Open Actively Recruiting
Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 2B Study
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).
- 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.
- 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.
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