Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12625000939493p
Ethics application status
Submitted, not yet approved
Date submitted
20/08/2025
Date registered
29/08/2025
Date last updated
29/08/2025
Date data sharing statement initially provided
29/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A pivotal study in healthy women comparing Mi-Gel® and amitriptyline gel applied topically for 6 consecutive days.
Scientific title
A pivotal bioequivalence study comparing amitriptyline in Mi-Gel® topical gel (containing amitriptyline 5mg/g and estriol 0.3mg/g) to Amitriptyline 5mg/g topical gel in healthy women in a multiple dose, open label, balanced, randomised, two-treatment, two period, two sequence, two-way crossover bioequivalence study under steady state conditions.
Secondary ID [1] 315137 0
None
Universal Trial Number (UTN)
U1111-1324-9561
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Vulvodynia 338561 0
Pudendal neuralgia 338562 0
Vestibulitis 338563 0
Dyspareunia 338564 0
Condition category
Condition code
Anaesthesiology 334865 334865 0 0
Pain management
Renal and Urogenital 334866 334866 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single-centre, multiple dose, open label, balanced, randomised, two-treatment, two-period, two-sequence, two-way crossover pivotal study with amitriptyline 5mg/g self applied to the vulva twice daily for 5 consecutive days and once on Day 6 separated by a washout period of 14 days in healthy women under steady state conditions.

The intervention for this trial is the test formulation of amitriptyline

The study medication will be self-applied in private at the In-patient facility at approximately 8 am on Study Day 1 and at the Out-patient facility on Study Days 2-5 and at home at approximately 8 pm on Study Days 1-4 of both study periods.

On the evening of Study Day 5 of each study period the participant is confined to our In-patient facility for a 1-night stay (about 25 hours on each occasion) for self-application of the study medication and Pharmacokinetic blood samples.

Participants will be monitored for adverse events throughout the study. A diary will completed on a daily basis to record a Vulval Irritation Questionnaire and any adverse events experienced.

Standard meals will be consumed at our In-Patient facility with no additional food intake allowed during confinement days. Pregnancy testing will be performed on Day 1 prior to dosing & alcohol breath testing, urine drugs of abuse will be performed upon each participant reporting to the In-patient facility on Day 5, 13 hours prior to dosing of each study period..

Pre and post study laboratory tests will be completed to assess the health of the participants along with drugs of abuse testing and pregnancy testing.

Adherence to the study protocol will be done by weighing the gel before and after use.
Intervention code [1] 331762 0
Treatment: Drugs
Comparator / control treatment
The comparator/control for this trial is the innovator formulation of Mi-Gel. containing amitriptyline 5mg/g and estriol 0.3mg/g self applied to the vulva twice daily for 5 consecutive days and once on Day 6.
Control group
Active

Outcomes
Primary outcome [1] 342494 0
The statistical objective is to compare the pharmacokinetic parameters of amitriptyline.
Timepoint [1] 342494 0
A pre-dose sample prior to each morning dose application on study days 1-5 of each period. On study day 6 and 27 the sampling intervals will be at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours after application.
Secondary outcome [1] 451039 0
Additional Pharmacokinetic (PK) of amitriptyline in plasma.
Timepoint [1] 451039 0
A pre-dose sample prior to each morning dose application on study days 1-5 of each period. On study day 6 and 27 the sampling intervals will be at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours after application.
Secondary outcome [2] 451040 0
To assess the occurrence of adverse events for the single-dose safety and tolerability of the formulations.
Timepoint [2] 451040 0
Continuously from consent until the end of the study
Secondary outcome [3] 451041 0
To investigate any symptoms and side effects of amitriptyline
Timepoint [3] 451041 0
Questionnaires will be administered at screening, baseline (pre-dose) and prior to each dose administration and at study exit.

Eligibility
Key inclusion criteria
Non-pregnant, assigned at birth females .
Aged between 18 and 65 on day of consent
BMI between 18.5 and 30.0
Non-smoker
Drug free as determined by a Urine Drugs Test
Normal, healthy individuals as determined by medical history, physical examination, ECG, vital signs and laboratory tests
Able to provide written informed consent in English
Able to adhere to all study restrictions and attend all study visits
Consent to GP being contacted if necessary
Minimum age
18 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Known history or presence of any clinically significant medical conditions
Any clinically significant abnormality at physical examination or clinically significant abnormal laboratory test results as determined by the Investigator.
Women who are pregnant or plan to become pregnant in the next 3 months, or lactating females.
History of genital herpes with >3 outbreaks per year or active non-HPV vaginal infection or vulval infections or irritations, thrush or lichen sclerosis.
Had an abortion or miscarriage within the 3 months prior to randomisation.
A known allergy, hypersensitivity, or intolerance to amitriptyline or Mi-Gel or its excipients.
History of significant alcohol abuse within one year prior to date of consent or regular use of alcohol within six months prior to the date of consent
History of significant drug abuse or dependency within one year prior to date of consent.
Participation in a clinical research study within 30 days prior to Study Day 1
Use of medication other than topical products without significant systemic absorption.
Prescription medication (except prescribed hormonal contraceptive) within 14 days prior to Study Day 1;
Currently taking any of these medications - Alfuzosin, Amiodarone, dronedarone, Ranolazine, Fusidic Acid, Colchicine, Astemizole, terfenadine, Lurasidone, Pimozide, Quetiapine, Dihydroergotamine, ergonovine, ergotamine, methylergonovine, Cisapride, Lovastatin, simvastatin, Avanafil, Sildenafil, Vardenafil, Oral midazolam, triazolam, St. John's wort.
Over-the-counter products and natural health products within 7 days prior to Study Day 1, with the exception of prescribed hormonal contraception which does not contain Estriol.
Donation of platelets or plasma within 30 days prior to Study Day 1.
Participants who are not surgically sterile, post-menopausal or who are sexually active and not using effective contraception for the prevention of pregnancy (i.e. prescribed hormonal contraceptives or other reliable method) for at least 14 days prior to Study Day 1 until 7 days after the Study Exit visit.
Participants of childbearing potential who use a hormonal contraceptive which contains Estriol.
Participants who have poor venous access or cannot tolerate venepuncture, IV cannula insertion or who have a fear of needles or blood
Any participant for whom the Investigator believes, for any reason, inclusion would not be an acceptable risk.
Any clinically significant illness in the 30 days prior to Study Day 1.

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)
Each participant will be given a 3 digit screening number and a 2 digit subject number. The screening number will be issued once the participant has given written consent to participate in the study and the two digit subject number (randomisation number) after acceptance into the study. Sequence generation will be by using a simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
13/09/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 27298 0
New Zealand
State/province [1] 27298 0
Otago

Funding & Sponsors
Funding source category [1] 319714 0
Commercial sector/Industry
Name [1] 319714 0
Aspen Pharmacare Australia Pty Ltd
Country [1] 319714 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
Country
New Zealand
Secondary sponsor category [1] 322222 0
None
Name [1] 322222 0
Address [1] 322222 0
Country [1] 322222 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 318267 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 318267 0
Ethics committee country [1] 318267 0
New Zealand
Date submitted for ethics approval [1] 318267 0
08/08/2025
Approval date [1] 318267 0
Ethics approval number [1] 318267 0
2025 FULL 23619

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

Contacts
Principal investigator
Name 143642 0
Dr Noelyn Hung
Address 143642 0
Zenith Technology Corp Ltd 156 Frederick Street, (PO Box 1777) Dunedin 9016
Country 143642 0
New Zealand
Phone 143642 0
+64 21 48 21 48
Fax 143642 0
Email 143642 0
[email protected]
Contact person for public queries
Name 143643 0
Ms Linda Folland
Address 143643 0
Zenith Technology Corp Ltd 156 Frederick Street, (PO Box 1777) Dunedin 9016
Country 143643 0
New Zealand
Phone 143643 0
+64 3 477 9669
Fax 143643 0
Email 143643 0
[email protected]
Contact person for scientific queries
Name 143644 0
Dr Tak Hung
Address 143644 0
Zenith Technology Corp Ltd 156 Frederick Street, (PO Box 1777) Dunedin 9016
Country 143644 0
New Zealand
Phone 143644 0
+64 3 477 9669
Fax 143644 0
Email 143644 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.