Safety, pharmacokinetics and efficacy study of QCC374 in PAH patients
- Conditions
- Pulmonary arterial hypertensionMedDRA version: 20.0Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2016-001412-38-DE
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 8
• 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):
• Idiopathic PAH
• familial PAH
• 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.
Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
• 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 or subjects with PAH responsive to high dose calcium channel blockers.
• 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.
• Hypotensive subjects (systemic systolic blood pressure < 85 mmHg)
• Subjects with left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease and/or pulmonary venous hypertension, as determined by history or echocardiogram at baseline visit.
• Subjects with obstructive (FEV1/ FVC < 70% predicted and FEV1 < 70% predicted) or restrictive (total lung capacity < 65% predicted and/or clinically significant abnormality on CXR) lung disease at screening.
Other protocol-defined exclusion criterias may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the efficacy of 16 weeks of QCC374 administration in adult patients with PAH;Secondary Objective: • To evaluate the safety and tolerability of multiple doses of QCC374 in patients with PAH<br>• To evaluate the preliminary efficacy of 16 weeks of QCC374 administration in patients with PAH by measuring changes from baseline in:<br>- Six minute walk distance (6MWD) <br>- Hemodynamic parameters other than PVR<br>- Right ventricular (RV) function with echocardiography<br>• To evaluate the pharmacokinetics of QCC374 and its metabolite QCM441 in patients with PAH;Primary end point(s): Percentage of the baseline PVR at week 16;Timepoint(s) of evaluation of this end point: 16 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • AEs, SAEs and all safety assessments<br>• 6MWD<br>• mPAP, PCWP, CO, SVR<br>• Key RV function endpoints with echocardiography including but not limited to tricuspid annular peak systolic velocity (TA S'), RV Tei index and RV fractional area change. <br>• PK parameters of primary interest (Cmax Tmax, AUClast, AUCtau) of QCC374 and QCM441 in plasma.;Timepoint(s) of evaluation of this end point: 16 weeks