Safety, Pharmacodynamics, and Pharmacokinetics of Different Dosing Regimens of MK-8266 in Participants With Hypertension (MK-8266-008)

NCT01244035 | Completed Phase 1 Results

• 2 other identifiers: 8266-0082010-021832-32
• Study Type: interventional
• Target: 31
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was designed as 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. Only Part I of the study was completed.

Conditions

Hypertension

Keywords

High blood pressure

Outcome Measures

Primary Outcomes (9)

• Adverse Events (AEs)

  The number of participants with one or more clinical or laboratory AEs was assessed. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.

  MK-8266 1.3 mg BID and 0.9 mg FDD groups: Up to Day 4 in each period; MK-8266 1 mg QD group: the last AE was reported on day 10 after the last dose; Placebo group: Up to 10-14 days after the last dose of placebo

• Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Days 1 and 3

  The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided.

  Pre-dose and 0.5, 1, 2, 4, and 8 hours after dosing on Day 1, and pre-dose and 4 and 8 hours after dosing on Day 3 of each period

• Area Under the MK-8266 Concentration Versus Time Curve AUC(0-8 Hours) on Day 4

  The AUC(0-8 hours) of MK-8266 was assessed. The arithmetic mean and standard deviation values of AUC(0-8 hours), based on the raw scale, are provided.

  Predose and 2, 4, and 8 hours after dosing on Day 4 of each period

• Maximum Plasma Concentration (Cmax) of MK-8266 on Day 1 and Day 3

  The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided.

  Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3

• Maximum Plasma Concentration (Cmax) of MK-8266 on Day 4

  The Cmax of MK-8266 was assessed. The arithmetic mean and standard deviation values of Cmax, based on the raw scale, are provided.

  Predose and 2, 4, and 8 hours after dosing on Day 4 of each period

• Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 1 and Day 3

  The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 1 and Day 3.

  Pre-dose and 0.5, 1, 2, 4, 8, 12, 14, 15, and 16 hours after dosing on Days 1 and 3

• Time to Maximum Plasma Concentration (Tmax) of MK-8266 on Day 4

  The Tmax of MK-8266 was assessed. Descriptive statistics are provided for the minimum, median and maximum values for the Tmax of MK-8266 on Day 4.

  Predose and 2, 4, and 8 hours after dosing on Day 4 of each period

• Change From Baseline in Heart Rate (HR)

  The effect of MK-8266 and placebo on changes in HR were assessed, as measured by time weighted average change from baseline in HR over 0-24 hours postdose (TWA\^0-24 hr) on Day 3. Baseline values for HR are shown in the Baseline Characteristics section.

  Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3

• Change From Baseline in Diastolic Blood Pressure (DBP)

  The effect of MK-8266 and placebo on changes in diastolic blood pressure (DBP) were assessed, as measured by time weighted average change from baseline in DBP over 0-24 hours postdose (TWA\^0-24 hr) on Day 3. Baseline values for DBP are shown in the Baseline Characteristics section.

  Pre-dose (Baseline) and every 30 minutes for the first 4 hours, followed by hourly up to 24 hours after dosing on Day 3

Study Arms (12)

Part I - Sequence ABC

EXPERIMENTAL

Treatment A in Period 1, Treatment B in Period 2, and Treatment C in Period 3

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Part I - Sequence ACB

EXPERIMENTAL

Treatment A in Period 1, Treatment C in Period 2, and Treatment B in Period 3

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Part I - Sequence BCA

EXPERIMENTAL

Treatment B in Period 1, Treatment C in Period 2, and Treatment A in Period 3

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Part I - Sequence BAC

EXPERIMENTAL

Treatment B in Period 1, Treatment A in Period 2, and Treatment C in Period 3

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Part I - Sequence CAB

EXPERIMENTAL

Treatment C in Period 1, Treatment A in Period 2, and Treatment B in Period 3

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Part I - Sequence CBA

EXPERIMENTAL

Treatment C in Period 1, Treatment B in Period 2, and Treatment A in Period 3

Drug: Treatment A; Drug: Treatment B; Drug: Treatment C

Part II - Sequence DEF

EXPERIMENTAL

Treatment D in Period 1, Treatment E in Period 2, and Treatment F in Period 3

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Part II - Sequence DFE

EXPERIMENTAL

Treatment D in Period 1, Treatment F in Period 2, and Treatment E in Period 3

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Part II - Sequence EFD

EXPERIMENTAL

Treatment E in Period 1, Treatment F in Period 2, and Treatment D in Period 3

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Part II - Sequence EDF

EXPERIMENTAL

Treatment E in Period 1, Treatment D in Period 2, and Treatment F in Period 3

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Part II - Sequence FDE

EXPERIMENTAL

Treatment F in Period 1, Treatment D in Period 2, and Treatment E in Period 3

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Part II -Sequence FED

EXPERIMENTAL

Treatment F in Period 1, Treatment E in Period 2, and Treatment D in Period 3

Drug: Treatment D; Drug: Treatment E; Drug: Treatment F

Interventions

Treatment A DRUG

MK-8266 1.3 mg orally twice daily (BID, 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.

Also known as: MK-8266 1.3 mg BID

Part I - Sequence ABC; Part I - Sequence ACB; Part I - Sequence BAC; Part I - Sequence BCA; Part I - Sequence CAB; Part I - Sequence CBA

Treatment B DRUG

MK-8266 0.1 mg orally administered every 2 hours as frequent divided dosing (FDD, 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.

Also known as: MK-8266 0.9 mg FDD

Part I - Sequence ABC; Part I - Sequence ACB; Part I - Sequence BAC; Part I - Sequence BCA; Part I - Sequence CAB; Part I - Sequence CBA

Treatment C DRUG

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.

Also known as: Placebo

Part I - Sequence ABC; Part I - Sequence ACB; Part I - Sequence BAC; Part I - Sequence BCA; Part I - Sequence CAB; Part I - Sequence CBA

Treatment D DRUG

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.

Part II - Sequence DEF; Part II - Sequence DFE; Part II - Sequence EDF; Part II - Sequence EFD; Part II - Sequence FDE; Part II -Sequence FED

Treatment E DRUG

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.

Part II - Sequence DEF; Part II - Sequence DFE; Part II - Sequence EDF; Part II - Sequence EFD; Part II - Sequence FDE; Part II -Sequence FED

Treatment F DRUG

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.

Part II - Sequence DEF; Part II - Sequence DFE; Part II - Sequence EDF; Part II - Sequence EFD; Part II - Sequence FDE; Part II -Sequence FED

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hypertension

Interventions

BID protein, human

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 19, 2010
• Study Start: August 19, 2010
• Primary Completion: December 23, 2010
• Study Completion: December 23, 2010
• Last Updated: February 28, 2019
• Results First Posted: February 28, 2019

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share