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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 (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01244035
First received: November 17, 2010
Last updated: November 24, 2014
Last verified: November 2014
  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
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: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01244035     History of Changes
Other Study ID Numbers: 8266-008, 2010-021832-32
Study First Received: November 17, 2010
Last Updated: November 24, 2014
Health Authority: Belgium: Ethics Committee

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

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 24, 2014