A Rising Single Dose Study of the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics of MK-8892 (MK-8892-001)

NCT01798849 | Completed Phase 1 Results

• 2 other identifiers: 8892-0012012-005472-34
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will evaluate safety, tolerability and effects on central diastolic blood pressure (cDBP) of MK-8892 given as single oral doses in healthy male participants (Panel A and B) and in male participants with mild-to-moderate hypertension (Panel C).

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (6)

• Percentage of Participants Who Report 1 or More Adverse Events (AEs)- Healthy Participants

  An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.

  up to 7 weeks

• Percentage of Participants Who Were Discontinued From the Study Due to an AE- Healthy Participants

  An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.

  up to 7 weeks

• Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP)- Healthy Participants

  Central diastolic blood pressure measurements were obtained at predose and at 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

  Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)

• Percentage of Participants Who Report 1 or More Adverse Events (AEs) - Hypertensive Participants

  An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized. Adverse events were summarized by dose taken at the time of the event.

  up to 7 weeks

• Percentage of Participants Who Were Discontinued From the Due to an AE - Hypertensive Participants

  An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE was summarized. Adverse events were summarized by dose taken at the time of the event.

  up to 7 weeks

• Change in 24-hour Time-weighted Average (TWA0-24hr) for Central Diastolic Blood Pressure (cDBP) - Hypertensive Participants

  Central diastolic blood pressure measurements were obtained at predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose via applanation tonometry of the radial artery. The average central diastolic blood pressure over the 24-hour monitoring period was calculated for each dose of each panel by adjusting each time-point by the baseline, aggregating the area under the curve (AUC) by the trapezoidal method and then dividing the AUC by 24 hours. A negative number indicates a decrease.

  Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period)

Secondary Outcomes (23)

• Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Healthy Participants

  Predose and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)

• Change in TWA0-24hrs for Heart Rate (HR) - Healthy Participants

  Predose (baseline) and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)

• Change in TWA0-24hr for Augmentation Index (AIx) - Healthy Participants

  Predose (baseline) and 2, 4, 12, and 24 hours postdose (for each Dosing Period of Each Panel)

• Change in TWA0-24hrs for Peripheral Diastolic Blood Pressure (pDBP) - Hypertensive Participants

  Predose (baseline) and 2, 3, 4, 6, 8, 12, 16 and 24 hours postdose (for each Dosing Period of Each Panel)

• Change in TWA0-24hrs for Heart Rate (HR) - Hypertensive Participants

  Predose and every 30 minutes from 0.5-4 hours postdose; hourly from 4-12 hours postdose; every 2 hours from 12-16 hours postdose; and at 24 postdose (for each Dosing Period of Each Panel)

Study Arms (3)

Panel A-Healthy

EXPERIMENTAL

Within each of the 5 rising dose treatment periods, 6 participants received a single dose of MK-8892 0.5 mg, 2.0 mg, 6.0 mg, 14 mg or 2.0 mg fed, and 2 participants received placebo. Dosing periods will alternate with Panel B.

Drug: MK-8892; Drug: Placebo for MK-8892

Panel B-Healthy

EXPERIMENTAL

Within each of the 4 rising dose treatment periods, 6 participants received a single dose of MK-8892 1.0 mg, 4.0 mg, 9.0 mg or 12 mg, and 2 participants received placebo. Dosing periods will alternate with Panel A.

Drug: MK-8892; Drug: Placebo for MK-8892

Panel C-Mild/Moderate Hypertension

EXPERIMENTAL

Within each of the 5 single dose treatment periods, 6 participants with mild to moderate hypertension received a single dose of MK-8892 0.5 mg, 1.0 mg, 2.0 mg or 6.0 mg, and 2 participants received placebo. Dosages will be determined by the results of Panels A and B.

Drug: MK-8892; Drug: Placebo for MK-8892

Interventions

MK-8892 DRUG

Panel A-Healthy; Panel B-Healthy; Panel C-Mild/Moderate Hypertension

Placebo for MK-8892 DRUG

Panel A-Healthy; Panel B-Healthy; Panel C-Mild/Moderate Hypertension

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Systolic blood pressure (SBP) \> 110 and ≤ 140 mmHg for Panels A and B, SBP values of 140-175 mmHg and diastolic blood pressure (DBP) of 90-105 mmHg on at least three different occasions at the prestudy (screening) visit for Panel C. Participants being treated with medication for their hypertension may be included as long as they are titrated off of their medication
• Body Mass Index (BMI) ≥ 18 kg/m\^2 and ≤ 32 kg/m\^2
• Healthy (with the exception of hypertensive subjects in Panel C)
• No clinically significant abnormality on electrocardiogram (ECG)
• No history of clinically significant cardiac disease
• No history of heart failure
• Nonsmoker and/or has not used nicotine or nicotine-containing products for at least 6 months

You may not qualify if:

• Mentally or legally incapacitated
• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal, cardiovascular (except mild to moderate hypertension), hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• Functional disability that can interfere with rising from a sitting position to the standing position
• History of cancer (malignancy)
• History of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
• Positive for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)
• Has had major surgery, donated or lost 1 unit of blood or participated in another investigational study within 4 weeks
• Has participated in another investigational trial within 4 weeks
• Unable to refrain from or anticipates the use of any medication during the study
• Anticipates using medication for erectile dysfunction during the study
• Uses or anticipates using organic nitrates during the study (e.g. nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, pentaerythritol)
• Anticipates using cytochrome P450 inhibitors (e.g. ketoconazole) or inducers (e.g. rifampin) during the study
• Consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages per day
• Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, or other caffeinated beverages per day

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

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

ClinicalTrialDisclosure@merck.com

1-800-672-6372

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
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2013
• First Posted: February 26, 2013
• Study Start: March 15, 2013
• Primary Completion: July 17, 2013
• Study Completion: July 17, 2013
• Last Updated: July 22, 2019
• Results First Posted: July 22, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will share