Study to evaluate the safety, tolerability and efficacy of AZD4831 in thetreatment of patients with pulmonary hypertensio

Phase 1

• Conditions: Group 1: Pulmonary arterial hypertension (PAH)Group 2: Postcapillary pulmonary hypertension; MedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; MedDRA version: 21.1Level: PTClassification code 10037400Term: Pulmonary hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2020-002788-80-DE
• Lead Sponsor: niversity of Cologne

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-06-08
• Last Update Posted: 21 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1. Signed written informed consent form
2. Capability and willingness to comply with study procedures
3. Adult patients age 18–85 years (male and female)
4. Females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of non-child-bearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:
a) Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
5. Male patients must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of AZD4831/matching placebo to prevent pregnancy in a partner. Male patients must not donate or bank sperm during this same time
6. WHO Group 1 diagnosis of IPAH; HPAH; or PAH associated with connective tissue disease (CTD), drugs/toxins, HIV, repaired congenital heart defect (CHD) OR WHO group 2 diagnosis of postcapillary PH
7. On stable therapy (=1 approved drug) before inclusion (signed ICF) for =12 weeks, =8 weeks at same dose
8. Symptomatic despite therapy (WHO functional class II or III)
9. 6MWD =100 m at screening
10. Hemodynamic criteria:
Group 1:
• mPAP =25 mmHg
• PAWP or LVEDP = 15 mmHg
• PVR > 3 Wood units
Group 2:
• mPAP =25 mmHg
• PAWP or LVEDP > 15 mmHg
• Irrespective of PVR
11. No chronic thromboembolic pulmonary hypertension (CTEPH) as
documented by a negative or low probability lung ventilation/perfusion scan or negative pulmonary arteriogram
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 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Only for the group 1) : PAH associated with significant venous or capillary involvement (PCWP >15 mmHg), pulmonary capillary hemangiomatosis, portal hypertension or unrepaired CHD
2. Pulmonary hypertension belonging to WHO Groups 3–5
3. Uncontrolled hypertension (=160/100 mmHg), at least one value is increased
4. Moderate stage renal disease for patients treated with AZD4831 (eGFR <30ml/min)
5. Severe liver disease (Child-Pugh class C, with or without cirrhosis); elevation of liver enzymes (AST/ALT) to > 3x ULN
6. Hypersensitivity to the active substance or one of the ingredients (see current IB)
7. Participation in another interventional clinical study within 30 days before baseline
8. Any clinically significant disease or disorder (e.g. cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, infectious disease or major physical impairment) which, as judged by the Investigator, might put the patient at risk because of participation in the study, or probable alternative primary reason for patient's symptoms in judgment of Investigator.
9. Current or previous (within past 12 months) systemic fungal infection, prior screening
10. Patients with uncontrolled or clinically significant thyroid disease as judged by the investigator
11. Any ongoing skin disorder, history of or ongoing clinically significant allergy/hypersensitivity
12. Drug or alcohol abuse, either current or within previous 12 months
13. Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
14. Intake of strong inhibitors of CYP3A4 (i.e. itraconazole and clarithromycin) or inducers of CYP3A4 (phenytoin and rifampicin)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified