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

November 17, 2010
March 14, 2011
August 2010
December 2010   (final data collection date for primary outcome measure)
  • 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 ]
Same as current
Complete list of historical versions of study NCT01244035 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
A Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Different Dosing Regimens of MK-8266 in Participants With Hypertension (MK-8266-008 AM1)(COMPLETED)
Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics Following Different Dosing Regimens of MK-8266 or Placebo in Subjects With Hypertension

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.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Hypertension
  • 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.
  • 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 I - Sequence ABC
    Treatment A in Period 1, Treatment B in Period 2, and Treatment C in Period 3
    Interventions:
    • Drug: Treatment A
    • Drug: Treatment B
    • Drug: Treatment C
  • Experimental: Part I - Sequence ACB
    Treatment A in Period 1, Treatment C in Period 2, and Treatment B in Period 3
    Interventions:
    • Drug: Treatment A
    • Drug: Treatment B
    • Drug: Treatment C
  • Experimental: Part I - Sequence BCA
    Treatment B in Period 1, Treatment C in Period 2, and Treatment A in Period 3
    Interventions:
    • Drug: Treatment A
    • Drug: Treatment B
    • Drug: Treatment C
  • Experimental: Part I - Sequence BAC
    Treatment B in Period 1, Treatment A in Period 2, and Treatment C in Period 3
    Interventions:
    • Drug: Treatment A
    • Drug: Treatment B
    • Drug: Treatment C
  • Experimental: Part I - Sequence CAB
    Treatment C in Period 1, Treatment A in Period 2, and Treatment B in Period 3
    Interventions:
    • Drug: Treatment A
    • Drug: Treatment B
    • Drug: Treatment C
  • Experimental: Part I - Sequence CBA
    Treatment C in Period 1, Treatment B in Period 2, and Treatment A in Period 3
    Interventions:
    • Drug: Treatment A
    • Drug: Treatment B
    • Drug: Treatment C
  • Experimental: Part II - Sequence DEF
    Treatment D in Period 1, Treatment E in Period 2, and Treatment F in Period 3
    Interventions:
    • Drug: Treatment D
    • Drug: Treatment E
    • Drug: Treatment F
  • Experimental: Part II - Sequence DFE
    Treatment D in Period 1, Treatment F in Period 2, and Treatment E in Period 3
    Interventions:
    • Drug: Treatment D
    • Drug: Treatment E
    • Drug: Treatment F
  • Experimental: Part II - Sequence EFD
    Treatment E in Period 1, Treatment F in Period 2, and Treatment D in Period 3
    Interventions:
    • Drug: Treatment D
    • Drug: Treatment E
    • Drug: Treatment F
  • Experimental: Part II - Sequence EDF
    Treatment E in Period 1, Treatment D in Period 2, and Treatment F in Period 3
    Interventions:
    • Drug: Treatment D
    • Drug: Treatment E
    • Drug: Treatment F
  • Experimental: Part II - Sequence FDE
    Treatment F in Period 1, Treatment D in Period 2, and Treatment E in Period 3
    Interventions:
    • Drug: Treatment D
    • Drug: Treatment E
    • Drug: Treatment F
  • Experimental: Part II -Sequence FED
    Treatment F in Period 1, Treatment E in Period 2, and Treatment D in Period 3
    Interventions:
    • Drug: Treatment D
    • Drug: Treatment E
    • Drug: Treatment F
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
31
December 2010
December 2010   (final data collection date for primary outcome measure)

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
Male
21 Years to 60 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01244035
MK-8266-008, 2010-021832-32
No
Vice President, Late Stage Development Group Leader, Merck Sharp & Dohme Corp
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP