Clinical trial NCT01446003: A Study of the Effect of MK-8457 on Blood Pressure in Hypertensive Participants (MK-8457-004-AM1)
Official title: A Multiple-Dose Clinical Trial to Study the Effect of MK-8457 on Ambulatory Blood Pressure in Hypertensive Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-10-04
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Change From Baseline to Day 10 in 24-hour Mean Ambulatory Systolic Blood Pressure (SBP)
timeFrame: Baseline and Day 10
measure: Number of Participants Who Experienced at Least One Adverse Event (AE)
timeFrame: Up to 70 days
measure: Number of Participants Who Discontinued the Study Medication Due to an AE
timeFrame: Up to 70 days
Secondary outcomes:
measure: Change From Baseline to Day 10 in 24-hour Mean Ambulatory Diastolic Blood Pressure (DBP)
timeFrame: Baseline and Day 10
measure: Change From Baseline to Day 10 in Maximum Moving Average (maxMAΔ) Blood Pressure Measured Over 4 Hours
timeFrame: Up to 4 hours postdose on Days 1 and 10
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12hr) of MK-8457
timeFrame: 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
measure: Maximum Concentration (Cmax) of MK-8457
timeFrame: 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
measure: Time to Maximum Concentration (Tmax) of MK-8457
timeFrame: 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
measure: Trough Plasma Concentration (Ctrough) of MK-8457
timeFrame: 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
Other outcomes:
Locations:
city: Miramar
country: United States
facility: Call for Information
state: Florida
city: Tacoma
country: United States
facility: Call for Information
state: Washington
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: