Safety, Tolerability and Pharmacokinetics of MK-8266 in Elderly Subjects With High Blood Pressure (MK-8266-003 AM1)

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01263314
First received: November 15, 2010
Last updated: March 25, 2011
Last verified: March 2011
  Purpose

This is a randomized, double-blind, placebo-controlled study. Two panels, each consisting of eight participants (8 elderly males with mild to moderate hypertension in Panel A and 8 elderly females with mild to moderate hypertension in Panel B) will be randomized to receive either MK-8266 or matching placebo in a 3:1 ratio. Participants will receive single doses of MK-8266 or matching placebo in three treatment periods (Periods 1 through 3). In both Panel A and Panel B, doses will escalate in a rising, fixed sequence. In Period 1 (0.3 mg), Period 2 (0.6 mg), and Period 3 (1.0 mg) once daily doses of MK-8266 or matching placebo will be administered. Blood samples will be obtained pre-dose and at selected time points up to 48 hours post-dose for determination of MK-8266 plasma concentrations.


Condition Intervention Phase
Hypertension
Drug: MK-8266
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Single Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MK-8266 in Elderly Subjects With Hypertension

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with adverse events (AEs). [ Time Frame: Baseline to 10-14 days post last dose ] [ Designated as safety issue: Yes ]
  • Change from baseline in laboratory hematology values. [ Time Frame: Baseline to 10-14 days post last dose ] [ Designated as safety issue: Yes ]
  • Change from baseline in laboratory chemistry values. [ Time Frame: Baseline to 10-14 days post last dose ] [ Designated as safety issue: Yes ]
  • Change from baseline in laboratory urinalysis values. [ Time Frame: Baseline to 10-14 days post last dose ] [ Designated as safety issue: Yes ]
  • Change from baseline in systolic blood pressure (SBP). [ Time Frame: Baseline to 10-14 days post last dose ] [ Designated as safety issue: Yes ]
  • Change from baseline in heart rate (HR). [ Time Frame: Baseline to 10-14 days post last dose ] [ Designated as safety issue: Yes ]
  • Change from baseline in ECG. [ Time Frame: Baseline to 10-14 days post last dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Plasma AUC(0-∞) of MK-8266. [ Time Frame: Before dose, and at 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours after dose ] [ Designated as safety issue: No ]
  • Plasma Cmax of MK-8266. [ Time Frame: Before dose, and at 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours after dose ] [ Designated as safety issue: No ]
  • Plasma Tmax of MK-8266. [ Time Frame: Before dose, and at 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours after dose ] [ Designated as safety issue: No ]
  • Apparent terminal half-life of MK-8266. [ Time Frame: Before dose, and at 1.5, 2, 3, 4, 6, 8, 12, 24, 36, and 48 hours after dose ] [ Designated as safety issue: No ]
  • The time weighted average systolic blood pressure (SBP) evaluated over 8 hours post dose (TWA[0-8hrs]) following a single oral dose of MK-8266. [ Time Frame: 8 hours post dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8266,0.3 mg
A single dose of 0.3 mg MK-8266 following an 8 hour overnight fasting period.
Drug: MK-8266
Oral capsules, 0.1 mg potency
Placebo Comparator: Placebo to MK-8266, 0.3 mg
A single dose of Placebo following an 8 hour overnight fasting period.
Drug: Placebo
Oral placebo capsules to match MK-8266 capsules
Experimental: MK-8266, 0.6 mg
A single dose of 0.6 mg MK-8266 following an 8 hour overnight fasting period.
Drug: MK-8266
Oral capsules, 0.1 mg potency
Placebo Comparator: Placebo to MK-8266, 0.6 mg
A single dose of Placebo following an 8 hour overnight fasting period.
Drug: Placebo
Oral placebo capsules to match MK-8266 capsules
Experimental: MK-8266, 1 mg
A single dose of 1 mg MK-8266 following an 8 hour overnight fasting period.
Drug: MK-8266
Oral capsules, 0.1 mg potency
Placebo Comparator: Placebo to MK-8266, 1 mg
A single dose of Placebo following an 8 hour overnight fasting period.
Drug: Placebo
Oral placebo capsules to match MK-8266 capsules

  Eligibility

Ages Eligible for Study:   65 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Participants are male or non-childbearing female.
  • Participant with essential hypertension (HTN), Grade 1 or 2 (as per European Society of Hypertension [ESH]) or isolated mild to moderate systolic HTN. High normal systolic BP ≥130 mmHg will be also allowed. Blood pressures to be confirmed on at least three occasions pre- study. The possibility of secondary causes of HTN should be assessed. Participants who are being treated for HTN with drugs (including beta blocking medications) may be able to participate if the drug doses can be reduced or discontinued, at the discretion of the investigator.
  • Participants with a Body Mass Index (BMI) ≤35 kg/m2 at the screening visit.
  • Participants judged to be generally in good health based on medical history, physical examination, vital sign measurements (with the exception of HTN), and laboratory safety tests done at the screening visit.
  • Participant has no clinically significant abnormality (confirmed by the investigator in consultation with the Merck Clinical Monitor) on electrocardiogram (ECG) or Holter Monitor Evaluation performed at the screening visit and/or prior to administration of the initial dose of study drug.
  • Participants must have a platelet count ≥150,000 cu/mL at the screening and pre-study visit.
  • Participants, at screening, will have a positive Augmentation Index.
  • Participant has been a nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months; participants who have discontinued smoking or the use of nicotine/nicotine containing products for at least 3 months may be enrolled at the discretion of the investigator.
  • Participant is willing to comply with the study restrictions.
  • Participant has a negative test for hidden blood in the stool at screening.

Exclusion criteria:

  • Participants who have had situational depression may be enrolled in the study at the discretion of the investigator.
  • Participant has an estimated creatinine clearance of ≤60 mL/min based on the Cockcroft-Gault equation.
  • Participant has a history of stroke, chronic seizures, or major neurological disorder.
  • Participant has a history of clinically significant endocrine, gastrointestinal, cardiovascular (with the exception of HTN), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases. Participants with a history of uncomplicated kidney stones or childhood asthma may be enrolled in the study at the discretion of the investigator.
  • Patient demonstrates low blood pressure at screening and Pre-dose Day 1 while going from a semi-recumbent to standing position.
  • Participant has a functional disability that can interfere with rising from a semi-recumbent position to the standing position.
  • Participant has any personal or family history of a bleeding or a clotting disorder.
  • Participant has a history of frequent nosebleeds.
  • Participant has a history of cancer with the exceptions of: adequately treated non-melanoma skin carcinoma or carcinoma in situ of the cervix; other malignancies which have been successfully treated >10 years prior to the screening visit, for which in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of the screening visit; or, participants, who, in the opinion of the study investigator, are highly unlikely to sustain a recurrence for the duration of the study.
  • Participant has a history of clinically significant cardiac disease including, but not limited to hemodynamically relevant heart valve disease (if there would be any uncertainty about the diagnosis, confirmation with an echocardiography within 3 months of screening is required), or evidence of secondary cardiac damage.
  • Participant is categorized as a class II or greater functional classification for heart failure according to the New York Heart Association (NYHA).
  • Participant is unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [Hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study until the post-study visit. Certain medication use may be permitted after consultation with the Merck clinical monitor.
  • Participant currently and regularly uses aspirin (including low dose) and cannot be discontinued from it from 2 weeks prior to study start or has used aspirin within 2 weeks prior to study start (and anticipates using it during the course of the study); this applies also to any pain relievers and cold or sinus remedies that have aspirin in them, and the use of anti-platelet drugs, such as clopidogrel or dipyridamole. Chronic use of certain non-steroidal anti-inflammatory drugs (NSAIDs) such as ≥500 mg of naproxen twice a day must be also avoided beginning at least 2 weeks prior the study and until the post-study visit.
  • Participant anticipates using sildenafil (Viagra®), tadalafil (Cialis®), or Vardenafil (Levitra®).
  • Participant uses or anticipates using organic nitrate preparations (for example, nitroglycerin, isosorbide mononitrate, isosorbide dinitrate or pentaerythritol) during the course of the study.
  • Participant consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day. Participants that consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator.
  • Participant consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day.
  • Participant has had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks prior to the screening visit. The 4- week window will be derived from the date of the last study procedure (i.e., post-study, AE follow-up, etc.) in the previous study to the screening visit of the current study.
  • Participant has a history of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food.
  • Participant is currently a regular user of illicit drugs or has a history of drug/alcohol abuse within approximately 1 year of the screening visit.
  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.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier: NCT01263314     History of Changes
Other Study ID Numbers: MK-8266-003
Study First Received: November 15, 2010
Last Updated: March 25, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Merck Sharp & Dohme Corp.:
Hypertension

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 01, 2014