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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
Sponsored by
Respira Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Cardiopulmonary Exercise Test, 6MWT

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of AlabamaRecruiting
  • University of ArizonaRecruiting
  • UCLARecruiting
  • UC DavisRecruiting
  • University of California San FranciscoRecruiting
  • MedStar Heart and Vascular Institute
  • Accel Clinical Research/Atlanta Clinical Research CentersRecruiting
  • Augusta UniversityRecruiting
  • University of Chicago Medical CenterRecruiting
  • The University of Kansas Medical CenterRecruiting
  • Norton HealthRecruiting
  • Ochsner Louisiana State University HealthRecruiting
  • Tufts UniversityRecruiting
  • Washington UniversityRecruiting
  • University of New MexicoRecruiting
  • University HospitalRecruiting
  • The Ohio State UniversityRecruiting
  • Baylor Scott & White Medical CenterRecruiting
  • Virginia Commonwealth UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

RT234 0.5 mg Cohort 1

RT234 1.0 mg Cohort 2

Arm Description

RT234 at a capsule dose strength of 0.5 mg.

RT234 at a capsule dose strength of 1.0 mg.

Outcomes

Primary Outcome Measures

Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
TEAEs as grouped by MedDRA system organ class and relationship to 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).
Change in peak oxygen consumption (VO2) assessed by CPET
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.

Secondary Outcome Measures

Change in 6-minute walk distance (6MWD)
Change from mean Screening in 6MWD when 6-minute walk test (6MWT) is performed 15 minutes post-RT234 dosing.

Full Information

First Posted
January 22, 2020
Last Updated
February 9, 2023
Sponsor
Respira Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04266197
Brief Title
Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2B Study
Acronym
VIPAH-PRN 2B
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2020 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Respira Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Cardiopulmonary Exercise Test, 6MWT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
86 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RT234 0.5 mg Cohort 1
Arm Type
Experimental
Arm Description
RT234 at a capsule dose strength of 0.5 mg.
Arm Title
RT234 1.0 mg Cohort 2
Arm Type
Experimental
Arm Description
RT234 at a capsule dose strength of 1.0 mg.
Intervention Type
Combination Product
Intervention Name(s)
Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
Other Intervention Name(s)
inhaled vardenafil
Intervention Description
RT234 capsules of a dry powder formulation containing vardenafil administered via oral inhalation with a non-invasive AOS DPI.
Primary Outcome Measure Information:
Title
Incidence and severity of Treatment-Emergent Adverse Events (TEAEs)
Description
TEAEs as grouped by MedDRA system organ class and relationship to treatment.
Time Frame
From baseline to follow-up day 15 post-treatment
Title
Change in Vital Signs
Description
This variable will include mean arterial blood pressure expressed in mmHg (calculated utilizing recorded systolic and diastolic blood pressures in mmHg).
Time Frame
From baseline to follow-up day 15 post-treatment
Title
Change in peak oxygen consumption (VO2) assessed by CPET
Description
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.
Time Frame
From baseline to 15 minutes post-treatment
Secondary Outcome Measure Information:
Title
Change in 6-minute walk distance (6MWD)
Description
Change from mean Screening in 6MWD when 6-minute walk test (6MWT) is performed 15 minutes post-RT234 dosing.
Time Frame
From baseline to 15 minutes post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ages 18 and 80 years, inclusive. Diagnosis of 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 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. 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). Previous diagnosis with PAH, but with the following conditions: 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 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 the baseline CPET. Has had RHC performed prior to Screening which is consistent with the diagnosis of PAH. Has WHO/NYHA functional class II-IV symptomatology. 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. 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. 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 Anticoagulants Exclusion Criteria: Baseline systemic hypotension defined as MAP < 50 mmHg or SBP < 90 mmHg at Screening. History of chronic uncontrolled asthma. Requirement of intravenous inotropes therapies within 30 days prior to the baseline CPET procedure. Use of PAH medications that are not taken by mouth. Use of oral, topical, or inhaled nitrates within 2 weeks prior to the baseline CPET procedure. Has uncontrolled systemic hypertension 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. Evidence or history of left-sided heart disease and/or clinically significant cardiac disease. History of atrial septostomy. History of known uncorrected right-to-left shunt, clinically significant persistently patent foramen ovale, or known Eisenmenger's physiology. Paroxysmal or uncontrolled atrial fibrillation. Diagnosis of Down syndrome. 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 ≥3 x the upper limit of the normal range. Platelets below 50,000/μL at Screening. Hemoglobin (Hgb) concentration < 9 g/dL at Screening. For subjects with HIV-associated PAH, any of the following: Concomitant active opportunistic infections within 6 months prior to Screening; Detectable viral load within 3 months of Screening; CD4+ T-cell count < 200/mm^3 within 3 months prior to Screening; Changes in antiretroviral regimen within 3 months prior to Screening. 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. 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 electrocardiogram (ECG) measured at Screening. Participation in a drug, device, or other interventional clinical study, other than post-marketing observational extension study, within 30 days prior to Screening. Participation in the active phase (other than the maintenance phase) of a pulmonary rehabilitation/structured exercise training program within 6 months prior to Screening.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Study Director
Phone
646-224-4901
Email
csatler@respiratherapeutics.com
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Individual Site Status
Recruiting
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Individual Site Status
Recruiting
Facility Name
UC Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95618
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Name
MedStar Heart and Vascular Institute
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Accel Clinical Research/Atlanta Clinical Research Centers
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Recruiting
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60631
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Individual Site Status
Recruiting
Facility Name
Norton Health
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Individual Site Status
Recruiting
Facility Name
Ochsner Louisiana State University Health
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71103
Country
United States
Individual Site Status
Recruiting
Facility Name
Tufts University
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Individual Site Status
Recruiting
Facility Name
University Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
Baylor Scott & White Medical Center
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Individual Site Status
Recruiting
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23284
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2B Study

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