Pulmonary arterial hypertension MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Bial - Portela & Ca, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have performed MPV3 of the preceding study BIA-51058-201. 2. Able to comprehend and willing to sign an informed consent form 3. 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: 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
Exclusion criteria: 1. Significant non-compliance with the protocol during the preceding study BIA-51058-201 which may have an impact on this extension study. 2. WHO functional class IV as judged by the investigator. 3. Two or more consecutive measurements of systolic blood pressure (SBP) < 95 mmHg or diastolic blood pressure (DBP) < 50 mmHg measured at visit V1. 4. Uncontrolled diabetes mellitus with HbA1c = 8.5% within the last three months or at visit V1. 5. Occurrence of an AE during the preceding study which is judged by the investigator as contraindicative to further participation in the extension study. 6. Any disease known to cause pulmonary hypertension other than PAH WHO Group 1. 7. Obstructive lung disease: Forced Expiratory Volume in 1 second/Forced Vital Capacity (FEV1/FVC) < 60% and FEV1 < 60% of predicted value after bronchodilator administration, 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 visit V1. 8. 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 visit V1. 9. History of moderate to severe hepatic impairment (Child-Pugh B and C). 10. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at MPV1 of study BIA-51058-201). 11. 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. 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. inal Version 2.0, 20-AUG-2019 CONFIDENTIAL Page 12 of 76 13. For women: Pregnancy or breast-feeding. Women of childbearing potential 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 fator 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 the last IMP intake. Highly effective methods for women are surgical intervention (e.g. bilateral tubal occlusion), nonhormonal 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:
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the safety and tolerability of the individual highest tolerated zamicastat doses, achieved in the study BIA-51058-201, during long-term treatment in PAH disease.;Secondary Objective: To assess further efficacy, safety and tolerability parameters of the individual highest tolerated zamicastat doses in long-term treatment of PAH. ;Primary end point(s): The safety and tolerability of the used zamicastat doses will be evaluated by: 1. Adverse events 2. Clinically relevant changes in laboratory parameters (haematology, biochemistry, urinalysis) 3. Clinically relevant changes in vital signs 4. Clinically relevant changes in ECG parameters 5. Incidence of new scars (only in patients with scleroderma) 6. Skin score (only in patients with scleroderma) ;Timepoint(s) of evaluation of this end point: As soon as the last subject has completed the last visit and all data have been locked, the results will be analysed and described in a Clinical Study Report. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline* to V5 (if applicable) and from V1 to V5 (if applicable) for the following parameters: 1. Pulmonary vascular resistance (PVR), right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2). Further haemodynamic parameters may also be calculated if considered appropriate. Change from baseline* to V3 and to V5 and from V1 to V5 for the following parameters: 2. WHO functional class 3. 6-minute walk test (6-MWT), including Borg dyspnoea score 4. Biomarkers (brain natriuretic peptide [BNP] and N-terminal pro brain natriuretic peptide [NT-proBNP]) 5. Echocardiogram parameters: • Tricuspid regurgitation, classified as absent, mild, moderate or severe • Right ventricular contractility, measured via tricuspid annular plane systolic excursion (TAPSE) • Pericardial effusion, classified as absent, traces or present • Right atrial area (end-systolic), right ventricular end-diastolic area 6. Quality of life (SF-36v2);Timepoint(s) of evaluation of this end point: As soon as the last subject has completed the last visit and all data have been locked, the results will be analysed and described in a Clinical Study Report. | — |
Countries
Austria, Germany, Italy, Portugal, Spain, Ukraine, United Kingdom
Contacts
Public ContactDevelopment Department
Bial - Portela & Ca, S.A.
Outcome results
None listed