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

May 1, 2012
February 26, 2014
May 2012
January 2013   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01590810 on ClinicalTrials.gov Archive Site
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A Single Rising Dose Study of MK-8150 (MK-8150-001)
A Single Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Hypertension
  • Isolated Systolic Hypertension (ISH)
  • 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: 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: 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
  • 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
  • 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.
    Interventions:
    • Drug: MK-8150 2.0 mg
    • Drug: MK-8150 10 mg
    • Drug: MK-8150 40 mg
    • Drug: MK-8150 90 mg
    • Drug: 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.
    Interventions:
    • 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: 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.
    Interventions:
    • 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
  • 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.
    Interventions:
    • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
34
February 2013
January 2013   (final data collection date for primary outcome measure)

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
Male
18 Years to 60 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01590810
8150-001, 2012-001281-15
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP