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Pulmonary Arterial HypertensionPhase 2VIPAH-PRN_2BNCT04266197

Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2B Study

A Phase 2 study testing Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI) in people with Pulmonary Arterial Hypertension, run by Respira Therapeutics, Inc. at 26 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The objectives of this study are to evaluate the safety of RT234 and the effects of RT234 on exercise capacity as assessed by Cardiopulmonary Exercise Testing (CPET) and six minute walk testing (6MWT) as well as exertional symptoms in patients with pulmonary arterial hypertension (PAH). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
26 sitesUnited States
Study dates
25 Sep 2020to 7 Jan 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must be between 18 and 80 years of age, inclusive.
  • Must be willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to undergoing any research-related procedures.
  • Must be willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Able to exercise during CPET and ambulate independently.
  • Diagnosis documented and confirmed by Right Heart Catheterization (RHC)-confirmed WHO Group 1 PAH in any of the following 3 categories:
  • Idiopathic, primary, or familial pulmonary arterial hypertension (IPAH, PPH, or FPAH) OR
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  • PAH associated with one of the following connective tissue diseases:
  • Systemic sclerosis (scleroderma) ii) Limited scleroderma iii) Mixed connective tissue disease iv) Systemic lupus erythematosus v) Overlap syndrome vi) Other autoimmune disorders OR c) PAH associated with: i) Human immunodeficiency virus (HIV) infection. ii) Simple, congenital systemic-to-pulmonary shunts at least 1-year post-surgical repair.
  • Exposure to drugs, chemicals, and toxins, such as fenfluramine derivatives, other anorexigens, toxic rapeseed oil, or L-tryptophan.
  • Subjects with a diagnosis of HIV must have stable disease, defined by:
  • Unchanged medication treatment regimen for HIV for at least 8 weeks prior to beginning Visit 1 Screen assessments.
  • No active opportunistic infection during the Screening Period.
  • No hospitalizations for HIV for at least 4 weeks prior to beginning Visit 1 Screen assessments.
  • The patient must have adequate, documented test results that exclude chronic thromboembolic pulmonary hypertension (CTEPH).
  • Previous diagnosis of PAH, but with the following conditions:
  • Stable PAH without significant adjustments of disease-specific background PAH therapy, at least 3 months prior to the Baseline CPET procedure. Stable is defined as no change in PAH -specific drug therapy within 3 months of Screening Visit 1, and for the duration of the study, and no change in dose of PAH-specific drug(s) within 1 month of Screening.
  • AND
  • 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 the Baseline CPET.
  • PFT within 6 months prior to signing the Informed Consent Form that fulfills the following criteria:
  • FEV1 ≥ 60% predicted (pre-bronchodilators).
  • FEV1 / FVC ≥ 60% (pre-bronchodilators).
  • FVC ≥ 60% predicted.
  • Has had RHC performed and documented prior to Screening that meets the following hemodynamic criteria:
  • mPAP ≥ 20 mmHg.
  • PVR ≥ 300 dyn·s/cm5.
  • PCWP or LVEDP of ≤ 12 mmHg if PVR ≥ 300 to \< 500 dyn∙s/cm5, or PCWP or LVEDP ≤ 15 mmHg if PVR ≥ 500 dyn∙s/cm5.
  • Has WHO/New York Heart Association (WHO/NYHA) functional class II-IV symptomatology.
  • On stable oral PAH disease-specific background therapy of oral or inhaled therapies (any combination of an endothelin receptor antagonist, phosphodiesterase type 5 inhibitor, and/or a prostacyclin or prostacyclin receptor agonist). Stable is defined as no change in PAH-specific drug therapy within 3 months of Screening Visit 1, and for the duration of the study, and no change in dose of PAH-specific drug(s) within 1 month of Screening. Parenteral prostacyclin subjects will be limited to up to 20% of a particular cohort with approval of Sponsor Medical Monitor. Sotatercept subjects should have been on sotatercept for a minimum of 6 months at the time of screening. Sotatercept subjects will be limited to 20% of a particular cohort with approval of the Sponsor Medical Monitor.
  • Must be able to walk a distance of ≥ 150 meters in the Baseline 6MWTs. This will be determined using the mean of the two 6MWT results done during Screening. If tolerable by the subject, the 2 Baseline 6MWTs will be conducted at Visit 1 with a minimum of 2 hours of rest between the first and second tests.
  • Has a VE/VCO2 slope ≥ 36 during the Baseline CPET as assessed by the study CPET Core Laboratory.
  • Evidence of good effort on the Baseline CPET reaching a peak RER \> 1.0 as assessed by the study CPET Core Laboratory.
  • Peak VO2 ≤ 20 ml/min/kg during the Baseline CPET as assessed by the study CPET Core Laboratory.
  • If the subject is taking the following concomitant medications which may affect PAH, the subject must be on a stable therapeutic dose for at least 1 month prior to the start of Screening and the dosage maintained throughout the study.
  • Vasodilators (including calcium channel blockers - specify the indication e.g., PAH, hypertension, Raynaud's disease), digoxin, or L-arginine supplement.
  • If the subject is taking a vitamin K antagonist anticoagulant, then anticoagulation status should be maintained/stable in the therapeutic range for at least 1 month before the start of Screening.
  • Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study through the 30-day post-treatment safety follow-up telephone call. Acceptable methods of contraception include hormonal birth control (oral, intravaginal, transdermal, implantable, or intrauterine device/system [IUD/IUS]), IUDs (non-hormonal), vasectomy (in male partner), or any double-barrier methods (combination of male condom and spermicide with either cap, diaphragm, or sponge).
  • Female subjects of childbearing potential must have a negative pregnancy test (urine or serum) at Screening and must agree to additional urine pregnancy tests prior to each dose of study medication while participating in the study.
  • Female subjects considered not of childbearing potential include those who are post-menopausal (defined as cessation of regular menstrual periods for at least 1 year) or have documented evidence of surgical sterilization at least 6 months prior to Screening.
  • No evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically, by polymerase chain reaction (PCR) test, or antigen test as required by local site infection control policies at the Screening Visit. Subjects with previous coronavirus disease 2019 (COVID-19) infection must have returned to functional baseline prior to entering Screening for this study.

Who cannot join

  • Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
  • Baseline systemic hypotension defined as mean arterial pressure (MAP) \< 50 mmHg or SBP \< 90 mmHg at Screening.
  • History of chronic uncontrolled asthma; subjects with inability to use, or may have potential difficulties using, an inhaler device.
  • Use of continuous, supplemental oxygen. Subject must be able to complete exercise tests without the use of supplemental oxygen.
  • NOTE: Use of nocturnal oxygen is acceptable.
  • Requirement of intravenous inotropic therapies within 30 days prior to the Baseline CPET procedure.
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  • Use of riociguat (Adempas®) as background PAH therapy as of 1 month prior to initiating Screening or during the study through the end of Visit 4.
  • Use of oral, topical, or inhaled nitrates within 2 weeks prior to the Baseline CPET procedure.
  • Has history of uncontrolled systemic hypertension as evidenced by sitting SBP \> 175 mmHg or sitting diastolic blood pressure (DBP) \> 110 mmHg at Screening.
  • Portopulmonary hypertension, portal hypertension, or chronic liver disease determined to be Child-Pugh B or C, including hepatitis B virus and/or hepatitis C virus (HCV). Subjects who have had a previous infection with HCV and who have a negative viral load after receiving a course of curative treatment are
  • Subjects who have 3 or more of the following left ventricular disease/dysfunction risk factors are not eligible:
  • Hypertension requiring medication therapy.
  • Diabetes mellitus - any type.
  • History of significant coronary artery disease (CAD) established by any one of the following:
  • Myocardial infarction within 12 months of screening ii) Percutaneous coronary intervention within 12 months of screening iii) Angiographic evidence of CAD (\> 50% stenosis in at least 1 vessel) either by invasive angiography or by CT angiography.
  • Positive stress test imaging, either pharmacologic or with exercise. v) Previous coronary artery surgery. vi) Chronic stable angina.
  • Uncorrected right-to-left shunt, clinically relevant persistently patent foramen ovale in the judgement of the Investigator or known Eisenmenger's physiology.
  • Paroxysmal or uncontrolled atrial fibrillation (defined as a resting heart rate greater than or equal to 110 bpm).
  • Chronic renal insufficiency as defined by serum creatinine \> 2.5 mg/dL or has an estimated glomerular filtration rate (eGFR) \< 30 mL/min utilizing the Modification of Diet in Renal Disease (MDRD) Study equation at Screening or requires dialytic support.
  • Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is ≥ 3x the upper limit of the normal range.
  • Platelets below 50,000/μL at Screening.
  • Hemoglobin (Hgb) concentration \< 9 g/dL at Screening.
  • Malignancy within 2 years prior to Screening with the exception of localized non-metastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix excised with curative intent.
  • Recent history (within 6 months prior to Screening) of, or current alcohol or drug/solvent use disorder as assessed by the Investigator.
  • Known hypersensitivity to active drug substance (vardenafil) or drugs of the same class, or any excipients of the drug formulation(s).
  • Documented history of hypotension including fainting, syncope, orthostatic hypotension, and/or vasovagal reactions.
  • Vision loss due to non-arteritic anterior ischemic optic neuropathy or other optic perfusion impairment.
  • History of sudden sensorineural hearing loss.
  • Male subjects with a corrected QT interval using Fridericia's formula (QTcF) \> 450 msec and female subjects with QTcF \> 470 msec on ECG measured at Screening. (Correction of the actual QTc for the conduction defect of left bundle-branch can be made by subtracting the prolongation of the QRS due to the block from the actual QTc. Correction for the right bundle-branch block can be made by subtracting 20 msec from the actual QTc).
  • Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time while participating in the study.
  • Participation in a drug, device, or other interventional clinical study, other than a post-marketing observational extension study, within 30 days prior to Screening.
  • Enrolled in an exercise training program within 12 weeks prior to beginning Visit 1 Screening assessments and must agree not to enroll in an exercise training program during the study. Subjects enrolled in an exercise program more than 12 weeks prior to beginning Visit 1 Screening assessments may be enrolled if they agree to maintain their current level of physical activity throughout the duration of the study.
  • Has a concurrent disease or condition that in the view of the Principal Investigator, places the potential subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or would affect safety.
  • Has received the SARS-CoV-2 vaccine or booster within 1 week prior to Screening
  • Post COVID-19 chronic symptoms ("Long COVID") at Screening. NOTE: Investigators, study staff, or their immediate family members may not participate in the study.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

United States26 sites

  • University of New Mexico

    Albuquerque, New Mexico, 87131

  • Augusta University

    Augusta, Georgia, 30912

  • Ascension Seton Medical Center Austin

    Austin, Texas, 78705

  • University of Alabama

    Birmingham, Alabama, 35294

  • Tufts University

    Boston, Massachusetts, 02111

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University Hospital

    Cleveland, Ohio, 44106

  • The Ohio State University

    Columbus, Ohio, 43210

  • Baylor Scott and White Institute

    Dallas, Texas, 75246

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • The University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • UCLA

    Los Angeles, California, 90024

  • University of Southern California

    Los Angeles, California, 90033

  • Norton Health

    Louisville, Kentucky, 40202

  • Aurora St. Luke's Medical Center

    Milwaukee, Wisconsin, 53215

  • Mount Sinai Hospital

    New York, New York, 10029

  • Virginia Commonwealth University

    Richmond, Virginia, 23284

  • Mayo Clinic

    Rochester, Minnesota, 20010

  • UC Davis

    Sacramento, California, 95618

  • University of California San Francisco

    San Francisco, California, 94143

  • Ochsner Louisiana State University Health

    Shreveport, Louisiana, 71103

  • Washington University

    St Louis, Missouri, 63110

  • The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Torrance, California, 90502

  • University of Arizona

    Tucson, Arizona, 85724

  • MedStar Heart and Vascular Institute

    Washington D.C., District of Columbia, 20010

Other trials in United States

About this study

Official title: A Phase 2b, Open-label, Single Dose Study to Evaluate the Safety and Efficacy of RT234 on Exercise Parameters Assessed by Cardiopulmonary Exercise Testing (CPET) in Subjects With Pulmonary Arterial Hypertension (PAH)

The objectives of this study are to evaluate the safety of RT234 and the effects of RT234 on exercise capacity as assessed by Cardiopulmonary Exercise Testing (CPET) and six minute walk testing (6MWT) as well as exertional symptoms in patients with pulmonary arterial hypertension (PAH).

Read the detailed description

PAH results in significant limitations in cardiorespiratory fitness (CRF), exercise capacity, and profound dyspnea with physical exertion. The objective of this study is to assess the ability of a single inhaled dose of RT234 to acutely improve primary CPET measures of CRF and exercise capacity, and to decrease the experience of lower the sensation of dyspnea with physical exertion compared to baseline CPET measures.

Being tested
Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
Keywords
Cardiopulmonary Exercise Test, 6MWT
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.

  • Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)Combination product

    Also called inhaled vardenafil

    RT234 capsules of a dry powder formulation containing vardenafil administered via oral inhalation with a non-invasive AOS DPI.

