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Trial record 4 of 9 for:    Vardenafil hypertension

Effects of RT234 on Exercise Parameters Accessed by CPET in Subjects With PAH

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ClinicalTrials.gov Identifier: NCT04266197
Recruitment Status : Recruiting
First Posted : February 12, 2020
Last Update Posted : June 24, 2021
Sponsor:
Collaborators:
Precision For Medicine
Argint International
Information provided by (Responsible Party):
Respira Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE January 22, 2020
First Posted Date  ICMJE February 12, 2020
Last Update Posted Date June 24, 2021
Actual Study Start Date  ICMJE September 25, 2020
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From screening to follow-up day 5 post-treatment CPET ]
    TEAEs as grouped by MedDRA system organ class and relationship to treatment.
  • Change in Blood Pressure [ Time Frame: From screening to follow-up day 5 post-treatment CPET ]
    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 [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline 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.
  • Change in Patient Global Impression of Severity (PGI-S) from baseline to post dose. [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    The PGI-S score is a self-rating scale to evaluate Shortness of Breath, Physical Fatigue, and Overall Symptom Severity.
  • Change in minute ventilation to carbon dioxide production (VE/VCO2) slope [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed by ventilatory expired gas analysis during exercise testing and will be expressed as a slope value. Mean values from baseline to post-treatment will be compared.
  • Change in PETCO2 apex response to exercise from baseline to post dose [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed by ventilatory expired gas analysis during exercise testing and will be expressed in mmHg. Mean values from baseline to post-treatment will be compared.
  • Change in duration of exercise during CPET from baseline to post dose [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed during exercise testing and will be expressed in seconds. Mean values from baseline to post-treatment will be compared.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • The proportion of subjects with improvement in risk category (i.e., low, intermediate, high) for VE/VCO2 slope criteria. [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    As defined in the European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines for the diagnosis and treatment of pulmonary hypertension.
  • Change in Modified Borg Dyspnea Score [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    The Modified Borg dyspnea score is a self-rating scale to evaluate the severity of dyspnea (from 0 "no breathlessness at all" to 10 "very, very severe / maximal"). It will be assessed every minute during exercise testing and 6-minutes in to recovery. Mean values from baseline to post-treatment will be compared.
  • Change in Borg Rating of Perceived Exertion (RPE) Score [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    The Borg RPE score is a self-rating scale to evaluate the severity of fatigue (from 6 "no exertion at all" to 20 "maximal exertion"). It will be assessed every 2-minutes during exercise testing and 6-minutes in to recovery. Mean values from baseline to post-treatment will be compared.
  • Change in oxygen consumption (VO2) at ventilatory threshold (VT) assessed by CPET [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline 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.
  • Change in Oxygen Uptake Efficiency Slope (OUES) [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed by ventilatory expired gas analysis during exercise testing and will be expressed as a slope value. Mean values from baseline to post-treatment will be compared.
  • Change in Respiratory Exchange Ratio (RER) [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed by ventilatory expired gas analysis during exercise testing and will be expressed as a ratio. Mean values from baseline to post-treatment will be compared.
  • Change in Systolic Blood Pressure (SBP) response to exercise from baseline to post dose [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed during exercise testing and will be expressed in mmHg. It will be assessed every 2-minutes during exercise testing and 6-minutes in to recovery. Mean values from baseline to post-treatment will be compared.
  • Change in pulse oximetry response to exercise from baseline to post dose [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed during exercise testing and will be expressed as a percentage (%). It will be assessed every minute during exercise testing and 6-minutes in to recovery. Mean values from baseline to post-treatment will be compared.
  • Change in atrial arrhythmia frequency during exercise from baseline to post dose [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed by electrocardiogram (ECG) during exercise testing. It will be assessed continuously during exercise testing and 6-minutes in to recovery. Frequency of atrial arrhythmias from baseline to post-treatment will be compared.
  • Change in ventricular arrhythmia frequency during exercise from baseline to post dose [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
    This variable will be assessed by electrocardiogram (ECG) during exercise testing. It will be assessed continuously during exercise testing and 6-minutes in to recovery. Frequency of ventricular arrhythmias from baseline to post-treatment will be compared.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 10, 2020)
Change in Duke Activity Status Index (DASI) [ Time Frame: Baseline CPET to post-treatment CPET at 7 to 14 days following Baseline CPET ]
The DASI is a a self-rating questionnaire that allows for an estimation of a subject's perceived exercise capacity.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effects of RT234 on Exercise Parameters Accessed by CPET in Subjects With PAH
Official Title  ICMJE 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)
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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
RT234 is a drug/device combination product composed of vardenafil hydrochloride as the drug constituent and will utilize AOS DPI device (RPC Plastiape, Osnago, Italy).
Other Name: inhaled vardenafil
Study Arms  ICMJE Experimental: RT234-vardenafil inhalation powder
RT234 at capsule dose strength of 0.5 mg. RT234 will be administered using a variant of the RS01 Monodose Dry Powder Inhaler named Axially Oscillating Sphere dry powder inhaler (AOS DPI) device (RPC Plastiape, Osnago, Italy).
Intervention: Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: Axially Oscillating Sphere dry powder inhaler (AOS DPI)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 21, 2021)
40
Original Estimated Enrollment  ICMJE
 (submitted: February 10, 2020)
20
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  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):

    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 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:

    1. Stable PAH without significant adjustments of disease-specific background PAH therapy, at least 3 months prior to CPET procedure;
    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 CPET.
  6. Pulmonary Function Test (PFT) within 36 months prior to CPET procedure that fulfill the following criteria:

    1. Forced Expiratory volume in one second (FEV1) ≥ 60% predicted (pre- bronchodilators);
    2. FEV1/forced expiratory vital capacity (FVC) ≥ 60% (pre-bronchodilators);
    3. FVC ≥ 60% predicted.
  7. Has had RHC performed within 36 months of Screening/Baseline that is consistent with the diagnosis of PAH meeting all of the following criteria:

    1. Mean pulmonary artery pressure (mPAP) ≥ 20 mmHg (at rest); and
    2. 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

    3. Pulmonary vascular resistance (PVR) > 3 Wood units or > 240 dyn.sec/cm5.
  8. Has WHO/NYHA functional class II-IV symptomatology.
  9. 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.
  10. Has a 6-minute walk distance (6MWD) of ≥ 50 meters and < 550 meters.
  11. Has a VE/VCO2 slope ≥ 36 during the Screening/Baseline CPET (as assessed by the study Core Laboratory).
  12. 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.

    1. Vasodilators (including calcium channel blockers -specify the indication e.g., PAH, HTN, Raynaud's), digoxin, or L-Arginine supplementation;
    2. 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.
  13. Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
  14. 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.
  15. 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.

Exclusion Criteria:

  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:

    1. Echocardiogram (ECHO) within 36 months prior to Screening demonstrating significant left sided heart disease including LV ejection fraction < 40%;
    2. Left Atrial Volume index (LAVi) > 30 mL/m2;
    3. Severe known symptomatology of coronary artery disease, or suspected history of coronary artery disease;
    4. Mitral or aortic valvular disease (stenosis or regurgitation) if moderate or severe;
    5. Restrictive, Dilated or Obstructive Cardiomyopathy;
    6. Percutaneous coronary intervention within the 6 months before Screening.
  7. History of atrial septostomy.
  8. History of known uncorrected right-to-left shunt, persistently patent foramen ovale, or known Eisenmenger's physiology.
  9. Paroxysmal or uncontrolled atrial fibrillation.
  10. Diagnosis of Down Syndrome.
  11. 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.
  12. Hemoglobin (Hgb) concentration < 9 g/dL at screening.
  13. 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. Cluster designation 4 (CD4+) T-cell count < 200 mm3 within 3 months of Screening;
    4. Changes in antiretroviral regimen within 3 months of Screening.
  14. 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.
  15. Recent history (within 2 years prior to the Screening Visit) of alcohol or drug/solvent abuse.
  16. Known hypersensitivity to active drug substance (vardenafil) or drugs of the same class, or any excipients of the drug formulation(s).
  17. History of hypotension including fainting, syncope, orthostatic hypotension, and/or vasovagal reactions.
  18. Vision loss due to non-arteritic anterior ischemic optic neuropathy (NAION) or other optic perfusion impairment.
  19. History of sudden sensorineural hearing loss (SSHL).
  20. 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).
  21. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time while participating in the study.
  22. Participation in a drug, device, or other interventional clinical study, other than a post-marketing observational extension study within 30 days prior to Screening.
  23. Participation in a pulmonary rehabilitation/structured exercise training program within 6 months prior to screening.
  24. 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.
  25. Investigators, study staff, or their immediate family.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kevin Corkery 6507433163 kcorkery@respiratherapeutics.com
Listed Location Countries  ICMJE Serbia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04266197
Other Study ID Numbers  ICMJE RT234-PAH-CL202
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Respira Therapeutics, Inc.
Study Sponsor  ICMJE Respira Therapeutics, Inc.
Collaborators  ICMJE
  • Precision For Medicine
  • Argint International
Investigators  ICMJE
Study Director: Shai Erlich, PhD Respira Therapeutics, Inc.
PRS Account Respira Therapeutics, Inc.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP