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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Combination product: Drug: RT234 - vardenafil inhalation powder; Device: RS01 dry powder inhaler (RS01 DPI); Drug: Vardenafil Oral Tablet

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 Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Prahran, Victoria, Australia, 3004
      • Nucleus Network, Burnet Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RT234 0.2 mg, Single Ascending Dose (SAD); Part 1, SAD Cohort 1A	Combination product: Drug: 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.; Other Names: vardenafil inhalation powder
Experimental: RT234 0.6 mg followed by oral vardenafil 20mg on day 3, SAD; Part 1, SAD Cohort 2A1	Combination product: Drug: 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.; Other Names: vardenafil inhalation powder; Drug: Vardenafil Oral Tablet; 20 mg oral vardenafil tablet.; Other Names: Levitra
Experimental: Oral vardenafil 20mg followed by RT234 0.6 mg on day 3, SAD; Part 1, SAD Cohort 2A2	Combination product: Drug: 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.; Other Names: vardenafil inhalation powder; Drug: Vardenafil Oral Tablet; 20 mg oral vardenafil tablet.; Other Names: Levitra
Experimental: RT234 1.2 mg, SAD; Part 1, SAD Cohort 3A	Combination product: Drug: 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.; Other Names: vardenafil inhalation powder
Experimental: RT234 2.4 mg, SAD; Part 1, SAD Cohort 4A	Combination product: Drug: 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.; Other Names: vardenafil inhalation powder
Experimental: RT234 2.4 mg, Multiple Ascending Dose (MAD); Part 2, MAD Cohort 1B	Combination product: Drug: 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.; Other Names: vardenafil inhalation powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment related adverse events as assessed by CTCAE v5.0	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.	Up to to 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration (Cmax)	Cmax was measured for 4 single doses of oral vardenafil.	Up to 10 days
Time to reach maximum concentration (Tmax)	Tmax was measured for 4 single doses of oral vardenafil.	Up to 10 days
Area under the curve (AUC)	AUC was measured for 4 single doses of RT234	Up to 10 days
Half life (t1/2)	t1/2 was measured for 4 single doses of RT234	Up to 10 days
Terminal elimination rate constant (Kel)	Kel was measured for 4 single doses of RT234	Up to 10 days
Total body clearance (CL/F)	CL/F was measured for 4 single doses of RT234	Up to 10 days
Total volume of distribution at the terminal phase	measured for 4 single doses of RT234	Up to 10 days

Collaborators and Investigators

• Sponsor: Respira Therapeutics, Inc.
• Investigators: Study Director: Donna Jarlenski, MS, Respira Therapeutics

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2018
• Primary Completion (Actual): December 4, 2019
• Study Completion (Actual): December 4, 2019

Study Registration Dates

• First Submitted: April 4, 2022
• First Submitted That Met QC Criteria: October 2, 2022
• First Posted (Actual): October 5, 2022

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Pulmonary Arterial Hypertension; Enzyme Inhibitors; Vasodilator Agents; Molecular Mechanisms of Pharmacological Action; Hypertension, Pulmonary; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Familial Primary Pulmonary Hypertension; Vardenafil Dihydrochloride; Inhaled Vardenafil
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Vardenafil Dihydrochloride
• Other Study ID Numbers: RT234-CL101; ACTRN12618001077257 (Registry Identifier: Australian New Zealand Clinical Trials Registry (ANZCTR))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes