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

NCT01446003 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 8457-004
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (3)

• Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP)

  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.

  Baseline and Day 10

• Number of Participants Who Experienced at Least One Adverse Event (AE)

  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.

  Up to 70 days

• Number of Participants Who Discontinued the Study Medication Due to an AE

  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.

  Up to 70 days

Secondary Outcomes (6)

• Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP)

  Baseline and Day 10

• Change From Baseline to Day 10 in Maximum Moving Average (maxMAΔ) Blood Pressure Measured Over 4 Hours

  Up to 4 hours postdose on Days 1 and 10

• Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12hr) of MK-8457

  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

• Maximum Concentration (Cmax) of MK-8457

  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

• Time to Maximum Concentration (Tmax) of MK-8457

  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

Study Arms (2)

MK-8457-Placebo Sequence

EXPERIMENTAL

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; Drug: Placebo for MK-8457

Placebo-MK-8457 Sequence

EXPERIMENTAL

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; Drug: Placebo for MK-8457

Interventions

MK-8457 DRUG

10 x 10-mg capsule BID for 10 days

MK-8457-Placebo Sequence; Placebo-MK-8457 Sequence

Placebo for MK-8457 DRUG

10 x 10-mg capsule BID for 10 days

MK-8457-Placebo Sequence; Placebo-MK-8457 Sequence

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (2)

Call for Information

Miramar, Florida, United States

Location

Call for Information

Tacoma, Washington, United States

Location

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2011
• First Posted: October 4, 2011
• Study Start: October 25, 2011
• Primary Completion: February 18, 2012
• Study Completion: March 3, 2012
• Last Updated: February 5, 2019
• Results First Posted: May 2, 2017

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share

Locations

US (2)