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A Study of the Effect of MK-8457 on Blood Pressure in Hypertensive Participants (MK-8457-004-AM1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01446003
First received: September 30, 2011
Last updated: June 1, 2017
Last verified: May 2017
  Purpose
This study will evaluate the effect of treatment with multiple doses of MK-8457 on systolic blood pressure in participants with mild to moderate hypertension in addition to safety and tolerability. The study hypothesis is that MK-8457 does not increase systolic blood pressure to a clinically significant extent, as measured by 24-hour mean ambulatory systolic blood pressure change from baseline after 10 days of dosing.

Condition Intervention Phase
Hypertension Drug: MK-8457 Drug: Placebo for MK-8457 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multiple-Dose Clinical Trial to Study the Effect of MK-8457 on Ambulatory Blood Pressure in Hypertensive Patients

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

Primary Outcome Measures:
  • Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP) [ Time Frame: Baseline and Day 10 ]
    SBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour least squares (LS) mean ambulatory SBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour SBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.

  • Number of Participants Who Experienced at Least One Adverse Event (AE) [ Time Frame: Up to 70 days ]
    An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.

  • Number of Participants Who Discontinued the Study Medication Due to an AE [ Time Frame: Up to 70 days ]
    An AE is defined as any unfavorable and unintended medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.


Secondary Outcome Measures:
  • Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP) [ Time Frame: Baseline and Day 10 ]
    DBP was measured using ambulatory blood pressure monitoring (ABPM) on Day -1 and Day 10 of each treatment period. The 24-hour LS mean ambulatory DBP change from baseline was then determined for Day 10, the last day of multiple dose treatment. Baseline is defined as the average 24-hour DBP for each participant on Day -1. Increased values represent an increase in hypertensive severity.

  • Change From Baseline to Day 10 in Maximum Moving Average (maxMAΔ) Blood Pressure Measured Over 4 Hours [ Time Frame: Up to 4 hours postdose on Days 1 and 10 ]
    The effect of drug on resting blood pressure was estimated using maxMAΔ. The maxMAΔ in blood pressure was calculated as the maximum moving average change from baseline to Day 10 of 3 consecutive 15-minute blood pressure measurements across the first 4 hours after the morning (AM) and evening (PM) doses. In this method, the LS means of three consecutive time points over the 4 hour period were determined and the maximum LS mean was used for the endpoint. Blood pressure was determined using continuous monitoring at rest. Increased values represent an increase in hypertensive severity.

  • Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12hr) of MK-8457 [ Time Frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10 ]
    AUC0-12hr is an estimate of total plasma exposure to study drug over the dosing interval (12hr). Plasma concentrations of MK-8457 were determined on Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group is not included; this endpoint evaluated only the MK-8457 group.

  • Maximum Concentration (Cmax) of MK-8457 [ Time Frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10 ]
    Maximum plasma concentrations of MK-8521 were determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.

  • Time to Maximum Concentration (Tmax) of MK-8457 [ Time Frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; 24 hrs post-AM dose on Day 10 ]
    Tmax was determined for the AM dose on Day 1 and Day 10. The placebo group was not included; this endpoint evaluated only the MK-8457 group.

  • Trough Plasma Concentration (Ctrough) of MK-8457 [ Time Frame: pre-AM dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post AM dose on Days 1 and 10; pre-AM dose on Day 5 or 6 ]
    The lowest plasma concentration reached by the drug prior to the next administration was determined for Day 1 (after initial dosing) and Day 10 (after multiple dosing). The placebo group was not included; this endpoint evaluated only the MK-8457 group.


Enrollment: 31
Actual Study Start Date: October 25, 2011
Study Completion Date: March 3, 2012
Primary Completion Date: February 18, 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8457-Placebo Sequence
Participants received MK-8457 100 mg twice daily (BID) for 10 days followed by Placebo for 10 days. Each treatment was separated by a 10-day washout.
Drug: MK-8457
10 x 10-mg capsule BID for 10 days
Drug: Placebo for MK-8457
10 x 10-mg capsule BID for 10 days
Experimental: Placebo-MK-8457 Sequence
Participants received Placebo for 10 days followed by MK-8457 100 mg BID for 10 days. Each treatment was separated by a 10-day washout.
Drug: MK-8457
10 x 10-mg capsule BID for 10 days
Drug: Placebo for MK-8457
10 x 10-mg capsule BID for 10 days

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • If female, must be of non-childbearing potential
  • If male with female partner(s) of child-bearing potential must agree to use a medically acceptable method of contraception during the study and for 90 days after the last dose of study drug
  • Body mass index (BMI) ≤35 kg/m^2
  • Mild-to-moderate hypertension requiring treatment with one or more antihypertensive agents
  • Receiving stable treatment for hypertension for at least 8 weeks prior to the start of dosing and continuing therapy for duration of study
  • No clinically significant arrhythmias or clinically significant abnormality on electrocardiogram
  • Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Exclusion Criteria:

  • Any illness that might confound the results of the study or poses an additional risk
  • History of stroke, chronic seizures, or major neurological disorder
  • Clinically significant endocrine, gastrointestinal, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
  • Clinically significant cardiovascular disease or has active angina
  • History of malignant neoplastic disease
  • Taking 325 mg aspirin daily
  • Taking 3 or more medications for the treatment of hypertension
  • Unable to refrain from or anticipates the use of any non-steroidal anti-inflammatory drugs (NSAIDs)
  • Consumes excessive amounts of alcohol and/or coffee, tea, cola, or other caffeinated beverages
  • Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
  • Significant multiple and/or severe allergies
  • Regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446003

Locations
United States, Florida
Call for Information
Miramar, Florida, United States
United States, Washington
Call for Information
Tacoma, Washington, United States
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01446003     History of Changes
Other Study ID Numbers: 8457-004
Study First Received: September 30, 2011
Results First Received: March 20, 2017
Last Updated: June 1, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

ClinicalTrials.gov processed this record on September 21, 2017