Pulmonary Arterial HypertensionPhase 2NCT06009185
Safety and Efficacy of BIA 5-1058 in PAH
A Phase 2 study testing Oral zamicastat in people with Pulmonary Arterial Hypertension, run by Bial - Portela C S.A. at 11 sites in 6 countries.
Trial summary
This study aims 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 Pulmonary Arterial Hypertension (PAH) disease. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- Oral zamicastat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 11 sitesin 6 countries
- Study dates
- 26 Jun 2019to 17 Feb 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For inclusion in the extension study, patients had to fulfil all of the following criteria at visit V1 (Day 1, start of the extension study):
- Have performed MPV3 of the preceding study BIA-51058-201.
- Able to comprehend and willing to sign an informed consent form (ICF).
- For women: Agreed not to donate ova from the time of informed consent until 30 days after the last IMP intake.
- For men: Agreed not to donate sperm from the time of informed consent until 90 days after the last IMP intake
Who cannot join
- Patients were to be excluded for any one of the following reasons:
- Significant non-compliance with the protocol during the preceding study BIA-51058-201 which may have an impact on this extension study.
- WHO functional class IV as judged by the investigator (reference 1)
- Two or more consecutive measurements of systolic blood pressure (SBP) < 95 mmHg or diastolic blood pressure (DBP) < 50 mmHg measured at visit V1.
- Uncontrolled diabetes mellitus with HbA1c ≥ 8.5% within the last three months or at visit V1.
- Occurrence of an AE during the preceding study which is judged by the investigator as contraindicative to further participation in the extension study.
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- 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, 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.
- 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.
- History of moderate to severe hepatic impairment (Child-Pugh B and C).
- Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (measured at Maintenance period visit 1 (MPV1) of study BIA-51058-201).
- 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 DβH (e.g. rimiterole, isoprenaline, dopamine, dopexamine or dobutamide) or α- and/or β-blockers.
- 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.
- 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 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 the 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 use of progestogen-only hormonal contraception (oral, injectable/implantable, intrauterine hormone-releasing system); partner's use of implantable intrauterine device; surgical sterilisation (for example, vasectomy or bilateral tubal occlusion).
- Concurrent participation in any other drug investigational study except BIA-51058-201.
- Vulnerable patients according to Section 1.61 of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline for Good Clinical Practice E6.
Trial locations and contacts
11 sites in 6 countries.
11 sites in 6 countries
Spain4 sites
Hospital Clinic de Barcelona Calle Villarroel, 170
Barcelona, 08036
Hospital Universitario "12 de Octubre" Avda. de Córdoba, s/n
Madrid, 28041
Complejo Asistencial Universitario de Salamanca Pº. San Vicente, 58
Salamanca, 37007
Hospital Universitario Marques de Valdecilla Avenida Valdecilla, 25
Santander, 39008
Italy2 sites
ASST di Monza-Ospedale San Gerardo -Dipartimento di Pneumologia via Pergolesi 33
Monza, 20900
AOU di Roma-Policlinico Umberto I-Unità Dipartimentale Malattie del Circolo Polmonare Viale del Policlinico 155
Roma, 00161
United Kingdom2 sites
Golden Jubilee National Hospital Golden Jubilee National Hospital Agamemnon St, Scottish Pulmonary Vascular Unit Golden Jubilee National Hospital
Clydebank, G81 4DY
Royal Free Hospital Pond Street
London, NW3 2QG
Austria1 site
Ordensklinikum Linz Elisabethinen, Interne 2 - Kardiologie, Angiologie & Interne Intensivmedizin Fadingerstraße 1
Linz, 4020
Germany1 site
Universitätsklinikum Carl Gustav Carus Dresden, Medizinische Klinik und Poliklinik I, Pneumologie Fetscherstraße 74
Dresden, 01307
Portugal1 site
Centro Hospitalar Lisboa Norte, E.P.E. - Hospital Pulido Valente Consulta Externa de Hipertensão Pulmonar Alameda das Linhas de Torres, 117
Lisbon, 1769-001
About this study
Official 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
This study aims 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 Pulmonary Arterial Hypertension (PAH) disease.
Read the detailed description
This is an extension study with Pulmonary Arterial Hypertension (PAH) patients who are under treatment with zamicastat as adjunctive therapy in the study BIA-51058-201.
For patients participating in this extension study, visit "Maintenance Period Visit 3" (MPV3) of the study BIA-51058-201 will also be the first visit (V1) of this extension study (BIA-51058-202). Their treatment with zamicastat will be continued at their individual highest tolerated dose (HTD) for an additional 12 weeks (50 mg, 100 mg, 150 mg or 200 mg).
Further visits will be performed 20 ±3 days (V2, telephone), 41 ±3 days (V3, on-site), 62 ±3 days (V4, telephone) and 83 ±3 days (V5, on-site) after V1. At V5, patients will have the opportunity to continue treatment with zamicastat in a compassionate use program. Patients who will not participate in this compassionate use program will come to the following follow-up visit(s):
- Follow-up (FU) down-titration (telephone, 14 ±2 days after V5); only applicable in patients taking 150 mg or 200 mg zamicastat
- FU visit (on-site, 14 ±2 days after last investigational medicinal product (IMP) intake).
The data and safety monitoring board (DSMB) will periodically review the safety data and will issue a recommendation if the study can be continued as planned.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- Oral zamicastat
- Keywords
- PAH, BIA 5-1058, Zamicastat, Bial, Bial - Portela & Ca, S.A., dopamine ß-hydroxylase (DßH) inhibitor, vascular obstruction, pulmonary arteries, right-heart catheterisation (RHC), idiopathic, rare lung disease
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral zamicastatDrug
Tablets for oral administration under fed conditions containing 100 mg of zamicastat. Zamicastat has to be taken in the morning after breakfast.
| Study group | Role | What they receive |
|---|---|---|
| HTD < 200 mg zamicastat | Experimental | Tablets for oral administration under fed conditions. Zamicastat has to be taken in the morning after breakfast. Each patient will continue treatment with the individual highest tolerated dose (HTD) he/she was taking at MPV3 of the study BIA-51058-201 and will take this dose until visit V5. Receives: Drug: Oral zamicastat |
| HTD 200 mg zamicastat | Experimental | Tablets for oral administration under fed conditions containing 100 mg of zamicastat (two tablets of 100 mg). Zamicastat has to be taken in the morning after breakfast. Each patient will continue treatment with the individual highest tolerated dose (HTD) he/she was taking at MPV3 of the study BIA-51058-201 and will take this dose until visit V5. Receives: Drug: Oral zamicastat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events (AEs)
The number of participants with AEs will be presented. An AE is any untoward medical occurrence in a patient to whom a medicinal product is administered and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease occurring during the course of the study.
Measured: Up to 12 weeks
Clinically relevant changes in laboratory parameters: coagulation
Based on coagulation analysis measurements of prothrombin time test (international normalized ratio). The prothrombin time (PT) test measures how long it takes for a clot to form in a blood sample. The International Normalized Ratio is a type of calculation based on PT test results. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Incidence of clinically relevant changes (abnormalities) in laboratory parameters: biochemistry
Based on biochemistry analysis measurements (mmol/L) of Sodium, Potassium, Chloride, Calcium, Phosphate . Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Incidence of clinically relevant changes (abnormalities) in laboratory parameters: haematology
Based on haematology analysis measurement haemoglobin (g/dL). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Clinically relevant changes in laboratory parameters: urinalysis
Based on urinalysis analysis measurements of the potential of hydrogen (pH). The pH scale is used to determine the degree of acidity of a substance. The basic pH scale extends from 0 (strong acid) to 7 (neutral, pure water) to 14 (strong caustic). Urine has the widest range of pH compared to other bodily fluids. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Clinically relevant changes in laboratory parameters: arterial blood gas
Based on arterial blood gas analysis measurements of Fraction of Inspired Oxygen (%). The fraction of inspired oxygen is the concentration or percentage of oxygen in the air that is inhaled by a person. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 12, and from day -1 to week 12
Clinically relevant changes in vital signs: blood pressure
Systolic and diastolic blood pressure (mmHg) will be measured after the patient has rested for at least 5 minutes in supine position (first measurement) and at least one minute after the first measurement (second measurement). Afterwards, systolic and diastolic blood pressure will be measured again in standing position after the patient has been standing for at least 3 minutes (third measurement). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Clinically relevant changes in vital signs: pulse rate
Pulse rate (bpm) will be measured after the patient has rested for at least 5 minutes in supine position (first measurement) and at least one minute after the first measurement (second measurement). Afterwards, vital signs will be measured again in standing position after the patient has been standing for at least 3 minutes (third measurement). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Clinically relevant changes in electrocardiogram ECG parameter QT interval
QT interval measures the time (msec) it takes the heart muscle to contract and then recover.
Baseline values will be obtained from V1/A1 of study BIA-51058-201. At Baseline of BIA-51058-201 study and week 12, triplicate 12-lead ECG will be recorded before IMP intake as well as 4 and 8 hours after IMP intake.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Clinically relevant changes in electrocardiogram ECG parameter QRS duration
The QRS duration measures the time (msec) required for a stimulus to spread through the heart ventricles (ventricular depolarization).
Baseline values will be obtained from V1/A1 of study BIA-51058-201. At Baseline of BIA-51058-201 study and week 12, triplicate 12-lead ECG will be recorded before IMP intake as well as 4 and 8 hours after IMP intake.
Measured: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Secondary outcomes (13)
Changes in haemodynamic parameters: pulmonary vascular resistance (PVR)
Pulmonary vascular resistance (measured in dyn*s/cm^5) is determined by right heart catheterization to be performed before IMP intake. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: right atrial pressure (RAP)
Right atrial pressure (RAP), measured in mmHg units, is a robust predictor of the pulmonary hypertension severity. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: mean pulmonary artery pressure (mPAP)
Haemodynamic parameter mean pulmonary artery pressure (mPAP) is measured in mmHg units. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: Cardiac index (CI)
Cardiac index (CI) is a haemodynamic parameter that relates the cardiac output from left ventricle in one minute to body surface area, thus relating heart performance to the size of the individual. The unit of measurement is liters per minute per square meter (L/min/m2). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: mixed venous oxygen saturation (SvO2)
SvO2 is the percentage (%) of oxygen bound to hemoglobin in blood returning to the right side of the heart. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From Baseline to week 12, and from Day -1 to week 12
Changes in the New York Heart Association / World Health Organization (NYHA/WHO) functional class
The NYHA/WHO Classification system is a tool that classifies patients with heart failure into one of four classes according to their degree of symptoms at rest and with activity: Class I, patients with pulmonary hypertension but without resulting limitation of physical activity; Class II, patients with pulmonary hypertension resulting in a slight limitation of physical activity; Class III, patients with pulmonary hypertension resulting in marked limitation of physical activity; Class IV: patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnoea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in the 6-minute walk test (6-MWT): Distance Covered
The 6-MWT is a self-paced test of walking capacity used to assess aerobic capacity and endurance. It plays a key role in evaluation functional exercise capacity, assessing prognosis and evaluating response to treatment across a wide range of respiratory diseases. The distance covered (m) over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in Biomarker N-terminal pro brain natriuretic peptide (NT-proBNP)
NT-proBNP levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure, as this marker is typically higher in patients with worse outcome. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in echocardiogram parameters
Parameters used include tricuspid regurgitation, right ventricular contractility, pericardial effusion, right atrial end-systolic area, right ventricular end-diastolic area. Tricuspid regurgitation is a type of heart valve disease in which the valve between the two right heart chambers doesn't close properly. As a result, blood leaks backward into the upper right chamber.
