hrs cDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

    Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

18. Change From Baseline in TWA0-24hrs cDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

    Time frame: Pre-dose and 2, 3, 4, 6, 8, 12, 16 and 24 hours post dose

    cDBP was measured by applanation tonometry of the radial artery, using the SphygmoCor System. The central pressure waveform was determined from the peripheral pressure waveform by a transfer function. Time-weighted average was obtained as follows: For all cDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each cDBP value by that cDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified cDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

19. Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

20. Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

21. Change From Baseline in TWA0-24hrs pSBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

22. Change From Baseline in TWA0-24hrs pSBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pSBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pSBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pSBP value by that pSBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pSBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

23. Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel A)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

24. Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel B)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

25. Change From Baseline in TWA0-24hrs pDBP in Male Participants With Mild to Moderate Hypertension Administered Single Doses of MK-8150 and Placebo (Panel C)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

26. Change From Baseline in TWA0-24hrs pDBP in Healthy Male Participants Administered Single Doses of MK-8150 and Placebo (Panel D)

    Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16 and 24 hours post dose

    pDBP was measured with a validated automatic measuring device. Time-weighted average was obtained as follows: For all pDBP values obtained over the 24-hour observation period, multiply the length of time that the participant spent at each pDBP value by that pDBP value, add these products together, and then divide by duration of the observation period. The length of time spent at an identified pDBP value was defined as the time elapsed since previous post-dose measurement, or time elapsed since drug administration, if there is no previous post-dose measurement.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2018.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Results publication: PubMed 27561272Knox CD, de Kam PJ, Azer K, Wong P, Ederveen AG, Shevell D, Morabito C, Meehan AG, Liu W, Reynders T, Denef JF, Mitselos A, Jonathan D, Gutstein DE, Mitra K, Sun SY, Lo MM, Cully D, Ali A. Discovery and Clinical Evaluation of MK-8150, A Novel Nitric Oxide Donor With a Unique Mechanism of Nitric Oxide Release. J Am Heart Assoc. 2016 Aug 25;5(9):e003493. doi: 10.1161/JAHA.116.003493.
• Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/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.