Summary

Eligibility
for people ages 18-80 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Mandar Aras
Photo of Mandar Aras
Mandar Aras

Description

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).

Official Title

A Phase 2, 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)

Details

Consequences of pulmonary arterial hypertension are significant limitations in cardiorespiratory fitness (CRF), exercise capacity, as well as profound dyspnea with physical exertion. The objective of the present 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.

Keywords

Pulmonary Arterial Hypertension Cardiopulmonary Exercise Test Familial Primary Pulmonary Hypertension Hypertension Vardenafil Dihydrochloride Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI) RT234-vardenafil inhalation powder

Eligibility

You can join if…

Open to people ages 18-80

  1. Must be between 18 and 80 years of age, inclusive.
  2. Must be willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
  3. Must be willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures.
  4. Diagnosis of Right Heart Catheterization (RHC) confirmed World Health

Organization (WHO) Group 1 PAH in any of the following three 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 (CTD):
  3. 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:
  4. 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 one-year post- surgical repair; iii. 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, are excluded.
  5. Previous diagnosis with PAH, but with the following conditions:
  6. Stable PAH without significant adjustments of disease-specific background PAH therapy, at least 3 months prior to CPET procedure;
  7. 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 CPET.
  8. Pulmonary Function Test (PFT) within 36 months prior to CPET procedure that fulfill the following criteria:
  9. Forced Expiratory volume in one second (FEV1) ≥ 60% predicted (pre-bronchodilators);
  10. FEV1/forced expiratory vital capacity (FVC) ≥ 60% (pre-bronchodilators);
  11. FVC ≥ 60% predicted.
  12. Has had RHC performed within 36 months of Screening/Baseline that is consistent with the diagnosis of PAH meeting all of the following criteria:
  13. Mean pulmonary artery pressure (mPAP) ≥ 20 mmHg (at rest); and
  14. Pulmonary artery wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 300 to < 500 dyne/sec/cm5, or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dynes/sec/cm5

If PCWP is not available, then mean left atrial pressure (mLAP) or left ventricular- end diastolic pressure (LVEDP) ≤ 15 mmHg or ≤ 12 mmHg in the absence of left atrial obstruction; and

  1. Pulmonary vascular resistance (PVR) > 3 Wood units or > 240 dyn.sec/cm5.
  2. Has WHO/NYHA functional class II-IV symptomatology.
  3. On stable oral PAH disease-specific therapy with any combination of an endothelin receptor antagonist (ERA), PDE- 5 inhibitor (PDE5i) and/or a prostacyclin or prostacyclin receptor agonist. Stable is defined as no change in drug within 3 months of the start of Screening/Baseline and for the duration of the study and no change in dose of drug within 1 month of the start of Screening.
  4. . Has a 6-minute walk distance (6MWD) of ≥ 50 meters and < 550 meters.
  5. . Has a VE/VCO2 slope ≥ 36 during the Screening/Baseline CPET (as assessed by the study Core Laboratory).
  6. . If the subject is taking the following concomitant medications which may affect PAH, the subject must be on a stable dose for at least 1 month prior to the start of Screening/Baseline and the dosage maintained throughout the study.
  7. Vasodilators (including calcium channel blockers -specify the indication e.g., PAH, HTN, Raynaud's), digoxin, or L-Arginine supplementation;
  8. If the subject is taking anticoagulants, then anticoagulation status should be maintained/stable in the therapeutic range for at least 1 month before the start of Screening/Baseline.
  9. . Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
  10. . Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests while participating in the study.
  11. . Females considered not of childbearing potential include those to be 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.

You CAN'T join if...

  1. Baseline systemic hypotension defined as mean arterial pressure (MAP) < 50 mmHg or systolic blood pressure (SBP) < 90 mmHg at Screening/Baseline.
  2. Requirement of intravenous inotropes within 30 days prior to CPET procedure.
  3. The use of oral, topical, or inhaled nitrates within 2 weeks prior to CPET procedure.
  4. Has uncontrolled systemic hypertension as evidenced by sitting SBP > 160 mmHg or sitting diastolic blood pressure > 100 mmHg at Screening/Baseline.
  5. Portal hypertension or chronic liver disease i.e., Child-Pugh B or C, including hepatitis B 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. Baseline aspartate aminotransferase (AST) or alanine transaminase (ALT) ≥ 3 times the upper limit of normal or Total Bilirubin ≥ 2 times the upper limit of normal.
  6. Evidence or history of left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
  7. Echocardiogram (ECHO) within 36 months prior to Screening demonstrating significant left sided heart disease including LV ejection fraction < 40%;
  8. Left Atrial Volume index (LAVi) > 30 mL/m2;
  9. Severe known symptomatology of coronary artery disease, or suspected history of coronary artery disease;
  10. Mitral or aortic valvular disease (stenosis or regurgitation) if moderate or severe;
  11. Restrictive, Dilated or Obstructive Cardiomyopathy;
  12. Percutaneous coronary intervention within the 6 months before Screening.
  13. History of atrial septostomy.
  14. History of known uncorrected right-to-left shunt, persistently patent foramen ovale, or known Eisenmenger's physiology.
  15. Paroxysmal or uncontrolled atrial fibrillation.
  16. . Diagnosis of Down Syndrome.
  17. . 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.
  18. . Hemoglobin (Hgb) concentration < 9 g/dL at screening.
  19. . For subjects with HIV associated PAH, any of the following:
  20. Concomitant active opportunistic infections within 6 months prior to Screening;
  21. Detectable viral load within 3 months of Screening;
  22. Cluster designation 4 (CD4+) T-cell count < 200 mm3 within 3 months of Screening;
  23. Changes in antiretroviral regimen within 3 months of Screening.
  24. . Malignancy within 5 years of the Screening Visit with the exception of localized non-metastatic basal cell carcinoma of the skin and in-situ carcinoma of the cervix excised with curative intent.
  25. . Recent history (within 2 years prior to the Screening Visit) of alcohol or drug/solvent abuse.
  26. . Known hypersensitivity to active drug substance (vardenafil) or drugs of the same class, or any excipients of the drug formulation(s).
  27. . History of hypotension including fainting, syncope, orthostatic hypotension, and/or vasovagal reactions.
  28. . Vision loss due to non-arteritic anterior ischemic optic neuropathy (NAION) or other optic perfusion impairment.
  29. . History of sudden sensorineural hearing loss (SSHL).
  30. . 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/Baseline.(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).
  31. . Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time while participating in the study.
  32. . Participation in a drug, device, or other interventional clinical study, other than a post-marketing observational extension study within 30 days prior to Screening.
  33. . Participation in a pulmonary rehabilitation/structured exercise training program within 6 months prior to screening.
  34. . 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.
  35. . Investigators, study staff, or their immediate family.

Locations

  • University of California San Francisco not yet accepting patients
    San Francisco California 94143 United States
  • The University of Kansas Medical Center accepting new patients
    Kansas City Kansas 66160 United States

Lead Scientist at UCSF

  • Mandar Aras
    My clinical interests are in the evaluation and management of patients with advanced heart failure and pulmonary hypertension, including patients requiring heart transplantation and left ventricular assist devices. I have a particular interest in prevention and treatment of patients with heart disease related to chemotherapy.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Respira Therapeutics, Inc.
ID
NCT04266197
Phase
Phase 2
Study Type
Interventional
Last Updated