- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05343637
A Dose Escalation Study to Evaluate the Effect of RT234 in Subjects With Pulmonary Arterial Hypertension
A Phase 2a, Dose Escalation Study to Evaluate the Effect of RT234 on Cardiopulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension
This multicenter, open label, Phase 2a study is designed to evaluate the effect of inhaled RT234 delivered in a dose escalation manner on the change in pulmonary vascular resistance (PVR) in subjects with Pulmonary Arterial Hypertension (PAH) undergoing Right heart catheterization (RHC).
This study is also known as Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2a (VIPAH-PRN 2a) study
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New South Wales
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Darlinghurst, New South Wales, Australia, 2010
- St Vincent's Hospital
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Tasmania
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Hobart, Tasmania, Australia, 7000
- Royal Hobart Hospital
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Victoria
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Melbourne, Victoria, Australia, 3004
- The Alfred Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Between 18 and 80 years of age, inclusive.
Diagnosis of RHC-confirmed WHO Group 1 PAH in any of the following three categories: Idiopathic, primary or familial pulmonary arterial hypertension (IPAH, PPH, or FPAH); OR PAH associated with one of the following connective tissue diseases (CTD):
- Systemic sclerosis (scleroderma)
- Limited scleroderma
- Mixed connective tissue disease
- Systemic lupus erythematosus
- Overlap syndrome
- Other autoimmune disorders;
OR PAH associated with:
- Human immunodeficiency virus (HIV) infection with no evidence of opportunistic infection in the preceding 6 months;
- Simple, congenital systemic-to-pulmonary shunts at least one-year post-surgical repair.
- Exposure to legal drugs, chemicals and toxins, such as fenfluramine, derivatives, other anorexigens, toxic rapeseed oil or L-tryptophan. Subjects with PAH associated with illegal drug use, such as methamphetamine, were excluded.
Previous diagnosis with PAH with the following conditions:
- Stable PAH without significant adjustments of disease-specific background PAH therapy, at least 3 months prior to RHC procedure;
- If on corticosteroids, has been receiving a stable dose of ≤ 20 mg/day of prednisone (or equivalent dose of other corticosteroid) for at least 30 days prior to RHC procedure.
Pulmonary Function Tests within 24 months prior to RHC procedure that fulfilled the following criteria (pulmonary function; (PFT may be assessed at Screening if historical PFT results are not available):
- Forced Expiratory volume in one second (FEV1) ≥ 60% predicted (pre-bronchodilators);
- FEV1/ forced expiratory vital capacity (FVC) ≥ 60% (pre-bronchodilators);
- FVC ≥ 60% predicted.
Exclusion Criteria:
- Baseline systemic hypotension, defined as MAP < 50 mmHg or systolic blood pressure (SBP)< 90 mmHg at Screening.
- Requirement of intravenous inotropes within 30 days prior to RHC procedure.
- Use of oral, topical or inhaled nitrates within 14 days prior to RHC procedure.
- Uncontrolled systemic hypertension: SBP > 160 mmHg or diastolic blood pressure (DBP) >100 mmHg at Screening.
- 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).
- Chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL at Screening or requires dialysis.
- History of atrial septostomy.
- Unrepaired congenital heart disease (CHD).
- Pericardial constriction; restrictive or congestive cardiomyopathy.
- History of left ventricular ejection fraction (EF) < 40% by multiple gated acquisition scan (MUGA), angiography, echocardiography, or cardiac magnetic resonance imaging (CMRI).
- Symptomatic coronary disease with demonstrable ischemia.
- Poorly controlled asthma defined by active wheezing and/or cough at the time of Screening or day of participation in Parts A and B.
- Clinically significant intercurrent illness (including lower respiratory tract infection) or clinically significant surgery within 30 days prior to study drug administration.
- Clinical RHC < 14 days prior to Screening.
- History of non-arteritic anterior ischemic optic neuropathy (NAION) or retinitis pigmentosa.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: RT234 - Cohort 1
Participants will receive RT234 as 0.2 mg and 0.6 mg
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RT234 is a drug/device combination product composed of vardenafil hydrochloride as the drug constituent and will utilize RS01 DPI device.
Other Names:
|
EXPERIMENTAL: RT234 - Cohort 2
Participants will receive RT234 as 0.6 mg and 1.2 mg
|
RT234 is a drug/device combination product composed of vardenafil hydrochloride as the drug constituent and will utilize RS01 DPI device.
Other Names:
|
EXPERIMENTAL: RT234 - Cohort 3
Participants will receive RT234 as 1.2 mg and 2.4 mg
|
RT234 is a drug/device combination product composed of vardenafil hydrochloride as the drug constituent and will utilize RS01 DPI device.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation of adverse events (AEs)
Time Frame: Screening to Day 30
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Evaluation of AEs will be measured by clinical examination and participant self-reporting.
Known or possible adverse events include headache, lightheadedness and cough.
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Screening to Day 30
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Peak plasma concentration (Cmax)
Time Frame: 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.
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Change in Cmax at each dose level on Day 1.
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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.
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Time to peak plasma concentration (Tmax)
Time Frame: 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.
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Change in Tmax at each dose level on Day 1.
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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.
|
Area under the plasma concentration versus time curve (AUC)
Time Frame: 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.
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Change in AUC at each dose level on Day 1.
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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.
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Terminal half-life
Time Frame: 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.
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Change in terminal half-life at each dose level on Day 1.
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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.
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Change in pulmonary vascular resistance (PVR)
Time Frame: 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.
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Maximal change from baseline in PVR assessed at the time by right heart catheterisation (RHC).
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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.
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Carol Ann Satler, MD, PhD, Respira Therapeutics
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Respiratory Tract Diseases
- Vascular Diseases
- Cardiovascular Diseases
- Lung Diseases
- Pulmonary Arterial Hypertension
- Enzyme Inhibitors
- Vasodilator Agents
- Molecular Mechanisms of Pharmacological Action
- Hypertension, Pulmonary
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Familial Primary Pulmonary Hypertension
- Vardenafil Dihydrochloride
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Hypertension, Pulmonary
- Hypertension
- Pulmonary Arterial Hypertension
- Familial Primary Pulmonary Hypertension
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Vardenafil Dihydrochloride
Other Study ID Numbers
- RT234-CL201
- ACTRN12619001178134 (REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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