Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000563460
Ethics application status
Approved
Date submitted
10/04/2025
Date registered
2/06/2025
Date last updated
2/06/2025
Date data sharing statement initially provided
2/06/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to Evaluate the parameters of TRX-248 Transdermal System in Healthy Female Volunteers
Scientific title
A Phase 1 Study to Evaluate the Pharmacokinetics of Multiple Formulations of Once Daily TRX-248 Transdermal System in Healthy Female Volunteers
Secondary ID [1] 314062 0
PRO-CLNP1-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Arterial Hypertension 336809 0
Condition category
Condition code
Cardiovascular 333301 333301 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase 1, open-label, placebo-controlled, crossover study evaluating the pharmacokinetics, safety, and tolerability of multiple formulations of the TRX-248 transdermal system (TS) in healthy female volunteers. TRX-248 is an inert prodrug that will penetrate the skin, be metabolized in the liver and converted to active drug, tresprostinil.

Part A: Each participant will receive a single dose of TRX-248 TS (one active system) along with two placebo systems in each treatment period. The dose administered will depend on:
- the excipient/formulation, and
- the amount of TRX-248 in each formulation: 42.6 mg (formulation A), 71.0 mg (formulation B), or 30.0 mg (formulation C) TRX-248 per patch and
- on the surface area in direct contact with the TS.
There will be three treatment periods, each lasting 24 hours, followed by a washout period of at least 6 days before the next treatment.

Part B: Participants from Part A (9 subjects) will receive three active TRX-248 TS patches of either:
One of the three formulations (A, B, or C) tested in Part A or an optimized formulation (Formulation D), developed within the parameters of Formulations A, B, or C. The treatment period will last 24 hours, followed by a 6-day follow-up period. Each TRX-248 TS and each matching placebo will be applied to intact skin on preferably the back. Locations may be re-used after at least 2 week rest period.
Patch application and removal will be done by research staff while participant is in confinement at site, under close medical observation.
A sentinel treatment sequence will ensure that a single formulation will be tested in 1 participant for at least 1 day before proceeding to the next formulation, such that all 3 formulations are tested in a single participant before proceeding to fill the 9-subject cohort.
Intervention code [1] 330641 0
Treatment: Drugs
Comparator / control treatment
In Part A two matching placebo systems (one with an overlay, one without an overlay) will be used in each treatment period. The placebo patches serve as the control to compare the skin tolerability and adhesion of TRX-248 Transdermal System. Each formulation has a matching placebo, with the same composition of DMSO, ethanol, hexylene glycol, water/citrate buffer, methyl laurate, and hydroxypropyl cellulose, but without TRX-248 prodrug.
No placebo patches will be used for Part B.
Control group
Placebo

Outcomes
Primary outcome [1] 340879 0
Pharmacokinetic parameters — including Cmax, Tmax, t½, AUC0–t, AUC0–last, AUC0–8, apparent clearance, and volume of distribution — will be assessed for both TRX-248 and its active metabolite, treprostinil, using blood samples collected in Part A of the study.
Timepoint [1] 340879 0
Blood samples for pharmacokinetic analysis will be collected at the following timepoints relative to transdermal system (TS) application: During the 24-hour wear period: pre-dose (0), 1, 2, 4, 6, 10, 14, 18, and 24 hours (immediately prior to patch removal) After patch removal: 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 96, and 120 hours post-removal Samples up to 48 hours after application (or 24 hours post-removal) will be collected within ±5 minutes of the scheduled time, and remaining samples within ±2 hours.
Primary outcome [2] 341208 0
Pharmacokinetic parameters — including Cmax, Tmax, t½, AUC0–t, AUC0–last, AUC0–8, apparent clearance, and volume of distribution — will be assessed for both TRX-248 and its active metabolite, treprostinil, using blood samples collected in Part B of the study
Timepoint [2] 341208 0
Blood samples for pharmacokinetic analysis will be collected at the following timepoints relative to transdermal system (TS) application: During the 24-hour wear period: pre-dose (0), 1, 2, 4, 6, 10, 14, 18, and 24 hours (immediately prior to patch removal) After patch removal: 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 96, and 120 hours post-removal Samples up to 48 hours after application (or 24 hours post-removal) will be collected within ±5 minutes of the scheduled time, and remaining samples within ±2 hours.
Secondary outcome [1] 445334 0
To assess the overall safety and tolerability of TRX-248 TS formulations and matching placebo in healthy female volunteers during Part A.
Timepoint [1] 445334 0
Study staff will observe the application sites, and subjects will be asked about discomfort at the application sites at: 4, 8, 12, 16 and 24 hours post-TS application. Note: Skin at the application site will not be visible while the TS is applied. Staff assessment using skin appearance and other observed effects scoring scales, plus subject reporting, will be done at 0.5, 2, 24, 48, 72, 96, 120, 144 and 168 hours post-TS removal. This will continue on a daily basis if the combined score is greater than 1, until resolution.
Secondary outcome [2] 445335 0
To assess the safety and tolerability when multiple TRX-248 systems are applied during Part B
Timepoint [2] 445335 0
Pre dose and then at hours 1, 2, 4, 6, 10, 14, 18, 24 Post removal: 0.5, 1, 2, 4, 6, 12, 24, 48, 72, 96, and 120 hours

