Clinical trial NCT01244035: Safety, Pharmacodynamics, and Pharmacokinetics of Different Dosing Regimens of MK-8266 in Participants With Hypertension (MK-8266-008)
Official title: Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics Following Different Dosing Regimens of MK-8266 or Placebo in Subjects With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension
Keywords: High blood pressure
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-11-19
Enrollment: 31
Sex: MALE
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This was designed as a two part study comprising sequential double-dummy, placebo controlled 3-period randomized crossover studies. The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of different doses and dose regimens of MK-8266. Only Part I of the study was completed.


Eligibility criteria: Inclusion Criteria:

* Participant has essential hypertension who is in grade 1 or 2 hypertension according to the European Society of Hypertension (ESH) as delineated in the European Society of Cardiology (ESC) 2007 guidelines, i.e. systolic blood pressure values of 140-179 and diastolic blood pressure values of 90-109 on at least 3 occasions prior to the study.
* Otherwise healthy participants with grade 1 or 2 arterial hypertension who are treated with a single antihypertensive drug and meet the above blood pressure criteria may be enrolled at the discretion of the investigator
* Participant is generally in good health with the exception of hypertension
* Participant is a nonsmoker and/or has not used nicotine or nicotine-containing products for 6 months

Exclusion Criteria:

* Participant has a history of any illness that might confound the results of the study or pose and additional risk to the participant if they take part in the study
* Participant has a history of stroke, chronic seizures, or major neurological disorder
* Participant has a disability that can interfere with rising from a semi-recumbent position to the standing position
* Participant has a personal or family history of a bleeding or clotting disorder
* Participant has a history of frequent nosebleeds or recurrent or active gingivitis
* Participant has a history of cancer, except 1) certain skin cancers; 2) cancer successfully treated more than 10 years prior to the study that has not recurred; or, 3) participants who are unlikely to have a recurrence during the study
* Participant has a history of cardiac disease including but not limited to heart valve disease or evidence of secondary cardiac damage
* Participant is categorized as class II or greater according to the New York Heart Association (NYHA) functional classification for heart failure
* Participant is unable to refrain from use of prescription or non-prescription drugs or herbal remedies (such as St. John's Wort) during the study
* Participant anticipates using phosphodiesterase (PDE5) inhibitors \[sildenafil (Viagra®), tadalafil (Cialis®), or vardenafil (Levitra®)\] during the study
* Participant consumes excessive amounts of alcohol (more than 3 drinks per day) or caffeine (more than 6 servings a day)
* Participant has had major surgery, donated or lost 1 unit of blood, or participated in another investigational within 4 weeks prior to the study
* Participant has a history of multiple and/or severe allergies, or has had an anaphylactic reaction or intolerance to any drugs or food

Primary outcomes:
measure: Adverse Events (AEs)
timeFrame: MK-8266 1.3 mg BID and 0.9 mg FDD groups: Up to Day 4 in each period; MK-8266 1 mg QD group: the last AE was reported on day 10 after the last dose; Placebo group: Up to 10-14 days after the last dose of placebo
measure: Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Days 1 and 3
timeFrame: Pre-dose and 0.5, 1, 2, 4, and 8 hours after dosing on Day 1, and pre-dose and 4 and 8 hours after dosing on Day 3 of each period
measure: Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Day 4
timeFrame: Predose and 2, 4, and 8 hours after dosing on Day 4 of each period
measure: Maximum Plasma Concentration (Cmax) of MK-8266 on Day 1 and Day 3
timeFrame: Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3
measure: Maximum Plasma Concentration (Cmax) of MK-8266 on Day 4
timeFrame: Predose and 2, 4, and 8 hours after dosing on Day 4 of each period
measure: Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 1 and Day 3
timeFrame: Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3
measure: Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 4
timeFrame: Predose and 2, 4, and 8 hours after dosing on Day 4 of each period
measure: Change From Baseline in Heart Rate (HR)
timeFrame: Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3
measure: Change From Baseline in Diastolic Blood Pressure (DBP)
timeFrame: Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: