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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01590810
First received: May 1, 2012
Last updated: September 8, 2016
Last verified: September 2016
Results First Received: March 3, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Hypertension
Isolated Systolic Hypertension (ISH)
Interventions: Drug: MK-8150 2.0 mg
Drug: MK-8150 10 mg
Drug: MK-8150 40 mg
Drug: MK-8150 90 mg
Drug: MK-8150 5.0 mg
Drug: MK-8150 20 mg
Drug: MK-8150 60 mg
Drug: MK-8150 120 mg
Drug: MK-8150 160 mg
Drug: MK-8150 320 mg
Drug: MK-8150 600 mg
Drug: MK-8150 900 mg
Drug: MK-8150 1200 mg
Drug: Placebo for MK-8150
Drug: MK-8150 50 mg
Drug: MK-8150 100 mg
Drug: MK-8150 200 mg
Drug: MK-8150 400 mg
Drug: MK-8150 500 mg

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Panel A – MK-8150 2 to 90 mg/Placebo Within each of the up to 5 treatment periods in Panel A, 6 healthy participants were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel A was 2 mg to 90 mg.
Panel B – MK-8150 4 to 120 mg/Placebo Within each of the up to 5 treatment periods in Panel B, 6 healthy participants were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel B was 4 mg to 120 mg.
Panel C – MK-8150 5 to 90 mg/Placebo Within each of the up to 5 treatment periods in Panel C, 6 participants with mild to moderate hypertension were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel C was 5 mg to 90 mg.
Panel D – MK-8150 50 to 200 mg Description: Within Panel D, 8 healthy participants were randomly assigned to receive single doses of MK-8150, and 2 were randomly assigned to receive single administrations of matching placebo throughout the up to 5 treatment periods according to a computer-generated allocation schedule (i.e., assignment of a participant to either MK-8150 or placebo was fixed for all Panel D periods). This reporting group presents data for the Panel D participants administered MK-8150. The dose range of MK-8150 administered for Panel D was 50 mg to 200 mg.
Panel D – Placebo Within Panel D, 8 healthy participants were randomly assigned to receive single doses of MK-8150, and 2 were randomly assigned to receive single administrations of matching placebo throughout the up to 5 treatment periods according to a computer-generated allocation schedule (i.e., assignment of a participant to either MK-8150 or placebo was fixed for all Panel D periods). This reporting group presents data for the Panel D participants administered placebo.

Participant Flow:   Overall Study
    Panel A – MK-8150 2 to 90 mg/Placebo   Panel B – MK-8150 4 to 120 mg/Placebo   Panel C – MK-8150 5 to 90 mg/Placebo   Panel D – MK-8150 50 to 200 mg   Panel D – Placebo
STARTED   8   8   8   8   2 
COMPLETED   8   7   7   8   2 
NOT COMPLETED   0   1   1   0   0 
Physician Decision                0                1                1                0                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Panel A – MK-8150 2 to 90 mg/Placebo Within each of the up to 5 treatment periods in Panel A, 6 healthy participants were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel A was 2 mg to 90 mg.
Panel B – MK-8150 4 to 120 mg/Placebo Within each of the up to 5 treatment periods in Panel B, 6 healthy participants were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel B was 4 mg to 120 mg.
Panel C – MK-8150 5 to 90 mg/Placebo Within each of the up to 5 treatment periods in Panel C, 6 participants with mild to moderate hypertension were randomly assigned to receive a single dose of MK-8150, and 2 were randomly assigned to receive single administration of matching placebo according to a computer-generated allocation schedule. By protocol allocation schedule participants did not have fixed assignment to single dose MK-8150 or placebo for all treatment periods, but were reallocated from one treatment period to the next, so that a participant could receive both MK-8150 and placebo, in different periods of the Panel. The dose range of MK-8150 administered for Panel C was 5 mg to 90 mg.
Panel D – MK-8150 50 to 200 mg Description: Within Panel D, 8 healthy participants were randomly assigned to receive single doses of MK-8150, and 2 were randomly assigned to receive single administrations of matching placebo throughout the up to 5 treatment periods according to a computer-generated allocation schedule (i.e., assignment of a participant to either MK-8150 or placebo was fixed for all Panel D periods). This reporting group presents data for the Panel D participants administered MK-8150. The dose range of MK-8150 administered for Panel D was 50 mg to 200 mg.
Panel D – Placebo Within Panel D, 8 healthy participants were randomly assigned to receive single doses of MK-8150, and 2 were randomly assigned to receive single administrations of matching placebo throughout the up to 5 treatment periods according to a computer-generated allocation schedule (i.e., assignment of a participant to either MK-8150 or placebo was fixed for all Panel D periods). This reporting group presents data for the Panel D participants administered placebo.
Total Total of all reporting groups

Baseline Measures
   Panel A – MK-8150 2 to 90 mg/Placebo   Panel B – MK-8150 4 to 120 mg/Placebo   Panel C – MK-8150 5 to 90 mg/Placebo   Panel D – MK-8150 50 to 200 mg   Panel D – Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 8   8   8   8   2   34 
Age 
[Units: Years]
Mean (Standard Deviation)
 37.5  (9.8)   34.8  (8.0)   51.4  (6.8)   44.1  (6.9)   39.0  (12.7)   42  (10) 
Gender 
[Units: Participants]
           
Female   0   0   0   0   0   0 
Male   8   8   8   8   2   34 
Central Systolic Blood Pressure (cSBP) 
[Units: Mm Hg]
Mean (Standard Deviation)
 98  (7)   98  (6)   125  (8)   102  (9)   105  (6)   106  (13) 
Augmentation Index (AIx) [1] 
[Units: Percentage of central pulse pressure]
Mean (Standard Deviation)
 7  (3)   8  (4)   22  (8)   10  (11)   8  (12)   12  (9) 
[1] 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. AIx is the percentage of the central pulse pressure attributed to the reflected pulse wave, and is an indirect measure of systemic arterial stiffness.
Heart Rate (HR) 
[Units: Beats per minute]
Mean (Standard Deviation)
 58  (7)   54  (5)   67  (9)   61  (7)   45  (1)   59  (9) 
Central Diastolic Blood Pressure (cDBP) 
[Units: Mm Hg]
Mean (Standard Deviation)
 85  (6)   84  (6)   107  (6)   86  (8)   91  (6)   91  (11) 
Peripheral Systolic Blood Pressure (pSBP) 
[Units: Mm Hg]
Mean (Standard Deviation)
 119  (5)   119  (6)   148  (7)   125  (8)   126  (12)   128  (14) 
Peripheral Diastolic Blood Pressure (pDBP) 
[Units: Mm Hg]
Mean (Standard Deviation)
 75  (6)   73  (6)   94  (6)   75  (8)   80  (7)   79  (10) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With an Adverse Event (AE)   [ Time Frame: Up to 14 days after the last dose (Up to approximately 42 days) ]

2.  Primary:   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) ]

3.  Primary:   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 ]

4.  Primary:   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 ]

5.  Primary:   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 ]

6.  Primary:   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 ]

7.  Primary:   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 ]

8.  Primary:   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 ]

9.  Primary:   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 ]

10.  Primary:   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 ]

11.  Primary:   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 ]

12.  Primary:   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 ]

13.  Primary:   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 ]

14.  Primary:   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 ]

15.  Primary:   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 ]

16.  Primary:   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 ]

17.  Primary:   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 ]

18.  Primary:   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 ]

19.  Primary:   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 ]

20.  Primary:   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 ]

21.  Primary:   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 ]

22.  Primary:   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 ]

23.  Primary:   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 ]

24.  Primary:   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 ]

25.  Primary:   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 ]

26.  Primary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications of Results:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01590810     History of Changes
Other Study ID Numbers: 8150-001
2012-001281-15 ( EudraCT Number )
Study First Received: May 1, 2012
Results First Received: March 3, 2016
Last Updated: September 8, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products