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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05343637




Registration number
NCT05343637
Ethics application status
Date submitted
4/04/2022
Date registered
25/04/2022
Date last updated
25/04/2022

Titles & IDs
Public title
A Dose Escalation Study to Evaluate the Effect of RT234 in Subjects With Pulmonary Arterial Hypertension
Scientific title
A Phase 2a, Dose Escalation Study to Evaluate the Effect of RT234 on Cardiopulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension
Secondary ID [1] 0 0
ACTRN12619001178134
Secondary ID [2] 0 0
RT234-CL201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combination Product - Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)

Experimental: RT234 - Cohort 1 - Participants will receive RT234 as 0.2 mg and 0.6 mg

Experimental: RT234 - Cohort 2 - Participants will receive RT234 as 0.6 mg and 1.2 mg

Experimental: RT234 - Cohort 3 - Participants will receive RT234 as 1.2 mg and 2.4 mg


Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)
RT234 is a drug/device combination product composed of vardenafil hydrochloride as the drug constituent and will utilize RS01 DPI device.
Intervention code [1] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Evaluation of adverse events (AEs)
Timepoint [1] 0 0
Screening to Day 30
Primary outcome [2] 0 0
Peak plasma concentration (Cmax)
Timepoint [2] 0 0
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.
Primary outcome [3] 0 0
Time to peak plasma concentration (Tmax)
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Area under the plasma concentration versus time curve (AUC)
Timepoint [4] 0 0
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.
Primary outcome [5] 0 0
Terminal half-life
Timepoint [5] 0 0
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.
Primary outcome [6] 0 0
Change in pulmonary vascular resistance (PVR)
Timepoint [6] 0 0
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.

Eligibility
Key inclusion criteria
1. Between 18 and 80 years of age, inclusive.

2. 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):

1. Systemic sclerosis (scleroderma)

2. Limited scleroderma

3. Mixed connective tissue disease

4. Systemic lupus erythematosus

5. Overlap syndrome

6. Other autoimmune disorders;

OR PAH associated with:

1. Human immunodeficiency virus (HIV) infection with no evidence of opportunistic
infection in the preceding 6 months;

2. Simple, congenital systemic-to-pulmonary shunts at least one-year post-surgical
repair.

3. 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.

3. Previous diagnosis with PAH with the following conditions:

1. Stable PAH without significant adjustments of disease-specific background PAH
therapy, at least 3 months prior to RHC procedure;

2. 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.

4. 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):

1. Forced Expiratory volume in one second (FEV1) = 60% predicted
(pre-bronchodilators);

2. FEV1/ forced expiratory vital capacity (FVC) = 60% (pre-bronchodilators);

3. FVC = 60% predicted.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 14 days prior to RHC procedure.

4. Uncontrolled systemic hypertension: SBP > 160 mmHg or diastolic blood pressure (DBP)
>100 mmHg at 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 (CHD).

9. Pericardial constriction; restrictive or congestive cardiomyopathy.

10. History of left ventricular ejection fraction (EF) < 40% by multiple gated acquisition
scan (MUGA), angiography, echocardiography, or cardiac magnetic resonance imaging
(CMRI).

11. Symptomatic coronary disease with demonstrable ischemia.

12. Poorly controlled asthma defined by active wheezing and/or cough at the time of
Screening or day of participation in Parts A and B.

13. Clinically significant intercurrent illness (including lower respiratory tract
infection) or clinically significant surgery within 30 days prior to study drug
administration.

14. Clinical RHC < 14 days prior to Screening.

15. History of non-arteritic anterior ischemic optic neuropathy (NAION) or retinitis
pigmentosa.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/07/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/01/2020
Sample size
Target
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
7000 - Hobart
Recruitment postcode(s) [3] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Respira Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT05343637
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Carol Ann Satler, MD, PhD
Address 0 0
Respira Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries