Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2B Study

NCT04266197 | Completed Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: RT234-PAH-CL202
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 26

Brief 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).

Conditions

Pulmonary Arterial Hypertension

Keywords

Cardiopulmonary Exercise Test; 6MWT

Outcome Measures

Primary Outcomes (3)

• Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)

  TEAEs as grouped by MedDRA system organ class and relationship to treatment.

  From baseline to follow-up day 30 post-treatment

• Change in Vital Signs

  This variable will include mean arterial blood pressure expressed in mmHg (calculated utilizing recorded systolic and diastolic blood pressures in mmHg).

  From baseline to follow-up day 30 post-treatment

• Change in peak oxygen consumption (VO2) assessed by CPET after RT234 dosing

  This variable will be assessed by ventilatory expired gas analysis during exercise testing and will be expressed in ml/ kg/min. Mean values from baseline to post-treatment will be compared.

  From baseline to 15 minutes post-treatment

Secondary Outcomes (2)

• Change in 6-minute walk distance (6MWD)

  From baseline to 15 minutes post-treatment

• Change in perceived dyspnea

  From baseline to 15 minutes post-treatment

Study Arms (3)

RT234 0.5 mg Cohort 1

EXPERIMENTAL

RT234 at a capsule dose strength of 0.5 mg.

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

RT234 1.0 mg Cohort 2

EXPERIMENTAL

RT234 at a capsule dose strength of 1.0 mg.

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

RT234 2.0 mg Cohort 3

EXPERIMENTAL

RT234 at a capsule dose strength of 2.0 mg.

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

Interventions

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

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

Also known as: inhaled vardenafil

RT234 0.5 mg Cohort 1; RT234 1.0 mg Cohort 2; RT234 2.0 mg Cohort 3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• PAH associated with one of the following connective tissue diseases:
• i) 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.
• iii) 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:

You may not qualify if:

• 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.
• 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:
• i) 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.
• iv) Positive stress test imaging, either pharmacologic or with exercise. v) Previous coronary artery surgery. vi) Chronic stable angina.

Sponsors & Collaborators

• Respira Therapeutics, Inc.: lead

Study Sites (26)

University of Alabama

Birmingham, Alabama, 35294, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

UCLA

Los Angeles, California, 90024, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

UC Davis

Sacramento, California, 95618, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

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

Torrance, California, 90502, United States

Location

MedStar Heart and Vascular Institute

Washington D.C., District of Columbia, 20010, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Norton Health

Louisville, Kentucky, 40202, United States

Location

Ochsner Louisiana State University Health

Shreveport, Louisiana, 71103, United States

Location

Tufts University

Boston, Massachusetts, 02111, United States

Location

Mayo Clinic

Rochester, Minnesota, 20010, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

University Hospital

Cleveland, Ohio, 44106, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Ascension Seton Medical Center Austin

Austin, Texas, 78705, United States

Location

Baylor Scott and White Institute

Dallas, Texas, 75246, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23284, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Related Publications (1)

• 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.

  PMID: 36527025 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ed Parsley, DO

  Respira Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: February 12, 2020
• Study Start: September 25, 2020
• Primary Completion: November 20, 2024
• Study Completion: January 7, 2025
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (26)