Healthy Volunteer
Conditions
Keywords
Pulmonary Arterial Hypertension, Familial Primary Pulmonary Hypertension, Vascular Diseases, Cardiovascular Diseases, Hypertension, Pulmonary, Lung Diseases, Respiratory Tract Diseases, Vardenafil Dihydrochloride, Inhaled Vardenafil, Vasodilator Agents, Phosphodiesterase 5 Inhibitors, Phosphodiesterase Inhibitors, Enzyme Inhibitors, Molecular Mechanisms of Pharmacological Action
Brief summary
The objective of this two part study was to demonstrate safety, tolerability, and pharmacokinetics of RT234 in healthy volunteers. This study is also known as Vardenafil Inhaled for Pulmonary Arterial Hypertension PRN Phase 1 (VIPAH-PRN 1) study
Detailed description
This study was designed to evaluate safety and tolerability and to characterize the PK profiles of single and repeated doses of inhaled vardenafil as RT234. In addition, vardenafil PK after single 0.6 mg doses of RT234 was compared to that following administration of a single 20 mg dose of oral vardenafil tablets.
Interventions
COMBINATION_PRODUCTDrug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)
RT234 is a drug/device combination product composed of vardenafil hydrochloride as the drug constituent and will utilize RS01 DPI device.
DRUGVardenafil Oral Tablet
20 mg oral vardenafil tablet.
Sponsors
Respira Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male or female, 18 to 45 years of age (inclusive at time of informed consent) 2. Normal heart, lung, kidney, and liver function based on physical examination 3. Systolic blood pressure of 100-145 mmHg, diastolic blood pressure of 50-90 mmHg, and a resting heart rate of 40-100 bpm at Screening 4. A body mass index (BMI) of ≤18 to ≥30 kg/m2 at Screening 5. Must be a non-smoker or ex-smoker with less than a 5-pack year history of smoking (including the use of electronic cigarettes) and have ceased smoking ≥1 year prior to Screening; or a social smoker (defined as less than 10 cigarettes in the previous 12 months)
Exclusion criteria
1. Has serum transaminase (i.e., alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], or gamma-glutamyl transferase \[GGT\]) levels greater than three times the upper level of normal 2. Abnormal orthostatic vital signs (at screening) defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure and/or \>25 bpm increase in heart rate within 3 minutes of standing, or with symptoms of light-headedness, dizziness, or fainting upon standing. 3. History of hypotension including fainting, syncope, orthostatic hypotension, and/or vasovagal reactions 4. History of retinitis pigmentosa 5. Vision loss due to non-arteritic anterior ischemic optic neuropathy (NAION) or other optic perfusion impairment 6. History of priapism or anatomical deformation of the penis 7. History of sudden sensorineural hearing loss (SSHL), need for hearing aids, and/or other documented hearing loss 8. A corrected QT interval using Fridericia's formula (QTcF) \>450 msec 9. Has evidence of significant obstructive lung disease on spirometry. Subjects with any of the following criteria will be excluded: 1. FEV1 \<60% (predicted) (pre-bronchodilators); or 2. FEV1/FVC \<65% (pre-bronchodilators)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment related adverse events as assessed by CTCAE v5.0 | Up to to 10 days | Adverse events reported by participants and those observed by the investigator in relation to laboratory tests, vital signs, ECGs, medications used to treat adverse events, and physical examinations were analyzed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to reach maximum concentration (Tmax) | Up to 10 days | Tmax was measured for 4 single doses of oral vardenafil. |
| Area under the curve (AUC) | Up to 10 days | AUC was measured for 4 single doses of RT234 |
| Half life (t1/2) | Up to 10 days | t1/2 was measured for 4 single doses of RT234 |
| Peak plasma concentration (Cmax) | Up to 10 days | Cmax was measured for 4 single doses of oral vardenafil. |
| Total body clearance (CL/F) | Up to 10 days | CL/F was measured for 4 single doses of RT234 |
| Total volume of distribution at the terminal phase | Up to 10 days | measured for 4 single doses of RT234 |
| Terminal elimination rate constant (Kel) | Up to 10 days | Kel was measured for 4 single doses of RT234 |
Countries
Australia
Outcome results
None listed