To study the safety and effectiveness of the maximum tolerated dose of zamicastat, found in BIA-51058-201, in the treatment of long-term PAH.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2018-002796-18-ES
• Date of registration: 16/11/2018
• Prospective Registration: Yes
• Primary sponsor: Bial - Portela & Ca, S.A.
• Public title: To study the safety and effectiveness of the maximum tolerated dose of zamicastat, found in BIA-51058-201, in the treatment of long-term PAH.
• Scientific title: An open-label, multicentre study to evaluate the safety and efficacy of zamicastat as adjunctive therapy in long-term treatment of pulmonary arterial hypertension (PAH) disease
• Date of first enrolment: 17/01/2019
• Target sample size: 40
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002796-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Portugal, Spain, Ukraine, United Kingdom

Contacts

• Name: Pilar Escribano-Subías
• Affiliation: Hospital 12 de Octubre Servicio de Cardiología

• Name: Pilar Escribano-Subías
• Affiliation: Hospital 12 de Octubre Servicio de Cardiología

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have completed MPV3 of the preceding study BIA-51058-201.
2. Able to comprehend and willing to sign an informed consent form
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. 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. Persistent hypotension defined as systolic blood pressure (SBP) < 95 mmHg or diastolic blood pressure (DBP) < 50 mmHg.
4. Uncontrolled diabetes mellitus.
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, e.g. obstructive lung diseases, parasitic disease affecting the pulmonary system, sickle cell anaemia, left heart disease.
7. History of moderate to severe hepatic impairment (Child-Pugh B and C).
8. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at V1).
9. 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.
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. Concurrent participation in any other drug investigational study, except BIA-51058-201.
13. Vulnerable patients according to Section 1.61 of the ICH guideline for Good Clinical Practice E6.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary arterial hypertension
MedDRA version: 20.0 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: Zamicastat
Product Code: BIA-5-1058
Pharmaceutical Form: Tablet
INN or Proposed INN: ZAMICASTAT
CAS Number: 1080028-80-3
Current Sponsor code: BIA 5-1058
Other descriptive name: BIA 5-1058
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: To assess further efficacy, safety and tolerability parameters of the maximum tolerated zamicastat doses in long-term treatment of PAH.

Main Objective: The primary objective of this study is to assess the safety and tolerability of the maximum tolerated zamicastat doses, achieved in the study BIA-51058-201, during long-term treatment in PAH disease.

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 Outcome(s)

Secondary end point(s): Change from baseline* to V5 and from V1 to V5 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.

Secondary ID(s)

2018-002796-18-PT

BIA-51058-202

Source(s) of Monetary Support

Bial - Portela & Ca, S.A.

Ethics review

Status: Approved
Approval date:
Contact: