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: February 26, 2014
Last verified: February 2014
  Purpose

This study will evaluate the safety and tolerability of MK-8150 and its effect on central systolic blood pressure (cSBP) and heart rate corrected augmentation index (AIx) when given as single oral doses in healthy males and in males with mild-to-moderate hypertension.


Condition Intervention Phase
Hypertension
Isolated Systolic Hypertension (ISH)
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
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Single Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately 20 weeks ] [ Designated as safety issue: Yes ]
  • Number of Participants who Discontinue due to AEs [ Time Frame: Approximately 20 weeks ] [ Designated as safety issue: Yes ]
  • Time-weighted Average Across 24 hours (TWA0-24hrs) for Central Systolic Blood Pressure (cSBP) [ Time Frame: Predose to 24 hours Postdose (for each Dosing Period of Each Panel) ] [ Designated as safety issue: No ]
  • TWA0-24hr of Augmentation Index (AIx) [ Time Frame: Predose to 24 hours Postdose (for each Dosing Period of Each Panel) ] [ Designated as safety issue: No ]
  • Mean Time Weighted Average over 12 hours (TWA0-12hr) for Heart Rate (HR) [ Time Frame: Predose up to 12 hours postdose of each period ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: May 2012
Study Completion Date: February 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel A-Healthy
Within each of the 5 treatment periods, 6 participants will be randomly assigned to receive MK-8150, and 2 will be randomly assigned to receive matching placebo according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel A will be 2.0 mg to 90 mg.
Drug: MK-8150 2.0 mg
Single oral 2.0-mg dose of MK-8150
Drug: MK-8150 10 mg
Single oral 10-mg dose of MK-8150
Drug: MK-8150 40 mg
Single oral 40-mg dose of MK-8150 without food (fasted) and with food (fed)
Drug: MK-8150 90 mg
Single oral 90-mg dose of MK-8150
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Experimental: Panel B-Healthy
Within each of the 5 treatment periods, 6 participants will be randomly assigned to receive MK-8150, and 2 will be randomly assigned to receive matching placebo according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel B will be 5.0 mg to 160 mg.
Drug: MK-8150 5.0 mg
Single oral 5.0-mg dose of MK-8150
Drug: MK-8150 20 mg
Single oral 20-mg dose of MK-8150
Drug: MK-8150 60 mg
Single oral 60-mg dose of MK-8150
Drug: MK-8150 120 mg
Single oral 120-mg dose of MK-8150
Drug: MK-8150 160 mg
Single oral 160-mg dose of MK-8150
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Experimental: Panel C-Mild/Moderate Hypertension
Within each of the 5 treatment periods, 6 participants will be randomly assigned to receive MK-8150, and 2 will be randomly assigned to receive matching placebo according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel C will be 160 mg to 1200 mg.
Drug: MK-8150 160 mg
Single oral 160-mg dose of MK-8150
Drug: MK-8150 320 mg
Single oral 320-mg dose of MK-8150
Drug: MK-8150 600 mg
Single oral 600-mg dose of MK-8150
Drug: MK-8150 900 mg
Single oral 900-mg dose of MK-8150
Drug: MK-8150 1200 mg
Single oral 1200-mg dose of MK-8150
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Experimental: Panel D-Healthy
Within each panel, 8 subjects will be randomly assigned to MK-8150 and 2 subjects will be randomly assigned to placebo throughout the 5 periods according to a computer-generated allocation schedule. The dose range of MK-8150 for Panel D will be 50 mg to 500 mg.
Drug: Placebo for MK-8150
Single oral dose-matched dose of Placebo for MK-8150
Drug: MK-8150 50 mg
Single oral 50-mg dose of MK-8150
Drug: MK-8150 100 mg
Single oral 100-mg dose of MK-8150
Drug: MK-8150 200 mg
Single oral 200-mg dose of MK-8150
Drug: MK-8150 400 mg
Single oral 400-mg dose of MK-8150
Drug: MK-8150 500 mg
Single oral 500-mg dose of MK-8150

Detailed Description:

Up to three planned panels (A, B and C) of either 8 healthy participants or 8 participants with mild to moderate hypertension will be enrolled. For Panel A and Panel B, dosing will occur in an alternating fashion between Panel A and Panel B with dosing commencing in Panel A. Participants will receive alternating single rising oral doses of MK-8150 or placebo in up to 5 treatment periods (Periods 1 through 5). Subsequent doses in any Panel will be administered only after careful evaluation of safety, tolerability, and pharmacodynamic effects of a given dose. For Panel C, participants will receive single rising oral doses of MK-8150 or placebo in up to 5 treatment periods (Periods 1 through 5). Depending on safety, tolerability and hemodynamic effects observed in the healthy participants, Panels A and/or B may be truncated and dosing may proceed in Panel C with hypertensive participants. In this case, dosing of hypertensive participants in Panel C will start with the second highest dose achieved in healthy participants.

Amendment 1 of the protocol added Panel D (healthy males) based on the pharmacokinetic, pharmacodynamic and safety results from Panels A-C. Participants in Panel D will receive alternating single rising oral doses of MK-8150 or placebo in up to 5 treatment periods (Periods 1 through 5) at a dose range of 50 mg to 500 mg of MK-8150. Each treatment period will be approximately 3-4 days apart.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Between 18 and 50 years of age for Panels A, B and D, or between 18 and 60 years of age (inclusive) for Panel C.
  • Systolic blood pressure (SBP) > 110 and ≤ 140 mmHg for Panels A, B, and D or 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

Exclusion Criteria:

  • 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 neoplastic disease (cancer)
  • 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
  • Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
  • History of significant multiple and/or severe allergies (including latex allergy)
  • Regular user (including recreational user) of illicit drugs or has a history of drug (including alcohol) abuse within approximately 1 year
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01590810     History of Changes
Other Study ID Numbers: 8150-001, 2012-001281-15
Study First Received: May 1, 2012
Last Updated: February 26, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 19, 2014