A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK8266 in Hypertensive Men (MK-8266-002)
A Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-8266
2 other identifiers
interventional
40
0 countries
N/A
Brief Summary
This study evaluated adverse events (AEs), study discontinuation due to AEs, and pharmacodynamics of MK-8266 in male participants with mild to moderate hypertension.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 hypertension
Started Mar 2010
Typical duration for phase_1 hypertension
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2010
CompletedFirst Submitted
Initial submission to the registry
March 26, 2010
CompletedFirst Posted
Study publicly available on registry
March 30, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2010
CompletedResults Posted
Study results publicly available
August 12, 2019
CompletedAugust 12, 2019
June 1, 2019
8 months
March 26, 2010
February 21, 2018
June 24, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Participants Receiving MK-8266 or Placebo Who Experienced At Least One Adverse Event (AE) During Treatment and Postdose Follow-up
Assessment of the number of participants with at least one clinical or laboratory AE in those receiving multiple oral doses of MK-8266. 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 sponsor's product, whether or not considered related to the use of the product.
Up to 24 days
Participants Receiving MK-8266 or Placebo Who Discontinued Treatment Due to an AE
Assessment of the number of participants receiving MK-8266 who discontinued therapy due to an AE over 10 days of treatment. 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 SPONSOR's product, whether or not considered related to the use of the product. The number of participants in any treatment group who discontinued therapy due to an AE was primarily assessed for Days 0-10.
Up to 10 days
Change From Baseline in Systolic Blood Pressure (SBP) Following Multiple Oral Doses of MK-8266 or Placebo
Assessment of the change from baseline in SBP, obtained using a validated, semi-automated oscillometric device. Evaluated for MK-8266 relative to placebo in participants, as measured by the time weighted average change over 24 hours postdose (TWA\^0-24hrs) on dosing Day 10. Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this analysis.
Baseline and Day 10
Heart Rate (HR) on Day 10 Following Multiple Oral Doses of MK-8266 or Placebo
Assessment of HR (beats/min) on Day 10 (24-hours postdose) with MK-8266 relative to placebo in participants, as measured by the time weighted average change over 24 hours postdose (TWA\^0-24hrs). Panel D and Panel E had identical treatments (MK-8266 0.8 mg TID), which were combined for this analysis. Baseline HR values are shown in the Baseline Characteristics section for Panels A, B, C, D, E.
Day 10 (24 hours postdose)
Secondary Outcomes (4)
Aortic Augmentation Index (AIx) on Day 10 Following Multiple Oral Doses of MK-8266 or Placebo
Day 10
Change From Baseline in Cyclic Guanosine Monophosphate (cGMP) Following Multiple Oral Doses of MK-8266 or Placebo
Baseline and Day 10
Percent Inhibition of Platelet Aggregation Induced by Adenosine Diphosphate (ADP) Following Multiple Oral Doses of MK-8266 or Placebo
Baseline and Day 10 (5 hours postdose)
Percent Inhibition of Platelet Aggregation Induced by Collagen Following Multiple Oral Doses of MK-8266 or Placebo
Baseline and Day 10 (5 hours postdose)
Study Arms (5)
Panel A: MK-8266 BID, 1 mg/Placebo
EXPERIMENTALMK-8266 1 mg (0.7 mg in the morning \[AM\] + 0.3 mg in the evening \[PM\]), or as matching placebo BID.
Panel B: MK-8266 BID, 1.8 mg/Placebo
EXPERIMENTALMK-8266 1.8 mg (1 mg in the AM + 0.8 mg in the PM), or as matching placebo BID.
Panel C: MK-8266 TID, 1.8 mg/Placebo
EXPERIMENTALMK-8266 TID, 1.8 mg (0.6 mg every 6 hours \[q6hr\]), or as matching placebo TID.
Panel D: MK-8266 TID, 2.4 mg/Placebo
EXPERIMENTALMK-8266 TID (Panel D), 2.4 mg (0.8 mg q6hr), or as matching placebo TID. Panel D was completed prior to initiation of Panel E.
Panel E: MK-8266 TID, 2.4 mg/Placebo
EXPERIMENTALMK-8266 TID (Panel E), 2.4 mg (0.8 mg q6hr), or as matching placebo TID. Panel E was initiated after completion of Panel D.
Interventions
MK-8266 1 mg administered as oral capsules (0.7 mg + 0.3 mg), BID for 10 consecutive days. Panel A was completed prior to initiation of Panel B.
MK-8266 1.8 mg administered as oral capsules (1 mg + 0.8 mg), BID for 10 consecutive days. Panel B was completed prior to initiation of Panel C.
MK-8266 1.8 mg administered as oral capsules (0.6 mg), TID for 10 consecutive days. Panel C was completed prior to initiation of Panel D.
MK-8266 TID (Panel D), 2.4 mg administered as oral capsules (0.8 mg), TID for 10 consecutive days. Panel D was completed prior to initiation of Panel E.
Placebo administered as oral capsules BID for 10 consecutive days. Panel A was completed prior to initiation of Panel B.
Placebo administered as oral capsules BID for 10 consecutive days. Panel B was completed prior to initiation of Panel C.
Placebo administered as oral capsules TID for 10 consecutive days. Panel C was completed prior to initiation of Panel D.
Placebo administered as oral capsules TID for 10 consecutive days. Panel D was completed prior to initiation of Panel E.
Placebo administered as oral capsules TID for 10 consecutive days. Panel E was initiated after completion of Panel D.
Eligibility Criteria
You may qualify if:
- Participant is male with essential hypertension (high blood pressure)
- Participant is in good general health (with the exception of hypertension)
- Participant has a Body Mass Index (BMI) \<= 33 kg/m\^2 at the Screening visit
- Participant has a platelet count \>= 150,000 cu/mL at the Screening visit
- Participant has a positive AIx at the Screening visit
You may not qualify if:
- Participant has a history of stroke, chronic seizure, or major neurological disease
- Participant has a functional disability that can interfere with rising from a seated position to the standing position
- Participant has any history of a bleeding or clotting disorder
- Participant has a history of cancer
- Participant is unable to refrain from or anticipates the use of any prescription or non-prescription medication
- Participant consumes excessive amounts of alcohol or caffeinated beverages daily
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 26, 2010
First Posted
March 30, 2010
Study Start
March 1, 2010
Primary Completion
November 1, 2010
Study Completion
November 1, 2010
Last Updated
August 12, 2019
Results First Posted
August 12, 2019
Record last verified: 2019-06
Data Sharing
- IPD Sharing
- Will share
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf