Study to find the most promising therapeutic dosage of zamicastat for the treatment of PAH disease.

Phase 1

Conditions: Pulmonary arterial hypertension
MedDRA version: 20.0Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2018-002448-10-ES

Lead Sponsor: Bial - Portela & Ca, S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 40

Inclusion Criteria

1. Male or female patients aged 18 to 65 years.
2. Able to comprehend and willing to sign an informed consent form.
3. 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 WU [Galie N, et. al 2015; Lau EMT, et. al. 2017]:
a) Idiopathic, in non-vasoreactive patients
b) Heritable: Bone morphogenetic protein receptor type II (BMPR2) mutation and other mutations, in non-vasoreactive patients
c) Drugs and toxin induced, in non-vasoreactive patients
d) Associated with connective tissue disease or with simple congenital defects (atrial septal defect and/or ventricular septal defect) if closed > 12 months before inclusion.
4. WHO functional class II or III as judged by the investigator.
5. Stable treatment with at least one of the following approved oral PAH therapies within 3 months before V1: Ambrisentan, Bosentan, Macitentan, Riociguat, Selexipag, Sildenafil or Tadalafil.
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 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1. Contraindication to zamicastat, i.e. known hypersensitivity to ingredients of zamicastat formulation.
2. Persistent hypotension defined as SBP < 95 mmHg or DBP < 50 mmHg.
3. Uncontrolled diabetes mellitus.
4. PAH WHO Group 1 due to portal hypertension, human immunodeficiency virus (HIV) infection and schistosomiasis.
5. Any disease known to cause pulmonary hypertension other than PAH WHO Group 1, e.g. obstructive lung diseases, parasitic disease affecting the pulmonary system, sickle cell anaemia, left heart disease.
6. History of moderate to severe hepatic impairment (Child-Pugh B and C).
7. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at V1).
8. Use of the following prohibited medication or treatments during study participation: calcium channel blockers (CCBs) if used for the treatment of PAH in vasoreactive patients; drugs containing a catechol group that is metabolised by DßH e.g. rimiterole, isoprenaline, dopamine, dopexamine or dobutamide) or a- and/or ß-blockers.
9. Current or previous (within the past year) alcohol or substance abuse excluding caffeine or nicotine.
10. Presence of any other significant or progressive/unstable medical condition that, in the opinion of the investigator, would compromise evaluation of the study treatment or may jeopardise the patient’s safety, compliance or adherence to protocol requirements.
11. For women: Pregnancy or breast-feeding. Women of childbearing potential unable or unwilling to undergo pregnancy tests and practice acceptable contraceptive measures. Acceptable methods for women are surgical intervention (e.g. bilateral tubal occlusion),intrauterine device, double-barrier methods and true sexual abstinence (i.e. when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
12. Previous participation in any other drug investigational study within the past 30 days (or five half-lives of investigational medicinal product [IMP] whichever is longer) prior to V1.
13. Vulnerable patients according to Section 1.61 of the ICH guideline for Good Clinical
Practice E6.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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