A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8150 (MK-8150-002)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01656408
First received: July 12, 2012
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

This study will evaluate the safety and tolerability of MK-8150 after multiple, rising oral dose administration in healthy male participants, male participants with mild to moderate hypertension and elderly participants with mild to moderate hypertension.


Condition Intervention Phase
Hypertension
Isolated Systolic Hypertension
Drug: MK-8150
Drug: Placebo for MK-8150
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 Multiple 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 who Report an Adverse Event [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinued per Panel due to Meeting Hemodynamic Stopping Rules [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • 24-hour Time-weighted Average (TWA0-24hr) Change from Baseline in Central Systolic Blood Pressure (cSBP) [ Time Frame: Panels A-F and H: Predose, Day 1 (up to 24 hours postdose) and Day 10 (up to 24 hours postdose) and Panels G and I-J: Predose, Day 1 (up to 24 hours postdose) and Days 8, 15, 22, and 28 (up to 24 hours postdose) ] [ Designated as safety issue: No ]
  • 24-hour Weighted Average Change from Baseline in Heart Rate (HR TWA0-24hrs) [ Time Frame: Panels A-F and H: Predose, Day 1 (up to 24 hours postdose) and Day 10 (up to 24 hours postdose) and Panels G and I-J: Predose, Day 1 (up to 24 hours postdose) and Days 8, 15, 22, and 28 (up to 24 hours postdose) ] [ Designated as safety issue: No ]
  • Area Under the Concentration Time-curve from Hour 0 to τ (where τ indicates the interval between doses [AUC(0-τ)]) of MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration (Cmax) of MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]
  • Time to Cmax (Tmax) for MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]
  • Apparent Terminal Half-life (t1/2) for MK-8150 [ Time Frame: Panels A-D and H- Day 1 and Day 10; Panels E-F- Day 1, Day 6 and Day 15; Panels G, I-J - Days 1, 8, 15, 22, and 28 ] [ Designated as safety issue: No ]

Enrollment: 103
Study Start Date: August 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panel A: Mild/Moderate Hypertension
MK-8150 or matching placebo once daily, capsules, oral, for 10 days
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel B: Mild/Moderate Hypertension
MK-8150 or matching placebo once daily, capsules, oral, for 10 days
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel C: Mild/Moderate Hypertension
MK-8150 or matching placebo once daily, capsules, oral, for 10 days
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel D: Mild/Moderate Hypertension
MK-8150 or matching placebo once daily, capsules, oral, for 10 days
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel E-Elderly
Single dose of MK-8150 or placebo on Study Day 1 followed by a wash-out of at least 5 days, then MK-8150 or placebo once daily at a lower dose for 10 days
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel F - Elderly
Single dose of MK-8150 or placebo on Study Day 1 followed by a wash-out of at least 5 days, then MK-8150 or placebo once daily at a lower dose for 10 days
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel G - Healthy - Dose Titration
MK-8150 or matching placebo will be administered once daily for 28 days. Dose may be adjusted on Day 8, Day 15, and Day 22.
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel H - Crossover
MK-8150 or matching placebo for 10 consecutive days in 2-period crossover with minimum 3 weeks washout period between the 2 treatment periods
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel I - Dose Titration
MK-8150 or matching placebo will be administered once daily for 28 days. Dose may be adjusted on Day 8, Day 15, and Day 22.
Drug: MK-8150 Drug: Placebo for MK-8150
Experimental: Panel J - Dose Titration
MK-8150 or matching placebo will be administered once daily for 28 days. Dose may be adjusted on Day 8, Day 15, and Day 22.
Drug: MK-8150 Drug: Placebo for MK-8150

Detailed Description:

Ten panels (Panels A-J), consisting of 104 participants in total, will be randomized to receive either MK-8150 or matching placebo.

Males (18 to 55 years of age, inclusive) with mild to moderate hypertension will be randomized in Panels A-D and will receive either MK-8150 or placebo as once daily treatment for 10 consecutive days.

Elderly males and females (65 to 80 years of age, inclusive) with mild to moderate hypertension will be included in Panels E and F and will receive a single dose of either MK-8150 or placebo on Study Day 1 followed by at least 5 days of wash-out before proceeding to once daily treatment of the same randomized treatment at a lower dose for 10 consecutive days.

Participants 18 to 65 years of age with resistant hypertension will be enrolled in Panels H and will receive in randomized sequences of MK-8150/placebo or placebo/MK-8150 in 2 treatment periods. There will be a minimum 3 weeks washout period between the 2 treatment periods in Panel H.

Healthy males (18 to 55 years of age, inclusive) will be enrolled in Panel G and will receive MK-8150 or matching placebo once daily for 28 days. Participants randomized to MK-8150 in Panel G who meet all of the dose-escalation criteria and have not met any of the hemodynamic stopping criteria will be eligible for dose increases on Day 8, Day 15, and Day 22. If dose escalation criteria are not met (or if the Investigator or Sponsor elects not to increase the dose), then the participant will continue on the current dose and will be eligible for a dose increase at the next dose-escalation decision day if all dose-escalation criteria are met at that time.

Male participants (18 to 65 years of age, inclusive) with mild to moderate hypertension will be randomized in Panels I and J. In each panel, 18 participants will receive either MK-8150 or matching placebo as once daily treatment for up to 28 consecutive days. Participants who are randomized to placebo will receive placebo throughout the study. On Days 8, 15 and 22 in both Panels I and J, participants will be eligible for dose-escalation, down-dosing, or continuing their current dose depending on their hemodynamic status. Participants in Panels I and J who meet down-dosing criteria at any time during the study will have their doses reduced to the previous well-tolerated

dose level until the next dose-escalation decision day, or through the end of the study, whichever is first.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Hypertensive male participant between 18 to 55 years of age for Panels A to D; hypertensive male or female of non-childbearing potential between 65 to 80 years of age for Panels E and F; healthy males between 18 to 55 years of age for Panel G; hypertensive male or non-childbearing potential female between 18 to 65 years of age (inclusive) for Panel H; hypertensive male between 18 to 65 years of age for Panels I and J
  • Body Mass Index (BMI) ≤ 33 kg/m^2
  • In good age appropriate health
  • No history of clinically significant cardiac disease
  • Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months

Exclusion Criteria:

  • Mentally or legally incapacitated, has significant emotional problems or has a history of a clinically significant psychiatric disorder over the last 5 years
  • History of stroke, chronic seizures, or a relevant major neurological disorder
  • History of neoplastic disease (cancer)
  • Unable to refrain from or anticipates the use of any medication, including any non-steroidal anti-inflammatory drug (NSAID) and aspirin-containing products, prescription and non-prescription drugs or herbal remedies for 2 weeks prior to study start up to end of study
  • Anticipates using erectile dysfunction medications during the study
  • Uses or anticipates using organic nitrates during the course of the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)
  • Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) 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)
  • Current regular user (including ) of any 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: NCT01656408     History of Changes
Other Study ID Numbers: 8150-002, 2012-002596-34
Study First Received: July 12, 2012
Last Updated: September 6, 2013
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 July 22, 2014