In was classified as absent, mild, moderate or severe. The right ventricle is the major determinant of functional state and prognosis in PAH. It was measured via tricuspid annular plane systolic excursion (TAPSE). A TAPSE value < 17 mm is considered to indicate right ventricular dysfunction. A pericardial effusion refers to the accumulation of fluid in the pericardial sac surrounding the heart. It was classified as absent (low risk), traces or present (high risk). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in Quality of life 36-item Short Form Health Survey version 2 (SF-36v2)
The SF-36v2 asks 36 questions (items) to measure the functional health and well-being from the patient's point of view. All 36 questions, except question 2 are used to score the 8 health domains. A total score was calculated for each health domain by taking the sum of the corresponding responses and rescaling it to a range of 0 to 100, where 100 represented the best possible result. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Measured: From baseline to week 6 and week 12, and from day -1 to week 12
Minimum Plasma Concentration (Cmin) of zamicastat and its metabolites (BIA 5-961 and BIA 5-453)
The pharmacokinetic (PK) parameter Minimum Plasma Concentration (Cmin) for zamicastat and its metabolites will be derived at the end of the dosing interval. Cmin will be measured in ng/mL units. Blood samples will be obtained prior to IMP intake.
Measured: Day -1, week 6 and week 12
Changes in plasma of dopamine ß-hydroxylase (DβH) activity
The assessment of plasma DβH activity (% inhibition) was performed centrally. Blood sampling for the assessment of plasma DβH activity was to be performed together with the PK blood sampling. Blood samples were to be taken prior to IMP intake. Baseline values will be obtained from V1/A1 of study BIA-51058-201. Day -1 visit
Measured: From baseline to week 6 and week 12, and from day -1 to week 12
Catecholamine (norepinephrine and dopamine) levels urinary pharmacodynamic change from baseline: changes in 24-hour
24-hour urine collection was to be started on the day before the respective visit. Results for norepinephrine and dopamine are given in nmol per 24 hours (nmol/24hr).
Measured: From baseline to week 6 and week 12, and from day -1 to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2023
- Study start26 Jun 2019
- Primary completion17 Feb 2022
- Study completion17 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bial - Portela C S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06009185
- Sponsor's protocol ID
- BIA-51058-202
- Other IDs
- 2018-002796-18, 2018
- Status last verified
- Aug 2023
- First submitted
- 17 Jul 2023
- Last updated
- 1 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015 Oct;46(4):903-75. doi: 10.1183/13993003.01032-2015. Epub 2015 Aug 29.
PubMed 26318161Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, McCormack MC, Carlin BW, Sciurba FC, Pitta F, Wanger J, MacIntyre N, Kaminsky DA, Culver BH, Revill SM, Hernandes NA, Andrianopoulos V, Camillo CA, Mitchell KE, Lee AL, Hill CJ, Singh SJ. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014 Dec;44(6):1428-46. doi: 10.1183/09031936.00150314. Epub 2014 Oct 30.
PubMed 25359355
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT06009185
- Acronym / sponsor ID
- BIA-51058-202
- Conditions
- Pulmonary Arterial Hypertension
- Keywords
- PAH, BIA 5-1058, Zamicastat, Bial, Bial - Portela & Ca, S.A., dopamine ß-hydroxylase (DßH) inhibitor, vascular obstruction, pulmonary arteries
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Bial - Portela C S.A.Industry (pharma, biotech, devices)
- Study start
- 26 Jun 2019 (actual)
- Primary completion
- 17 Feb 2022 (actual)
- Study completion
- 17 Feb 2022 (actual)
- First posted
- 24 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims 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 Pulmonary Arterial Hypertension (PAH) disease.
Detailed description
This is an extension study with Pulmonary Arterial Hypertension (PAH) patients who are under treatment with zamicastat as adjunctive therapy in the study BIA-51058-201.
For patients participating in this extension study, visit "Maintenance Period Visit 3" (MPV3) of the study BIA-51058-201 will also be the first visit (V1) of this extension study (BIA-51058-202). Their treatment with zamicastat will be continued at their individual highest tolerated dose (HTD) for an additional 12 weeks (50 mg, 100 mg, 150 mg or 200 mg).
Further visits will be performed 20 ±3 days (V2, telephone), 41 ±3 days (V3, on-site), 62 ±3 days (V4, telephone) and 83 ±3 days (V5, on-site) after V1. At V5, patients will have the opportunity to continue treatment with zamicastat in a compassionate use program. Patients who will not participate in this compassionate use program will come to the following follow-up visit(s):
- Follow-up (FU) down-titration (telephone, 14 ±2 days after V5); only applicable in patients taking 150 mg or 200 mg zamicastat
- FU visit (on-site, 14 ±2 days after last investigational medicinal product (IMP) intake).
The data and safety monitoring board (DSMB) will periodically review the safety data and will issue a recommendation if the study can be continued as planned.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HTD < 200 mg zamicastat | Experimental | Drug: Oral zamicastatTablets for oral administration under fed conditions. Zamicastat has to be taken in the morning after breakfast. Each patient will continue treatment with the individual highest tolerated dose (HTD) he/she was taking at MPV3 of the study BIA-51058-201 and will take this dose until visit V5. |
| HTD 200 mg zamicastat | Experimental | Drug: Oral zamicastatTablets for oral administration under fed conditions containing 100 mg of zamicastat (two tablets of 100 mg). Zamicastat has to be taken in the morning after breakfast. Each patient will continue treatment with the individual highest tolerated dose (HTD) he/she was taking at MPV3 of the study BIA-51058-201 and will take this dose until visit V5. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- For inclusion in the extension study, patients had to fulfil all of the following criteria at visit V1 (Day 1, start of the extension study):
- Have performed MPV3 of the preceding study BIA-51058-201.
- Able to comprehend and willing to sign an informed consent form (ICF).
- For women: Agreed not to donate ova from the time of informed consent until 30 days after the last IMP intake.
- For men: Agreed not to donate sperm from the time of informed consent until 90 days after the last IMP intake
Key exclusion criteria (17 listed)
- Significant non-compliance with the protocol during the preceding study BIA-51058-201 which may have an impact on this extension study.
- WHO functional class IV as judged by the investigator (reference 1)
- Two or more consecutive measurements of systolic blood pressure (SBP) < 95 mmHg or diastolic blood pressure (DBP) < 50 mmHg measured at visit V1.
- Uncontrolled diabetes mellitus with HbA1c ≥ 8.5% within the last three months or at visit V1.
- Occurrence of an AE during the preceding study which is judged by the investigator as contraindicative to further participation in the extension study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral zamicastatTablets for oral administration under fed conditions containing 100 mg of zamicastat. Zamicastat has to be taken in the morning after breakfast. | Drug | HTD 200 mg zamicastat, HTD < 200 mg zamicastat |
Primary outcome
Number of participants with adverse events (AEs)
Time frame: Up to 12 weeks
The number of participants with AEs will be presented. An AE is any untoward medical occurrence in a patient to whom a medicinal product is administered and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease occurring during the course of the study.
Clinically relevant changes in laboratory parameters: coagulation
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Based on coagulation analysis measurements of prothrombin time test (international normalized ratio). The prothrombin time (PT) test measures how long it takes for a clot to form in a blood sample. The International Normalized Ratio is a type of calculation based on PT test results. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Incidence of clinically relevant changes (abnormalities) in laboratory parameters: biochemistry
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Based on biochemistry analysis measurements (mmol/L) of Sodium, Potassium, Chloride, Calcium, Phosphate . Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Incidence of clinically relevant changes (abnormalities) in laboratory parameters: haematology
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Based on haematology analysis measurement haemoglobin (g/dL). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Clinically relevant changes in laboratory parameters: urinalysis
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Based on urinalysis analysis measurements of the potential of hydrogen (pH). The pH scale is used to determine the degree of acidity of a substance. The basic pH scale extends from 0 (strong acid) to 7 (neutral, pure water) to 14 (strong caustic). Urine has the widest range of pH compared to other bodily fluids. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Clinically relevant changes in laboratory parameters: arterial blood gas
Time frame: From baseline to week 12, and from day -1 to week 12
Based on arterial blood gas analysis measurements of Fraction of Inspired Oxygen (%). The fraction of inspired oxygen is the concentration or percentage of oxygen in the air that is inhaled by a person. Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Clinically relevant changes in vital signs: blood pressure
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Systolic and diastolic blood pressure (mmHg) will be measured after the patient has rested for at least 5 minutes in supine position (first measurement) and at least one minute after the first measurement (second measurement). Afterwards, systolic and diastolic blood pressure will be measured again in standing position after the patient has been standing for at least 3 minutes (third measurement). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Clinically relevant changes in vital signs: pulse rate
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
Pulse rate (bpm) will be measured after the patient has rested for at least 5 minutes in supine position (first measurement) and at least one minute after the first measurement (second measurement). Afterwards, vital signs will be measured again in standing position after the patient has been standing for at least 3 minutes (third measurement). Baseline values will be obtained from V1/A1 of study BIA-51058-201.
Clinically relevant changes in electrocardiogram ECG parameter QT interval
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
QT interval measures the time (msec) it takes the heart muscle to contract and then recover. Baseline values will be obtained from V1/A1 of study BIA-51058-201. At Baseline of BIA-51058-201 study and week 12, triplicate 12-lead ECG will be recorded before IMP intake as well as 4 and 8 hours after IMP intake.
Clinically relevant changes in electrocardiogram ECG parameter QRS duration
Time frame: From baseline to week 6 and week 12, and from day -1 to week 6 and week 12
The QRS duration measures the time (msec) required for a stimulus to spread through the heart ventricles (ventricular depolarization). Baseline values will be obtained from V1/A1 of study BIA-51058-201. At Baseline of BIA-51058-201 study and week 12, triplicate 12-lead ECG will be recorded before IMP intake as well as 4 and 8 hours after IMP intake.
13 secondary outcomes
Changes in haemodynamic parameters: pulmonary vascular resistance (PVR)
Time frame: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: right atrial pressure (RAP)
Time frame: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: mean pulmonary artery pressure (mPAP)
Time frame: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: Cardiac index (CI)
Time frame: From Baseline to week 12, and from Day -1 to week 12
Changes in haemodynamic parameters: mixed venous oxygen saturation (SvO2)
Time frame: From Baseline to week 12, and from Day -1 to week 12
Changes in the New York Heart Association / World Health Organization (NYHA/WHO) functional class
Time frame: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in the 6-minute walk test (6-MWT): Distance Covered
Time frame: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in Biomarker N-terminal pro brain natriuretic peptide (NT-proBNP)
Time frame: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in echocardiogram parameters
Time frame: From baseline to week 6 and week 12, and from day -1 to week 12
Changes in Quality of life 36-item Short Form Health Survey version 2 (SF-36v2)
Time frame: From baseline to week 6 and week 12, and from day -1 to week 12
Minimum Plasma Concentration (Cmin) of zamicastat and its metabolites (BIA 5-961 and BIA 5-453)
Time frame: Day -1, week 6 and week 12
Changes in plasma of dopamine ß-hydroxylase (DβH) activity
Time frame: From baseline to week 6 and week 12, and from day -1 to week 12
Catecholamine (norepinephrine and dopamine) levels urinary pharmacodynamic change from baseline: changes in 24-hour
Time frame: From baseline to week 6 and week 12, and from day -1 to week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
- Background: PubMed 26318161Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015 Oct;46(4):903-75. doi: 10.1183/13993003.01032-2015. Epub 2015 Aug 29.
- Background: PubMed 25359355Holland AE, Spruit MA, Troosters T, Puhan MA, Pepin V, Saey D, McCormack MC, Carlin BW, Sciurba FC, Pitta F, Wanger J, MacIntyre N, Kaminsky DA, Culver BH, Revill SM, Hernandes NA, Andrianopoulos V, Camillo CA, Mitchell KE, Lee AL, Hill CJ, Singh SJ. An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease. Eur Respir J. 2014 Dec;44(6):1428-46. doi: 10.1183/09031936.00150314. Epub 2014 Oct 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral zamicastat in people with Pulmonary Arterial Hypertension, run by Bial - Portela C S.A. at 11 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Spain, Italy, United Kingdom, Austria, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (AEs) (time frame: Up to 12 weeks). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06009185, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2023.