A Healthy Volunteer Study Evaluating the the Safety, Tolerability, and Pharmacokinetics of RT234

Respira Therapeutics

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteer

Treatments: Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI); Drug: Vardenafil Oral Tablet

Study type: Interventional

Funder types: Industry

Identifiers

NCT05567367

ACTRN12618001077257 (Registry Identifier)

RT234-CL101

Details and patient eligibility

About

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

Full 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.

Enrollment: 31 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 6 patient groups

RT234 0.2 mg, Single Ascending Dose (SAD)

Experimental group

Description:

Part 1, SAD Cohort 1A

Treatment:

Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)

RT234 0.6 mg followed by oral vardenafil 20mg on day 3, SAD

Experimental group

Description:

Part 1, SAD Cohort 2A1

Treatment:

Drug: Vardenafil Oral Tablet

Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)

Oral vardenafil 20mg followed by RT234 0.6 mg on day 3, SAD

Experimental group

Description:

Part 1, SAD Cohort 2A2

Treatment:

Drug: Vardenafil Oral Tablet

Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)

RT234 1.2 mg, SAD

Experimental group

Description:

Part 1, SAD Cohort 3A

Treatment:

Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)

RT234 2.4 mg, SAD

Experimental group

Description:

Part 1, SAD Cohort 4A

Treatment:

Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)

RT234 2.4 mg, Multiple Ascending Dose (MAD)

Experimental group

Description:

Part 2, MAD Cohort 1B

Treatment:

Combination Product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI)