Multi centre study to assess the safety, effective and movement of Zamicastat within the body when given to a patient with pulmonary arterial hypertension as an additional medication.
- Conditions
- Pulmonary arterial hypertensionMedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-002448-10-GB
- Lead Sponsor
- Bial - Portela & Ca, S.A
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 32
1. Male or female patients aged 18 to 75 years inclusive.
2. Able to comprehend and willing to sign an informed consent form (ICF).
3. Diagnosis of PAH (pulmonary arterial hypertension WHO Group 1) documented by RHC with a mPAP = 25 mmHg, a PAWP = 15 mmHg and a PVR > 3 WU [7,8]:
e) Idiopathic, in non-vasoreactive patients
f) Heritable: Bone morphogenetic protein receptor type II (BMPR2) mutation and
other mutations, in non-vasoreactive patients
g) Drugs and toxin induced, in non-vasoreactive patients
h) 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. The patient’s last right heart catheterisation results, which were measured at the study site, must not be older than 90 days before V1 (will be considered as baseline value). Otherwise a right heart catheterisation has to be performed as part of the study at visit A1.
5. WHO functional class II or III as judged by the investigator.
6. 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.
7. For women: Agree not to donate ova from the time of informed consent until 30 days after the last IMP intake.
For men: Agree not to donate sperm from the time of informed consent until 90 days after the last IMP intake.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
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 measured at V1.
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), as demonstrated and documented by previous spirometry data which, in the opinion of the investigator, represent the clinical state of the patient at the time of the screening visit.
7. Restrictive lung disease: Total Lung Capacity (TLC) < 70% of predicted value, as demonstrated and documented by previous spirometry data which, in the opinion of the investigator, represent the clinical state of the patient at the time of the screening visit.
8. History of moderate to severe hepatic impairment (Child-Pugh B and C).
9. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at V1).
10. se 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.
11. Current or previous (within the past year) alcohol or substance abuse excluding caffeine or nicotine.
12. 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.
13. For women: Pregnancy or breast-feeding. Women of childbearing potential (as defined in Section 4.2) unable or unwilling to undergo pregnancy tests and practice highly effective contraceptive measures in combination with a barrier method e.g. condom (without spermicidal foam/gel/film/cream/suppository or fat- or oil-containing lubricants), occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository from the time of informed consent until 30 days after last IMP intake. Highly effective methods for women are surgical intervention (e.g. bilateral tubal occlusion), non-hormonal implantable intrauterine device, true sexual abstinence (i.e. when this is in line with the preferred and usual lifestyle of the patient) and vasectomised partner (provided that the partner is the sole sexual partner of the patient and the partner has received medical assessment of the surgical success).Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods), hormonal contraceptives and withdrawal are not acceptable methods of contraception.
For men: Male patients who are sexually active with a partner of childbearing potential must use, with their partner, a condom plus an approved acceptable contraceptive measure from the time of informed consent until 90 days after the last IMP intake. The following methods are acceptable methods of contraception: partner’s use of combined (oestrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); partner’s
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