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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05567367
• Other study ID #: RT234-CL101
• Secondary ID: ACTRN12618001077
• Status: Completed
• Phase: Phase 1
• Start date: July 31, 2018
• Est. completion date: December 4, 2019

Study information

• Verified date: October 2022
• Source: Respira Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 4, 2019
• Est. primary completion date: December 4, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

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.

Drug:
• Vardenafil Oral Tablet
20 mg oral vardenafil tablet.

Locations

Country	Name	City	State
Australia	Nucleus Network, Burnet Institute	Prahran	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Respira Therapeutics, Inc.

Country where clinical trial is conducted

Australia, 

References & Publications (1)

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 De — View Citation

Outcome

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