Clinical trial NCT01934647: Acute Dosing of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-003)
Official title: A Non-randomized, Single-Panel, Open-Label Trial to Study the Safety, Tolerability and Pharmacodynamics of MK-8892 Acute Dosing in Subjects With Moderate to Severe Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-09-04
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892
timeFrame: Baseline and up to 5 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: