Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001003662
Ethics application status
Approved
Date submitted
6/09/2023
Date registered
13/09/2023
Date last updated
18/08/2024
Date data sharing statement initially provided
13/09/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pivotal in vivo bioequivalence study comparing two formulations of 9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate cream applied to the skin in healthy male and female volunteers.
Scientific title
A pivotal in vivo bioequivalence study comparing two formulations of 9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate cream using the appropriate dose duration (ED50) calculated from the Pilot dose duration-response study, using healthy male and female volunteers who meet the responder and detector criteria.
Secondary ID [1] 310551 0
None
Universal Trial Number (UTN)
U1111-1294-9940
Trial acronym
Linked study record
This study is linked to ACTRN12623000887673 which determined the time points for this full pivotal bioequivalence study.

Health condition
Health condition(s) or problem(s) studied:
9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate cream is indicated for the topical treatment of eczema and psoriasis in children and adults. 331383 0
Condition category
Condition code
Skin 328132 328132 0 0
Dermatological conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A multiple dose study design whereby each participant receives 10 mg (5mg/cm2) per site of the test formulation of 9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate 0.5 mg/g (0.05% w/w) cream and 10 mg (5mg/cm2) per site of the innovator formulation of 9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate 0.5 mg/g (0.05% w/w) cream. The composition of the test and innovator formulations will be the same except for the excipients of each formulation.

The intervention for this trial is the test formulation of 0.5 mg/g (0.05% w/w) 9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate cream.

Subjects will be healthy subjects who have shown a vasoconstriction response to a single dose of 9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate 0.5 mg/g (0.05% w/w) cream

The test and reference ointment will be applied to pre-allocated sites at times determined from the pilot study results (ACTRN12623000887673p).
ED50 (optimal dose duration)
D1 (Shorter dose duration reference listed drug calibrator)
D2 (Longer dose duration reference listed drug calibrator)

The cream is then removed from all sites 5 hours after the first application and the Chromameter measurements for the pharmacodynamic responses of the topical corticosteroid will be carried out at 0, 2, 4, 6, 19 and 24 hours following removal.

There will be 16 sites in total (8 on each arm whereby 6 sites will be treated with the test or reference cream and 2 sites will be untreated control sites).

All application times will be recorded and checked in individual subjects Case Report Forms.

Cream is applied by a trained staff member using pre-filled applicators.

Subjects who meet the inclusion and exclusion criteria will be included in this study. Pre and post study laboratory tests will be performed along with an ECG and medical evaluation. A follow up visit will also be completed to assess for safety.
Intervention code [1] 326947 0
Treatment: Drugs
Intervention code [2] 326948 0
Treatment: Other
Comparator / control treatment
Two sites per arm are untreated.
Control group
Active

Outcomes
Primary outcome [1] 336005 0
To compare the in vivo bioequivalence of two formulations of 9-fluoro-11ß-hydroxy- 16ß-methyl-3,20-dioxopregna- 1,4-diene-17,21-diyl dipropanoate cream (as summarised by AUEC (Area Under the Effect Curve)) using vasoconstriction. Blanching will be evaluated objectively using a Minolta CR30 Chromameter. The values will be used to measure the degree of colour change of each treatment site using a formulation that will be calculated and plotted against time.
Timepoint [1] 336005 0
Cream is applied at various times to 6 sites per arm and assessed at each evaluation time of 0, 2, 4, 6, 19 and 24 hours after cream removal.
Secondary outcome [1] 426455 0
Safety of the two formulations will be assessed throughout the study days by observing the skin and asking participants if they are experiencing any side effects.
Timepoint [1] 426455 0
Assessed at each evaluation time of 0, 2, 4, 6, 19 and 24 hours after cream removal.

Eligibility
Key inclusion criteria
Males or females
In good general health
Show a vasoconstriction response to a single dose of Advantan Fatty Ointment
Aged between 18-55 years of age inclusive
BMI between 18 and 33 inclusive
Laboratory tests within normal ranges or assessed not significant by the Clinical Investigator
Normal ECG
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Clinically significant hypertension or circulatory disease and any clinically significant illness during the last four weeks prior to the entry into this study.
Caffeine intake greater than 500 mg per day prior to this study.
Who have been on a special diet, especially a low salt and/or fluid diet, during the 2 weeks prior to the first study day.
Use of topical Dermatologic drug therapy on ventral forearms.
Adverse reactions to topical or systemic corticosteroids.
Who require shaving of the ventral forearms.
Use of any vasoactive medication, prescription or over the counter that could modulate blood flow.
Use of any prescription medication within 2 weeks preceding entry into the study
Any obvious difference in skin colour between arms or any scarring on the forearms.
Females who are pregnant or lactating
Significant medical condition that could in the Investigator's opinion interfere with the study, or put the subject at significant risk
Participation in any drug or medical device study within 30 days of entering this study

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)
All formulations will be labelled as Formulation A and B. The identification of each treatment will only be known to the Managing Director and the Section Head - Trials and Regulatory Affairs.

Each participant will be identified by a 3 digit screening number which is determined by the order in which the participants give consent, ie the 1st participant to give consent is allocated 001. and a 2 digit subject number which is determined by simple randomisation using a computer generated true random number generator at www.random.org. The screening number will be issued once the participant has given written consent to participate in the study and the two digit subject number will be issued after acceptance into the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using a randomisation table created by computer software (i.e. computerised sequence generation).

The Randomization Scheme is computer generated by Zenith and as such, treatment sequences are randomly assigned to each subject number.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
This is a single period, two treatment study where each subject has ointment applied at time points determined by the Pilot Study (ACTRN12623000887673) e.g. receives 2 test and 4 reference doses on each arm as well as 2 blank sites per arm.
Phase
Phase 1
Type of endpoint/s
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/09/2023
Actual
12/09/2023
Date of last participant enrolment
Anticipated
Actual
1/11/2023
Date of last data collection
Anticipated
Actual
2/11/2023
Sample size
Target
90
Accrual to date
Final
90
Recruitment outside Australia
Country [1] 25756 0
New Zealand
State/province [1] 25756 0
Otago

Funding & Sponsors
Funding source category [1] 314754 0
Commercial sector/Industry
Name [1] 314754 0
Nova Chem Australasia Pty Ltd
Country [1] 314754 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
156 Frederick Street,Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 316737 0
None
Name [1] 316737 0
Address [1] 316737 0
Country [1] 316737 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313762 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 313762 0
Ethics committee country [1] 313762 0
New Zealand
Date submitted for ethics approval [1] 313762 0
11/07/2023
Approval date [1] 313762 0
04/08/2023
Ethics approval number [1] 313762 0
2023 FULL 18330

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

Contacts
Principal investigator
Name 129282 0
Dr Noelyn Hung
Address 129282 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 129282 0
New Zealand
Phone 129282 0
+64 21 482 148
Fax 129282 0
Email 129282 0
[email protected]
Contact person for public queries
Name 129283 0
Linda Folland
Address 129283 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 129283 0
New Zealand
Phone 129283 0
+6434779669
Fax 129283 0
Email 129283 0
[email protected]
Contact person for scientific queries
Name 129284 0
Tak Hung
Address 129284 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 129284 0
New Zealand
Phone 129284 0
+6434779669
Fax 129284 0
Email 129284 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
All data will be compiled into a final report that is the property of the sponsor company. All participant data will be provided in summary format and result of the study only will be reported


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.