Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients
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This is a non-confirmatory, randomized, subject and investigator blinded, placebo controlled study of QCC374 in PAH patients. The study will have 2 parts. In Part 1, an initial safety cohort, 8 subjects will be randomized in a 6:2 ratio and the starting dose will be 0.03 mg b.i.d.. In Part 2, ~ 30 subjects will be randomized in a 2:1 ratio, with a planned starting dose of 0.06 mg b.i.d.. In both Parts, subjects will be up-titrated during the first two weeks of the study to 0.12 mg b.i.d, or to their maximum tolerated dose (MTD) if their individual MTD is below 0.12 mg b.i.d. during the first two weeks of the study. The treatment duration is 16 weeks.
A Randomized, Parallel-group, Placebo-controlled Subject and Investigator Blinded Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of QCC374 in the Treatment of Pulmonary Arterial Hypertension
Actual Study Start Date :
September 19, 2017
Estimated Primary Completion Date :
December 27, 2018
Estimated Study Completion Date :
December 27, 2018
Resource links provided by the National Library of Medicine
Efficacy of 16 weeks of QCC374 administration in adult patients with PAH [ Time Frame: 16 weeks ]
Percentage of the baseline PVR at week 16
Secondary Outcome Measures :
Change from Baseline in Six Minute Walk Test (6MWT) [ Time Frame: 16 weeks ]
Six Minute Walk Distance (6MWD)
Change from Baseline in Right Heart Catheterization (RHC) Measurements [ Time Frame: 16 Weeks ]
The RHC assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including mean pulmonary arterial pressure (PAP), Pulmonary Capillary Wedge Pressure (PCWP), cardiac output (CO), pulmonary vascular resistance (PVR) and Systemic Vascular Resistance (SVR).
Change from Baseline in Echocardiography Measurements [ Time Frame: 16 weeks ]
Key right ventricular (RV) function endpoints with echocardiography will include but not limited to tricuspid annular peak systolic velocity (TA S'), RV Tei index and RV fractional area change.
Cmax [ Time Frame: 16 weeks ]
Cmax is the observed maximum plasma concentration following drug administration
Tmax [ Time Frame: 16 weeks ]
Tmax is the time to reach the maximum concentration after drug administration
AUClast [ Time Frame: 16 weeks ]
AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
AUCtau [ Time Frame: 16 weeks ]
The area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau [mass x time / volume]
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Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Male and female patients 18 years of age or older with symptomatic PAH.
Subjects with PAH belonging to one of the following subgroups of the Updated Clinical Classification Group 1 (Nice, 2013):
PAH associated with connective tissue disease, congenital heart disease (surgically repaired at least 12 months prior to screening) or drug or toxin induced (for example, anorexigen use).
Subjects must have persistent symptoms due to PAH despite therapy with at least one of the following PAH medications: an endothelin receptor antagonist, asoluble guanylate cyclase stimulator or a phosphodiesterase inhibitor. The subjects' PAH medication regimen, with typical medications including calcium channel blockers, endothelin receptor antagonists, soluble guanylate cyclase stimulators and/or phosphodiesterase inhibitors, must have been used at a stable dose and frequency for at least 12 weeks before the screening visit and during the screening period.
Diagnosis of PAH established according to the standard criteria before the screening visit:
Resting mean pulmonary arterial pressure > 25 mmHg.
PVR > 240 dynes s/cm5.
Pulmonary capillary wedge pressure or left ventricular end diastolic pressure < 15 mmHg
PVR > 400 dynes s/cm5 at the time of the baseline right heart catheterization (RHC) (if a RHC was completed within one month of the screening visit, that result may be used for inclusion).
6-minute walk distance greater than 150 meters at Screening. This distance must be confirmed by a second 6MWT prior to randomization. The value of the second 6MWD should be within ± 15% of the value obtained at Screening.
Subjects with clinically unstable right heart failure within the last three months (New York Heart Association (NYHA) Class IV).
Subjects with PAH associated with portal hypertension, Human Immunodeficiency Virus (HIV) infection or unrepaired congenital systemic to pulmonary shunts
Subjects who have received or have been scheduled to receive long-term treatment with epoprostenol or any prostacyclin within the three months prior to the screening visit or during the screening period.
Subjects with a history of left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease and/or pulmonary venous hypertension.
Subjects with significant obstructive (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] < 70% predicted) or restrictive (total lung capacity < 70% predicted) lung disease at screening.