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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]

PRO-CLNP1-001

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Pulmonary Arterial Hypertension

Condition category

Condition code

Cardiovascular

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]

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]

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]

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]

Timepoint [2]

Secondary outcome [1]

To assess the overall safety and tolerability of TRX-248 TS formulations and matching placebo in healthy female volunteers during Part A.

Assessment method [1]

- Clinical laboratory assessments (hematology, serum chemistry and urinalysis), - Vital signs (body temperature using a tympanic thermometer, heart rate, respiratory rate, systolic and diastolic blood pressure assessed using a vital signs machine), electrocardiogram (ECG), physical examination findings, specific AEs, reported AEs and serious adverse events (SAEs). - Orthostatic and routine vital signs (body temperature using a tympanic thermometer, heart rate, respiratory rate, systolic and diastolic blood pressure assessed using a vital signs machine) - Multiple electrocardiograms will be performed during the 24 hour treatment period (ECG), physical examination findings, specific AEs, reported AEs and serious adverse events (SAEs). The completed nonclinical studies with TRX-248 showed no additional adverse effects when delivered via the transdermal route. The observed local reactions at the application site in animal studies were skin irritation, redness, edema, discoloration, and occasional blister/scabbing. These reactions were mostly mild to moderate and self-resolving within ~3-7 days and occasionally ~2 weeks. - Known adverse events associated with Treprostinil (the TRX-248 prodrug will convert to Treprostinil in the body) include headache, nausea, diarrhea, jaw pain. - Each TS application site (both active and placebo) will be monitored using both a study staff observed finding of skin appearance (8 point scale) and other observed effects (6 point scale) and reported participant discomfort by the participant as to nature and severity of discomfort (burning, itching, pain, other). Scores will be recorded. - Abnormal laboratory findings (e.g., serum chemistry, hematology) or other abnormal assessments (e.g., ECGs, vital signs) that are judged by the Investigator as clinically significant will be recorded as AEs or SAEs. Clinically significant abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen following the start of the study will be reported as AEs or SAEs. - Data will not be linked to medical records. Study data will be entered into a database by site staff.

Timepoint [1]

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]

To assess the safety and tolerability when multiple TRX-248 systems are applied during Part B

Timepoint [2]

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Corsair Pharma, Inc.

Address [1]

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Corsair Pharma, Inc.

Address

Country

United States of America

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Commercial sector/Industry

Name [1]

Novotech(Australia) Pty Limited

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Hospital Ethics Committee

Ethics committee address [1]

https://www.alfredhealth.org.au/research/ethics-research-governance

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/03/2025

Approval date [1]

31/03/2025

Ethics approval number [1]

HREC/116529/Alfred-2025 (Local Reference: Project 149/25)

Summary

Brief summary

This is a Phase 1, open-label, placebo-controlled, randomized crossover study evaluating the pharmacokinetics (PK), safety, tolerability, and adhesion performance of multiple formulations of the TRX-248 transdermal system (TS) in healthy female volunteers.

The study consists of two parts:

Part A: Subjects receive single doses of three different TRX-248 formulations in a crossover design, with PK and safety assessments after each 24-hour application.

Part B: Based on Part A results, one optimized formulation is selected for further evaluation, where subjects receive either three patches of the selected formulation from Part A or a newly optimized Formulation D.
The TRX-248 Transdermal System is expected to provide the convenience of a once-daily needle-free delivery system, steady and continuous delivery of treprostinil, which provides optimal efficacy and safety.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Arockiaa Philo ‘Aarthy’ Joseph

Address

Nucleus Network, Level 5, Burnet Tower, 89 Commercial Road, Melbourne Victoria 3004.

Country

Australia

Phone

+61 03 8593 9801

Fax

[email protected]

Contact person for public queries

Name

Dr Joseph

Address

Nucleus Network, Level 5, Burnet Tower, 89 Commercial Road, Melbourne Victoria 3004.

Country

Australia

Phone

+61 1800 243 733

Fax

[email protected]

Contact person for scientific queries

Name

Willemijn Passtoors

Address

Novotech (Australia) Pty Ltd Level 19, 66 Goulburn Street, Sydney, NSW, 2000, Australia

Country

Australia

Phone

+61421883652

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

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.

Trial Review

Documents added manually

Documents added automatically