Clinical trial NCT05567367: A Healthy Volunteer Study Evaluating the the Safety, Tolerability, and Pharmacokinetics of RT234
Official title: A Phase 1, Two-Part, Single-Center, Open-Label, Randomized, Cross-Over, Single Ascending Doses (SAD), Followed by a Multiple Ascending Doses (MAD) Safety and Pharmacokinetic Study of RT234 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
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
Lead sponsor: Respira Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-05
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of participants with treatment related adverse events as assessed by CTCAE v5.0
timeFrame: Up to to 10 days
Secondary outcomes:
measure: Peak plasma concentration (Cmax)
timeFrame: Up to 10 days
measure: Time to reach maximum concentration (Tmax)
timeFrame: Up to 10 days
measure: Area under the curve (AUC)
timeFrame: Up to 10 days
measure: Half life (t1/2)
timeFrame: Up to 10 days
measure: Terminal elimination rate constant (Kel)
timeFrame: Up to 10 days
measure: Total body clearance (CL/F)
timeFrame: Up to 10 days
measure: Total volume of distribution at the terminal phase
timeFrame: Up to 10 days
Other outcomes:
Locations:
city: Prahran
country: Australia
facility: Nucleus Network, Burnet Institute
state: Victoria
Study officials:
affiliation: Respira Therapeutics
name: Donna Jarlenski, MS
role: STUDY_DIRECTOR
References:
citation: Eldon MA, Parsley EL, Maurer M, Tarara TE, Okikawa J, Weers JG. Safety, Tolerability, and Pharmacokinetics of RT234 (Vardenafil Inhalation Powder): A First-in-Human, Ascending Single- and Multiple-Dose Study in Healthy Subjects. J Aerosol Med Pulm Drug Deliv. 2021 Aug;34(4):251-261. doi: 10.1089/jamp.2020.1651. Epub 2020 Dec 15.