To identify the effective dose(s) of RT234 (vardenafil inhalation powder) to acutely improve pulmonary vascular haemodynamics in study participants with Pulmonary Arterial Hypertension (PAH).
- Conditions
- Pulmonary Arterial HypertensionCardiovascular - Other cardiovascular diseases
- Registration Number
- ACTRN12619001178134
- Lead Sponsor
- Respira Therapeutics Australia Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 14
1. Diagnosis of RHC-confirmed WHO Group 1 PAH in any of the following three categories:
a) Idiopathic, primary or familial pulmonary arterial hypertension (IPAH, PPH, or FPAH);
OR
b) PAH associated with one of the following connective tissue diseases (CTD):
i) Systemic sclerosis (scleroderma)
ii) Limited scleroderma
iii) Mixed connective tissue disease
iv) Systemic lupus erythematosus
v) Overlap syndrome;
OR
c) PAH associated with:
i) Human immunodeficiency virus (HIV) infection with no evidence of opportunistic infection in the preceding 6 months;
ii) Simple, congenital systemic-to-pulmonary shunts at least one-year post-surgical repair.
iii) Exposure to legal drugs, chemicals and toxins, such as fenfluramine, derivatives, other anorexigens, toxic rapeseed oil or L-tryptophan.
2. Previously diagnosed with PAH but with the following conditions:
a) Stable PAH without significant adjustments of disease-specific background PAH therapy, at least 3 months prior to RHC procedure;
b) If on corticosteroids, has been receiving a stable dose of less than or equal to 20 mg/day of prednisone (or equivalent dose of other corticosteroid) for at least 30 days prior to RHC procedure.
3. Pulmonary Function Tests (PFT) within 24 months prior to RHC procedure that fulfill the following criteria:
a) Forced Expiratory volume in one second (FEV1) greater than or equal to 70% predicted (pre-bronchodilators);
b) FEV1/forced expiratory vital capacity (FVC) greater than or equal to 70% and less than or equal to 90% (pre-bronchodilators);
c) FVC greater than or equal to 70% predicted.
4. Females of childbearing potential must have a negative pregnancy test at Screening, Day 1 and Day 15
5. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual periods for at least 12 months) or have documented evidence of surgical sterilization at least 6 months prior to Screening.
1. Baseline systemic hypotension, defined as MAP <50 mmHg or systolic blood pressure (SBP) <90 mmHg at Screening
2. Requirement of intravenous inotropes within 30 days prior to RHC procedure
3. Use of oral, topical or inhaled nitrates within 2 weeks prior to RHC procedure
4. Uncontrolled systemic hypertension: SBP >160 mmHg or diastolic blood pressure (DBP) >100 mmHg during Screening
5. History of portal hypertension or chronic liver disease, including active viral replication of hepatitis B and/or hepatitis C, or classified as having moderate to severe hepatic impairment (Child-Pugh Class B-C)
6. Chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at Screening or requires dialysis
7. History of atrial septostomy
8. Unrepaired congenital heart disease
9. Pericardial constriction; restrictive or congestive cardiomyopathy
10. History of left ventricular ejection fraction (EF) < 40%
11. Symptomatic coronary disease with demonstrable ischemia
12. Poorly controlled asthma
13. Clinically significant intercurrent illness or surgery within 30 days of Day 1
14. Known or suspected hypersensitivity or allergic reaction to vardenafil
Clinical RHC <2 weeks from Screening
15. History of non-arteritic anterior ischemic optic neuropathy (NAION) or retinitis pigmentosa
16. QTcF) >450 msec on an electrocardiogram (ECG) at Screening.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Evaluation of adverse events (AEs) will be measured by clinical examination and participant self-reporting. Known or possible adverse events include headache, lightheadedness and cough.[Screening to Day 30.<br><br>];Change in baseline plasma Pharmacokinetic (PK) measures (Cmax, Tmax, AUC, terminal half-life) of drug exposure at each dose level on Day 1.[At baseline, 5, 15, 30, 45 and 60 minutes post-end of inhalation for the first RT234 dose and at 5, 15, 30, 45, 60, 75, 90, 105 and 120 minutes post-end of inhalation for the second RT234 dose. ];Maximal change from baseline in pulmonary vascular resistance (PVR) assessed at the time by right heart catheterisation (RHC).[At baseline, 5, 15, 30, 45 and 60 minutes post-end of inhalation for the first RT234 dose and at 5, 15, 30, 45, 60, 75, 90, 105 and 120 minutes post-end of inhalation for the second RT234 dose on Day 1.]
- Secondary Outcome Measures
Name Time Method