A Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Different Dosing Regimens of MK-8266 in Participants With Hypertension (MK-8266-008 AM1)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01244035
First received: November 17, 2010
Last updated: March 14, 2011
Last verified: March 2011
  Purpose

This is 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.


Condition Intervention Phase
Hypertension
Drug: Treatment A
Drug: Treatment B
Drug: Treatment C
Drug: Treatment D
Drug: Treatment E
Drug: Treatment F
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of participants with adverse experiences [ Time Frame: From day of enrollment to 10-14 days following the last dose of study drug ] [ Designated as safety issue: Yes ]
  • Area under the MK-8266 concentration versus time curve [AUC(0-τ)] [ Time Frame: Four days (Predose Day 1 of each study period through eight hours postdose on Day 4) ] [ Designated as safety issue: No ]
  • Maximum plasma concentration of MK-8266 (Cmax) [ Time Frame: Four days (Predose Day 1 of each study period through eight hours postdose on Day 4) ] [ Designated as safety issue: No ]
  • Time to maximum plasma concentration of MK-8266 (Tmax) [ Time Frame: Four days (Predose Day 1 of each study period through eight hours postdose on Day 4) ] [ Designated as safety issue: No ]
  • Apparent terminal half-life of MK-8266 (t½) [ Time Frame: Four days (Predose Day 1 of each study period through eight hours postdose on Day 4) ] [ Designated as safety issue: No ]
  • Time-weighted average change from baseline in heart rate [ Time Frame: Baseline and average over 0-24 hours postdose on Day 3 ] [ Designated as safety issue: No ]
  • Time-weighted average change from baseline in diastolic blood pressure [ Time Frame: Baseline and average over 0-24 hours postdose on Day 3 ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: August 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I - Sequence ABC
Treatment A in Period 1, Treatment B in Period 2, and Treatment C in Period 3
Drug: Treatment A
MK-8266 orally twice daily (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.
Drug: Treatment B
MK-8266 0.1 mg orally every 2 hours (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.
Drug: Treatment C
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.
Experimental: Part I - Sequence ACB
Treatment A in Period 1, Treatment C in Period 2, and Treatment B in Period 3
Drug: Treatment A
MK-8266 orally twice daily (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.
Drug: Treatment B
MK-8266 0.1 mg orally every 2 hours (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.
Drug: Treatment C
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.
Experimental: Part I - Sequence BCA
Treatment B in Period 1, Treatment C in Period 2, and Treatment A in Period 3
Drug: Treatment A
MK-8266 orally twice daily (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.
Drug: Treatment B
MK-8266 0.1 mg orally every 2 hours (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.
Drug: Treatment C
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.
Experimental: Part I - Sequence BAC
Treatment B in Period 1, Treatment A in Period 2, and Treatment C in Period 3
Drug: Treatment A
MK-8266 orally twice daily (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.
Drug: Treatment B
MK-8266 0.1 mg orally every 2 hours (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.
Drug: Treatment C
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.
Experimental: Part I - Sequence CAB
Treatment C in Period 1, Treatment A in Period 2, and Treatment B in Period 3
Drug: Treatment A
MK-8266 orally twice daily (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.
Drug: Treatment B
MK-8266 0.1 mg orally every 2 hours (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.
Drug: Treatment C
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.
Experimental: Part I - Sequence CBA
Treatment C in Period 1, Treatment B in Period 2, and Treatment A in Period 3
Drug: Treatment A
MK-8266 orally twice daily (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.
Drug: Treatment B
MK-8266 0.1 mg orally every 2 hours (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.
Drug: Treatment C
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.
Experimental: Part II - Sequence DEF
Treatment D in Period 1, Treatment E in Period 2, and Treatment F in Period 3
Drug: Treatment D
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.
Drug: Treatment E
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.
Drug: Treatment F
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.
Experimental: Part II - Sequence DFE
Treatment D in Period 1, Treatment F in Period 2, and Treatment E in Period 3
Drug: Treatment D
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.
Drug: Treatment E
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.
Drug: Treatment F
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.
Experimental: Part II - Sequence EFD
Treatment E in Period 1, Treatment F in Period 2, and Treatment D in Period 3
Drug: Treatment D
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.
Drug: Treatment E
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.
Drug: Treatment F
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.
Experimental: Part II - Sequence EDF
Treatment E in Period 1, Treatment D in Period 2, and Treatment F in Period 3
Drug: Treatment D
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.
Drug: Treatment E
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.
Drug: Treatment F
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.
Experimental: Part II - Sequence FDE
Treatment F in Period 1, Treatment D in Period 2, and Treatment E in Period 3
Drug: Treatment D
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.
Drug: Treatment E
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.
Drug: Treatment F
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.
Experimental: Part II -Sequence FED
Treatment F in Period 1, Treatment E in Period 2, and Treatment D in Period 3
Drug: Treatment D
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.
Drug: Treatment E
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.
Drug: Treatment F
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.

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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: NCT01244035     History of Changes
Other Study ID Numbers: MK-8266-008, 2010-021832-32
Study First Received: November 17, 2010
Last Updated: March 14, 2011
Health Authority: Belgium: Ethics Committee

Keywords provided by Merck Sharp & Dohme Corp.:
High blood pressure

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 16, 2014