Study groups in NCT04266197
Study groupRoleWhat they receive
RT234 0.5 mg Cohort 1ExperimentalRT234 at a capsule dose strength of 0.5 mg.
Receives: Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
RT234 1.0 mg Cohort 2ExperimentalRT234 at a capsule dose strength of 1.0 mg.
Receives: Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
RT234 2.0 mg Cohort 3ExperimentalRT234 at a capsule dose strength of 2.0 mg.
Receives: Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change in Peak Oxygen Uptake at Peak Exercise During CPET (Peak VO2)

    The primary efficacy endpoint was the change from Baseline in peak V̇ O2 measured during CPET after RT234 dosing.

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

  2. Median Change in Peak Oxygen Uptake at Peak Exercise During CPET (Peak VO2)

    The primary efficacy endpoint was the change from Baseline in peak V̇ O2 measured during CPET after RT234 dosing.

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

Secondary outcomes (7)

  1. Mean Change in Ventilatory Efficiency up to Peak Exercise During CPET

    Change from Baseline to postdose in the V̇E/V̇CO2 slope, a recognized measure of ventilatory efficiency, measured up to peak during CPET. VE/VCO2 tracks the ratio between total air breathed in per minute (VE) and the amount of carbon dioxide exhaled (VCO2) during a cardiopulmonary exercise test (CPET). A reduction in the ratio is favorable, as it indicates that less breathed air is required to clear out the same amount of CO2.

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

  2. Median Change in Ventilatory Efficiency up to Peak Exercise During CPET

    Change from Baseline to postdose in the V̇E/V̇CO2 slope, a recognized measure of ventilatory efficiency, measured up to peak during CPET. VE/VCO2 tracks the ratio between total air breathed in per minute (VE) and the amount of carbon dioxide exhaled (VCO2) during a cardiopulmonary exercise test (CPET). A reduction in the ratio is favorable, as it indicates that less breathed air is required to clear out the same amount of CO2.

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

  3. Change in Perceived Dyspnea at Peak Exercise During CPET

    Self-reported by subjects. Change in perceived dyspnea at peak exercise during CPET as assessed by the Modified Borg Dyspnea Scale Score. (Minimum score: 0 representing no dyspnea; maximum score: 10 representing maximal dyspnea; a reduction in score represents a favorable outcome.)

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

  4. Change in Perceived Exertion at Peak Exercise During CPET

    Self-reported by subjects. Change in perceived exertion at peak exercise during CPET as assessed by the Borg Rating of Perceived Exertion (RPE) Scale score, which rates exertion from a scale of 6 (no exertion) to 20 (maximum effort). A decrease in score is favorable.

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

  5. Change in Partial Pressure of End-tidal CO2 (PETCO2)

    Change in partial pressure of end-tidal CO2 (PETCO2) apex response to exercise, i.e., highest level during CPET

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

  6. Change in Ramp-incremental Duration of CPET

    Measured: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart

  7. Change in 6-minute Walk Distance (6MWD)

    Change from 6MWD at baseline (during screening visit) to 6MWD following RT234 dosing

    Measured: Baseline 6MWD at baseline (during screening visit) and 6MWD measured ~ 30 minutes following RT234 dosing at visit 4, which typically occurred 4-6 weeks following the screening visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2020
  2. Study start25 Sep 2020
  3. Primary completion20 Nov 2024
  4. Study completion7 Jan 2025

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04266197
Sponsor's protocol ID
RT234-PAH-CL202
Acronym
VIPAH-PRN_2B
Status last verified
Jun 2026
First submitted
22 Jan 2020
Last updated
13 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Benza RL, Franco V, Aras MA, Spikes L, Grinnan D, Satler C. Safety and efficacy of RT234 vardenafil inhalation powder on exercise parameters in pulmonary arterial hypertension: phase II, dose-escalation study design. Respir Res. 2022 Dec 17;23(1):355. doi: 10.1186/s12931-022-02262-9.

    PubMed 36527025

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI) in people with Pulmonary Arterial Hypertension, run by Respira Therapeutics, Inc. at 26 sites in United States.

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 39 inclusion and 35 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 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. 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?

Yes. Results are posted in the registry (first posted 17 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Mean Change in Peak Oxygen Uptake at Peak Exercise During CPET (Peak VO2) (time frame: Comparison of measure between baseline and treatment CPETs, typically ~14 days apart). The study lists 2 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 NCT04266197, which also lists 1 linked publication.

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 13 Jul 2026.

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