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

Phase 1

Completed

• Conditions: Healthy Volunteer
• Interventions: Drug: Vardenafil Oral Tablet

• Registration Number: NCT05567367
• Lead Sponsor: Respira Therapeutics, Inc.

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.

Study Timeline

• Study Start: 2018-07-31
• Primary Completion: 2019-12-04
• Study Completion: 2019-12-04
• Study First Submitted: 2022-04-04
• Status Verified: 2022-10
• Study First Submitted QC: 2022-10-02
• Study First Posted: 2022-10-05
• Last Update Submitted: 2022-11-02
• Last Update Posted: 2022-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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)

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RT234 0.6 mg followed by oral vardenafil 20mg on day 3, SAD	Vardenafil Oral Tablet	Part 1, SAD Cohort 2A1
Oral vardenafil 20mg followed by RT234 0.6 mg on day 3, SAD	Vardenafil Oral Tablet	Part 1, SAD Cohort 2A2

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Total volume of distribution at the terminal phase	Up to 10 days	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
Time to reach maximum concentration (Tmax)	Up to 10 days	Tmax was measured for 4 single doses of oral vardenafil.
Peak plasma concentration (Cmax)	Up to 10 days	Cmax 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
Terminal elimination rate constant (Kel)	Up to 10 days	Kel was measured for 4 single doses of RT234
Total body clearance (CL/F)	Up to 10 days	CL/F was measured for 4 single doses of RT234

Trial Locations

Locations (1)

Nucleus Network, Burnet Institute; 🇦🇺 Prahran, Victoria, Australia