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Completed

NCT Number: NCT01244035

Safety, Pharmacodynamics, and Pharmacokinetics of Different Dosing Regimens of MK-8266 in Participants With Hypertension (MK-8266-008)

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.

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Key information

Conditions

Hypertension Cardiovascular Diseases Vascular Diseases

Age range

21 year–60 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Treatment A

Drug

MK-8266 1.3 mg orally twice daily (BID, 1 mg in the morning and 0.3 mg 8 hours later) plus placebo to match Treatment B on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Other names: MK-8266 1.3 mg BID

Treatment B

Drug

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, total dose of 0.9 mg) plus placebo to match Treatment A on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Other names: MK-8266 0.9 mg FDD

Treatment C

Drug

Placebo to match MK-8266 Treatments A and B orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Other names: Placebo

Treatment D

Drug

MK-8266 orally twice daily (1 mg in the morning and 0.4 mg 8 hours later) plus placebo to match Treatment E on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment E

Drug

MK-8266 0.2 mg orally every 2 hours (total dose of 1.4 mg) plus placebo to match Treatment D on Days 1 through 3. On Day 4, single dose of 1 mg MK-8266.

Treatment F

Drug

Placebo to match MK-8266 Treatments D and E orally daily on Days 1 through 3. On Day 4, single dose of placebo to match MK-8266.

Primary outcomes

  1. Adverse Events (AEs)

    Time frame: 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

    The number of participants with one or more clinical or laboratory AEs was assessed. 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.

  2. Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Days 1 and 3

    Time frame: 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

    The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided.

  3. Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Day 4

    Time frame: Predose and 2, 4, and 8 hours after dosing on Day 4 of each period

    The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided.

  4. Maximum Plasma Concentration (Cmax) of MK-8266 on Day 1 and Day 3

    Time frame: Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3

    The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided.

  5. Maximum Plasma Concentration (Cmax) of MK-8266 on Day 4

    Time frame: Predose and 2, 4, and 8 hours after dosing on Day 4 of each period

    The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided.

  6. Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 1 and Day 3

    Time frame: Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3

    The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 1 and Day 3.

  7. Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 4

    Time frame: Predose and 2, 4, and 8 hours after dosing on Day 4 of each period

    The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 4.

  8. Change From Baseline in Heart Rate (HR)

    Time frame: Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3

    The effect of MK-8266 and placebo on changes in HR were assessed, as measured by time weighted average change from baseline in HR over 0-24 hours postdose (TWA^0-24 hr) on Day 3. Baseline values for HR are shown in the Baseline Characteristics section.

  9. Change From Baseline in Diastolic Blood Pressure (DBP)

    Time frame: Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3

    The effect of MK-8266 and placebo on changes in diastolic blood pressure (DBP) were assessed, as measured by time weighted average change from baseline in DBP over 0-24 hours postdose (TWA^0-24 hr) on Day 3. Baseline values for DBP are shown in the Baseline Characteristics section.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2010
Primary completion
2010
Study completion
2010
First posted
Nov 19, 2010
Registry last updated
Feb 28, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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