Eligibility
Key inclusion criteria
1. Healthy female adults.
2. Caucasian with light/pale skin aged 18 to 55 years (inclusive) on the day of Screening.
3. Body weight is greated than or equal to 55 kg and less than or equal to 80 kg.
4. Body Mass Index (BMI) between 18.5 to 32 kg/m² (inclusive) as calculated using the site standard procedures.
5. Willing and able to understand and participate in all scheduled evaluations by providing a signed and dated written informed consent prior to the initiation of any study procedures.
6. Negative pregnancy test at the Screening and Baseline Visit and agrees to practice adequate birth control throughout the duration of the study and for 32 days post last administration of IP. Subjects confirmed at Screening to be not pregnant and postmenopausal (follicle stimulating hormone [FSH] > 40 mIU/mL) will not require pregnancy testing at each admission.
7. Negative urine drug screen for drugs of abuse (list as per site protocol) unless there is documentation that the subject has been prescribed the corresponding medication and the medication is otherwise acceptable for the study.
8. Negative serology test for human immunodeficiency virus (HIV), hepatitis, tuberculosis (TB), and syphilis.
9. Use of tylenol (paracetamol), zofran (ondansetron) and imodium (loperamide) is permitted when-required (PRN). Concomitant medication may be allowed with Investigator/Sponsor approval if on stable dose (at least 28 days prior to randomization on Day 1). Hormonal contraceptives are allowed.
Minimum age
18 Years
Maximum age
55 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Participation in another clinical study with an investigational product (IP) or device within 60 days or 5 half-lives prior to Screening (days from last dose).
2. Plasma donation within 14 days of Screening or any blood donation or blood loss > 500 mL within 30 days of Screening.
3. Has skin color or tone that may not allow reliable evaluation of irritation.
4. Unwilling to abstain from strenuous physical exercise and from alcohol consumption for 48 hours prior to scheduled PK blood draws at the clinic visits.
5. Has intolerance to venipuncture and/or inability to comply with the extensive blood sampling required for this study or does not have suitable veins in both arms.
6. Has cuts, scratches/abrasions, scars, breaks in the skin surface, tattoos at the application sites, skin with excessive hair, indications of sunburn, excessive skin tanning, stretch marks, moles and/or similar abnormalities at the intended application sites which would affect absorption of the IP.
7. Unwilling to refrain from using tanning salons, saunas, or sunbathe during the conduct of the study. Unwilling to also refrain from shaving of application site, waxing of application site, or using lotion hair remover on or near application site from 21 days before TS application and during the conduct of the study.
8. Smoke more than 2 cigarettes per day, or vaping equivalent.
9. History of or current clinically important disease or disorder, including neurologic, pulmonary, hepatic, renal, metabolic, psychiatric, cardiovascular, gastrointestinal, endocrinologic, immunologic, hematologic, active cancer, clinically important infection, or other abnormality that may interfere with the evaluation or administration of the IP, interpretation of subject safety or study results, or would make participation in the study an unacceptable risk including any significant acute or chronic medical condition. It is the responsibility of the Investigator to assess the clinical significance; however, consultation with the Sponsor/Medical Monitor may be warranted. These include but are not limited to:
. Myocardial infarction, hospitalization for unstable angina or arrhythmia, or unexplained syncope within 6 months of Screening.
. Transient Ischemic Attack (TIA) or stroke within 6 months of Screening.
. History of severe allergy/hypersensitivity reactions or ongoing allergy/hypersensitivity reactions, or history of hypersensitivity to treprostinil or other prostacyclin drugs.
. History of allergy with skin reaction is excluded even if not considered clinically significant.
. History of allergy or sensitivity or hypersensitivity to the ingredients in the TS including glues/adhesives, topical alcohol, medical grade adhesive tapes, sunscreens, cosmetics, lotions, fragrances, and/or latex.
. History of allergy, dermatitis or sensitivity or hypersensitivity to band aids, ECG dots, or other adhesive.
. Any medical or surgical procedure or trauma within 28 days of Day 1.
10. Clinically significant finding in physical examination, vital signs, ECG or clinical laboratory tests at Screening or Day -1 that could
affect the subject’s safety or ability to complete the study, as judged by the Investigator.
. Hemoglobin < 110 g/L.
. Blood pressure: Systolic value 140/90 mmHg.
. AST (aspartate transaminase) or ALT (alanine transaminase) levels > 1.5 upper limit of normal (ULN).
. Creatinine clearance of < lower limit of normal (LLN) as determined by the Cockcroft-Gault formula.
. Positive pregnancy test at Screening or between Screening and randomization (fertile females only).
. Heart rate is less than or equal to 40 bpm.
. Assessment may be repeated once for eligibility determination at Screening or Day -1.
11. Use of any topical medication in the areas intended for TS application within 14 days prior to the first TS application and throughout the study.
12. Use of any topical products with or without medicinal ingredient (including but not limited to perfumes, body lotions, sunscreens, spray or TS oils, creams and alcohol) on the sites intended for TS application within 48 hours prior to the first TS application and throughout the study. Topical application of products without significant systemic absorption are allowed in areas other than the ones intended for TS application. Sponsor to be consulted with any questions.
13. Non-metastatic basal cell carcinoma of the skin, completely resected squamous skin cancer with no recurrence for 12 months, carcinoma in situ of the cervix may be enrolled with prior approval from Corsair.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomised based on eligibility order to a treatment sequence. First three participants assigned to Latin Square A in random order (ABC, BCA, CAB). The next three participants randomized to Latin Square B (ABC, BAC, CBA). Subsequent randomisations will alternate between Latin Squares A and B each in random order.

All participants in Part B will receive the same formulation, no randomization is required. Based on the PK data from the first 2 treatment periods and the safety data from all 3 treatment periods in Part A, participants in Part B will receive either three active TRX-248 TS of 1 of the selected formulations from Part A, or three active TRX-248 TS formulation D (optimized within the parameters of 3 formulations tested in Part A).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/06/2025
Actual
Date of last participant enrolment
Anticipated
10/07/2025
Actual
Date of last data collection
Anticipated
5/09/2025
Actual
Sample size
Target
9
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 318568 0
Commercial sector/Industry
Name [1] 318568 0
Corsair Pharma, Inc.
Country [1] 318568 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Corsair Pharma, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 320967 0
None
Name [1] 320967 0
Address [1] 320967 0
Country [1] 320967 0
Other collaborator category [1] 283452 0
Commercial sector/Industry
Name [1] 283452 0
Novotech(Australia) Pty Limited
Address [1] 283452 0
Country [1] 283452 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317170 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 317170 0
Ethics committee country [1] 317170 0
Australia
Date submitted for ethics approval [1] 317170 0
05/03/2025
Approval date [1] 317170 0
31/03/2025
Ethics approval number [1] 317170 0
HREC/116529/Alfred-2025 (Local Reference: Project 149/25)

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 140230 0
Dr Arockiaa Philo ‘Aarthy’ Joseph
Address 140230 0
Nucleus Network, Level 5, Burnet Tower, 89 Commercial Road, Melbourne Victoria 3004.
Country 140230 0
Australia
Phone 140230 0
+61 03 8593 9801
Fax 140230 0
Email 140230 0
[email protected]
Contact person for public queries
Name 140231 0
Dr Joseph
Address 140231 0
Nucleus Network, Level 5, Burnet Tower, 89 Commercial Road, Melbourne Victoria 3004.
Country 140231 0
Australia
Phone 140231 0
+61 1800 243 733
Fax 140231 0
Email 140231 0
[email protected]
Contact person for scientific queries
Name 140232 0
Willemijn Passtoors
Address 140232 0
Novotech (Australia) Pty Ltd Level 19, 66 Goulburn Street, Sydney, NSW, 2000, Australia
Country 140232 0
Australia
Phone 140232 0
+61421883652
Fax 140232 0
Email 140232 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.