Acute Dosing of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-003)

NCT01934647 | Terminated Phase 1 Results

• 3 other identifiers: 8892-0032013-001680-23MK-8892-003
• Study Type: interventional
• Target: 7
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical trial will study the safety, tolerability, and pharmacodynamics of single doses of MK-8892 in participants with pulmonary arterial hypertension (PAH). The primary objective is to estimate the measured peak effect of the highest acutely tolerated (HAT) single oral dose of MK-8892 on pulmonary vascular resistance (PVR).

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892

  PVR assessments were performed throughout the right heart catheterization (RHC). Peak PVR reduction was determined to occur if 2 consecutive PVR measurements were at least 20% greater than the nadir PVR measurement.

  Baseline and up to 5 hours post-dose

Study Arms (3)

1 mg MK-8892

EXPERIMENTAL

Participants will receive a single oral dose of 1 mg MK-8892.

Drug: MK-8892

4 mg MK-8892

EXPERIMENTAL

Participants will receive a single oral dose of 4 mg MK-8892.

Drug: MK-8892

8 mg MK-8892

EXPERIMENTAL

Participants will receive a single oral dose of 8 mg MK-8892.

Drug: MK-8892

Interventions

MK-8892 DRUG

Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892

1 mg MK-8892; 4 mg MK-8892; 8 mg MK-8892

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• postmenopausal female or if female of reproductive potential, remains abstinent or uses two acceptable methods of birth control during 14 days after dosing with MK-8892
• has suspected PAH classified in one of the following sub-groups: idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease, as defined by the Dana Point 2008 Clinical Classification
• has a clinical indication for right heart catheterization
• PAH classified as World Health Organization (WHO) functional class II or III

You may not qualify if:

• has a medical history indicating a secondary cause of Pulmonary Hypertension (PH) or a non-included etiology of PAH including the following tests within 6 months of Visit 1: Echo indicating significant left heart disease, valvular disease, or structural defects; function test indicating significant pulmonary disease; imaging test indicating veno-occlusive disease; perfusion scan indicating thromboembolic disease; abdominal ultrasound indicating cirrhosis; positive test for human immunodeficiency virus (HIV)
• has persistent or permanent atrial fibrillation, significantly impaired gas exchange, history of radiation of the lung or mediastinum, hepatic or hepatobiliary disease, immunodeficiencies or latent bleeding risk
• has estimated Glomerular Filtration Rate (GFR) \<45 mL/min
• has alanine aminotransferase test (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate aminotransferase test (AST) serum glutamic oxaloacetic transaminase (SGOT) \>= 3 x upper limit of normal (ULN) at Visit 1
• has a systolic blood pressure (BP) \<105 mmHg, or heart rate (HR) \> 100 beats/min at Visit 1 (Day -7 to -1)
• has previously received specific therapy for PAH within 4 weeks prior to Visit 1
• has taken sildenafil, valdenafil or a nitrate within 24 hours prior to Visit 2 date
• has taken tadalafil within 7 days prior to Visit 2 date
• has taken 2 or more specific PAH medications concomitantly within 4 weeks of anticipated Visit 2 date. Only treatment naïve subjects or subjects on stable PAH-specific monotherapy with an endothelin receptor antagonist (\[ERA\]; bosentan, ambrisentan, or macitentan) or a prostacyclin analog (\[PCA\]; treprostinil, epoprostenol, or iloprost) are eligible. PAH monotherapy with one of these medications may continue without interruption during this study
• has taken a soluble guanylate cyclase (sGC) activator (riociguat) within 24 hours of anticipated Visit 2 date.
• has taken diltiazem immediate release within 1 day or diltiazem extended release within 2 days prior to Visit 2 date
• is currently taking potent inhibitors or inducers of Cytochrome P450 3A4 (CYPA4), or is consuming \>1 liter of grapefruit juice per day
• is pregnant or breastfeeding or expecting to conceive during study or post study follow-up period
• has donated 500 mL of blood within prior 60 days
• is currently participating in or has within the prior three months participated in a study with an investigational compound or device

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.

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2013
• First Posted: September 4, 2013
• Study Start: November 22, 2013
• Primary Completion: September 8, 2014
• Study Completion: September 8, 2014
• Last Updated: October 22, 2018
• Results First Posted: October 22, 2018

Record last verified: 2018-03