Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2B Study (VIPAH-PRN 2B)

February 9, 2023 updated by: Respira Therapeutics, Inc.

A Phase 2b, Open-label, Single Dose Study to Evaluated 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 effects of RT234 on exercise parameters assessed by a specialized exercise test (Cardiopulmonary Exercise Test or CPET) in patients with pulmonary arterial hypertension (PAH).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Consequences of PAH are 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 lower the sensation of dyspnea with physical exertion compared to baseline CPET measures.

Study Type

Interventional

Enrollment (Anticipated)

86

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
    • Arizona
      • Tucson, Arizona, United States, 85724
        • Recruiting
        • University of Arizona
    • California
      • Los Angeles, California, United States, 90024
      • Sacramento, California, United States, 95618
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Not yet recruiting
        • MedStar Heart and Vascular Institute
    • Georgia
      • Atlanta, Georgia, United States, 30342
      • Augusta, Georgia, United States, 30912
    • Illinois
      • Chicago, Illinois, United States, 60631
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • The University of Kansas Medical Center
        • Contact:
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Recruiting
        • Norton Health
    • Louisiana
      • Shreveport, Louisiana, United States, 71103
    • Massachusetts
    • Missouri
      • Saint Louis, Missouri, United States, 63110
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
    • Ohio
      • Cleveland, Ohio, United States, 44106
      • Columbus, Ohio, United States, 43210
    • Texas
      • Temple, Texas, United States, 76508
    • Virginia
      • Richmond, Virginia, United States, 23284
        • Recruiting
        • Virginia Commonwealth University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Ages 18 and 80 years, inclusive.

  2. Diagnosis of Right Heart Catheterization (RHC)-confirmed WHO Group 1 PAH in any of the following 3 categories:

    1. Idiopathic, primary, or familial pulmonary arterial hypertension (IPAH, PPH, or FPAH) OR
    2. 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
    3. 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 1-year post-surgical repair; iii. Exposure to legal drugs, chemicals and toxins, such as fenfluramine, derivatives, other anorexigens, toxic rapeseed oil, or L-tryptophan.
  3. The patient must have had a ventilation/perfusion (V/Q) scan, computerized tomography angiogram, or pulmonary arteriogram that rules out chronic thromboembolic pulmonary hypertension (CTEPH).

  4. Previous diagnosis with PAH, but with the following conditions:

    1. Stable PAH without significant adjustments of disease-specific background PAH therapy, at least 3 months prior to the 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 within 1 month of Screening.

      AND

    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 the baseline CPET.
  5. PFT within 6 months prior to the baseline CPET.
  6. Has had RHC performed prior to Screening which is consistent with the diagnosis of PAH.
  7. Has WHO/NYHA functional class II-IV symptomatology.
  8. On stable oral PAH disease-specific background therapy of up to 3 oral therapies (any combination of an ERA, PDE5 inhibitor, and/or a prostacyclin or prostacyclin receptor agonist) and/or inhaled therapy. 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 within 1 month of Screening.
  9. Must be able to walk a distance of at least 150 meters on the 6MWT. This will be determined using the mean of the two 6MWT results done between Visits 1 and 2.

  10. 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.

    1. Vasodilators
    2. Anticoagulants

Exclusion Criteria:

  1. Baseline systemic hypotension defined as MAP < 50 mmHg or SBP < 90 mmHg at Screening.
  2. History of chronic uncontrolled asthma.
  3. Requirement of intravenous inotropes therapies within 30 days prior to the baseline CPET procedure.
  4. Use of PAH medications that are not taken by mouth.
  5. Use of oral, topical, or inhaled nitrates within 2 weeks prior to the baseline CPET procedure.
  6. Has uncontrolled systemic hypertension
  7. 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 allowed.
  8. Evidence or history of left-sided heart disease and/or clinically significant cardiac disease.
  9. History of atrial septostomy.
  10. History of known uncorrected right-to-left shunt, clinically significant persistently patent foramen ovale, or known Eisenmenger's physiology.
  11. Paroxysmal or uncontrolled atrial fibrillation.
  12. Diagnosis of Down syndrome.
  13. 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.
  14. Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is ≥3 x the upper limit of the normal range.
  15. Platelets below 50,000/μL at Screening.
  16. Hemoglobin (Hgb) concentration < 9 g/dL at Screening.

  17. For subjects with HIV-associated PAH, any of the following:

    1. Concomitant active opportunistic infections within 6 months prior to Screening;
    2. Detectable viral load within 3 months of Screening;
    3. CD4+ T-cell count < 200/mm^3 within 3 months prior to Screening;
    4. Changes in antiretroviral regimen within 3 months prior to Screening.
  18. Malignancy within 5 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.
  19. History of hypotension including fainting, syncope, orthostatic hypotension, and/or vasovagal reactions.
  20. Vision loss due to non-arteritic anterior ischemic optic neuropathy or other optic perfusion impairment.
  21. History of sudden sensorineural hearing loss.
  22. Male subjects with a corrected QT interval using Fridericia's formula (QTcF) > 450 msec and female subjects with QTcF > 470 msec on electrocardiogram (ECG) measured at Screening.
  23. Participation in a drug, device, or other interventional clinical study, other than post-marketing observational extension study, within 30 days prior to Screening.
  24. Participation in the active phase (other than the maintenance phase) of a pulmonary rehabilitation/structured exercise training program within 6 months prior to Screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: RT234 0.5 mg Cohort 1
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 capsules of a dry powder formulation containing vardenafil administered via oral inhalation with a non-invasive AOS DPI.
Other Names:
  • inhaled vardenafil
EXPERIMENTAL: RT234 1.0 mg Cohort 2
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 capsules of a dry powder formulation containing vardenafil administered via oral inhalation with a non-invasive AOS DPI.
Other Names:
  • inhaled vardenafil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From baseline to follow-up day 15 post-treatment
TEAEs as grouped by MedDRA system organ class and relationship to treatment.
From baseline to follow-up day 15 post-treatment
Change in Vital Signs
Time Frame: From baseline to follow-up day 15 post-treatment
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 15 post-treatment
Change in peak oxygen consumption (VO2) assessed by CPET
Time Frame: From baseline to 15 minutes post-treatment
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in 6-minute walk distance (6MWD)
Time Frame: From baseline to 15 minutes post-treatment
Change from mean Screening in 6MWD when 6-minute walk test (6MWT) is performed 15 minutes post-RT234 dosing.
From baseline to 15 minutes post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Respira Therapeutics, Inc.

Investigators

  • Study Chair: Carol Ann Satler, MD, PhD, Respira Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 25, 2020

Primary Completion (ANTICIPATED)

December 1, 2023

Study Completion (ANTICIPATED)

April 1, 2024

Study Registration Dates

First Submitted

January 22, 2020

First Submitted That Met QC Criteria

February 10, 2020

First Posted (ACTUAL)

February 12, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 10, 2023

Last Update Submitted That Met QC Criteria

February 9, 2023

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RT234-PAH-CL202

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

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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