This Study evaluates the pharmacokinetic (PK) profile of different zamicastat doses in Pulmonary arterial hypertension (PAH) patients to find the most promising therapeutic dosage range for the treatment of PAH disease
Who can participate
Age range18 Years – 70 Years
SexALL
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Inclusion criteria
✓. Male or female patients aged 18 to 70 years.
✓. Able to comprehend and willing to sign an informed consent form.
✓. Diagnosis of PAH (pulmonary arterial hypertension WHO Group 1), documented by right heart catheterisation with a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, a pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg and a pulmonary vascular resistance (PVR) \> 3 wood unit (WU):
✓. Idiopathic, in non-vasoreactive patients
✓. Heritable: Bone morphogenetic protein receptor type II (BMPR2) mutation and other mutations, in non-vasoreactive patients
✓. Drugs and toxin induced, in non-vasoreactive patients
✓. Associated with connective tissue disease
✓. Associated with simple congenital defects (atrial septal defect and/or ventricular septal defect) if closed \> 12 months before inclusion.
Exclusion criteria
✕. Contraindication to zamicastat, i.e. known hypersensitivity to ingredients of zamicastat formulation.
✕. Two or more consecutive measurements of systolic blood pressure (SBP) \< 95 mmHg or diastolic blood pressure (DBP) \< 50 mmHg.
✕. Uncontrolled diabetes mellitus with HbA1c ≥ 8.5% within the last three months or at screening.
✕. PAH WHO Group 1 due to portal hypertension, human immunodeficiency virus (HIV) infection and schistosomiasis.
What they're measuring
1
Area Under the Curve 0-24h (AUC0-24h) (ng.h/mL) - 50 mg
Timeframe: Day 1 (0 hours and then 1, 2, 4, 8, 16 and 24 hours after investigational medicinal product (IMP) intake)
2
Area Under the Curve 0-24h (AUC0-24h) (ng.h/mL/mg) - HTD
Timeframe: 1, 2, 4, 8, 16 and 24 hours after IMP intake
3
Maximum Plasma Concentration (Cmax) (ng/mL) - 50 mg
Timeframe: Day 1 (0 hours and then 1, 2, 4, 8, 16 and 24 hours after IMP intake)
4
Maximum Plasma Concentration (Cmax) (ng/mL/mg) - HTD
Timeframe: 1, 2, 4, 8, 16 and 24 hours after IMP intake
5
Time Until Cmax (Tmax) (h) - 50 mg
Timeframe: Day 1 (0 hours and then 1, 2, 4, 8, 16 and 24 hours after IMP intake)
6
Time Until Cmax (Tmax) (h) - HTD
Timeframe: 1, 2, 4, 8, 16 and 24 hours after IMP intake
7
Minimum Plasma Concentration at the End of the Dosing Interval (Cmin,SS) (ng/mL/mg) - HTD
Timeframe: 1, 2, 4, 8, 16 and 24 hours after IMP intake
✕. Any disease known to cause pulmonary hypertension other than PAH WHO Group 1.
✕. Obstructive lung disease: Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV1/FVC) \< 60% and FEV1 \< 60% of predicted value after bronchodilator administration.
✕. Restrictive lung disease: Total Lung Capacity (TLC) \< 70% of predicted value.
✕. History of moderate to severe hepatic impairment (Child-Pugh B and C).