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:
Merck
Information provided by:
Merck
ClinicalTrials.gov Identifier:
NCT01244035
First received: November 17, 2010
Last updated: March 14, 2011
Last verified: March 2011
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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:
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:
|
High blood pressure |
Additional relevant MeSH terms:
|
Hypertension Vascular Diseases Cardiovascular Diseases |
ClinicalTrials.gov processed this record on May 19, 2013