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Trial registered on ANZCTR


Registration number
ACTRN12620000825954
Ethics application status
Approved
Date submitted
31/07/2020
Date registered
18/08/2020
Date last updated
9/07/2021
Date data sharing statement initially provided
18/08/2020
Date results information initially provided
9/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule against the innovator 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule conducted under fed conditions in healthy volunteers.
Scientific title
A single dose, randomized, blinded, pharmacokinetic study of a generic formulation of 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule in a 2 way crossover comparison against the innovator 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule conducted under fed conditions in healthy volunteers.
Secondary ID [1] 301702 0
None
Universal Trial Number (UTN)
U1111-1243-9966
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid is a member of a subclass of retinoids. It is indicated for the treatment of skin manifestations of advanced stage cutaneous T-cell lymphoma (CTCL). 318156 0
Condition category
Condition code
Cancer 316176 316176 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, crossover study design whereby each participant receives the test formulation of
1 x 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule on one occasion and the innovator formulation of 1 x 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule on one occasion with each dose separated by a one week washout period. The intervention for this trial is the test capsule formulation.

No water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with each dose).

Participants are required not to eat for 10 hours before receiving a standardised high fat content meal and to fast for approximately 4 hours after each dose. The high fat content meal will consist of 2 eggs fried in butter, 2 slices of white toast, 120g hash brown patties, 2 slices of bacon and 240mL of whole milk comprising of approximately 800 to 1000 calories (approximately 50% of total caloric content of the meal derived from fat). This test meal will derive approximately 150, 250, and 500 600 calories from protein, carbohydrate, and fat, respectively.

Bathroom visits will be supervised to ensure no unauthorized water or food intake and for personal safety.

Participants will be confined at the Clinical Site for 12 hours prior to dosing to ensure compliance and for 24 hours after dosing.

Participants will be monitored for adverse events throughout the study.

Standard meals will be consumed at the Clinical Site with no additional food intake allowed.
The actual meals provided will be determined based on the menu in operation at the time of study conduct. As a guide the lunch and dinner meals will consist of a medium sized serving of meat, vegetables and dessert with fruit available in the evening. A vegetarian option may be available. The meals will not contain any chocolate or citrus products.

Alcohol breath testing and dipstick drugs of abuse tests will be performed upon each participant reporting to the clinical site 12 hours prior to dosing.

Screening procedures including laboratory tests and medical examinations will be completed to assess the health of the participants. Study exit procedures will be completed within one week after receiving the last dose.

Each dose will be taken orally with 240 ml of water at ambient temperature. Medication must be swallowed whole and a mouth check will be conducted to ensure that the medication has been taken as directed.
Intervention code [1] 318008 0
Treatment: Drugs
Comparator / control treatment
Single dose, crossover study whereby each participant receives the test formulation 1 x 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule on one occasion and the innovator formulation of 1 x 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule on one occasion with each dose separated by a one week washout period. The comparator/control for this trial is the innovator formulation.
Control group
Active

Outcomes
Primary outcome [1] 324356 0
To evaluate the pharmacokinetics (as summarised by Cmax and AUC) of the test formulation relative to that of the reference formulation. All plasma samples will be assayed for
4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid using one fully validated LC/MS/MS method. Validation will be conducted to comply with FDA guidelines.
Timepoint [1] 324356 0
Two pre-dose samples at -30 and -0 and at 1, 1.5, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post dosing.
Secondary outcome [1] 384430 0
Time to maximum peak concentration (Tmax) will be determined by plasma sample analysis. Tmax will be the time where the maximum concentration occurred in the sample points.
Timepoint [1] 384430 0
Two pre-dose samples at -30 and -0 and at 1, 1.5, 2, 2.33, 2.67, 3, 3.33, 3.67, 4, 4.5, 5, 6, 7, 8, 10, 12, 14, 16, 20 and 24 hours post dosing.

Eligibility
Key inclusion criteria
Healthy males
Aged between 18 and 55 years
Non-smoker
BMI greater than or equal to 18.5 and less than 29.9 inclusive
Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests
Drug free as determined by urine drug testing
Able to comply with the study restrictions
Able to provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Clinically significant medical conditions
History of conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
History of alcohol or drug abuse or dependency
Participation in a drug study within 60 days of the start of the study
Sensitivitie to the study drug or excipients
Individuals for whom the Clinical Investigator believes, for any reason, that participation would not be an acceptable risk

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 labeled as Formulation A and B. The identification of each treatment will only be known to the Managing Director and Section Head - Trials and Regulatory Affairs or their delegate.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Each participant will be identified by 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 study number (randomisation number) after acceptance into the study. Randomization will be performed using a randomisation table created by computer software (i.e. computerized sequence generation).
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
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Bio-equivalence
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 22721 0
New Zealand
State/province [1] 22721 0
Otago

Funding & Sponsors
Funding source category [1] 306139 0
Commercial sector/Industry
Name [1] 306139 0
Douglas Pharmaceuticals Ltd
Address [1] 306139 0
Central Park Drive
PO Box 45-027
Auckland 0610
Country [1] 306139 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
PO Box 1777
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 306607 0
None
Name [1] 306607 0
Address [1] 306607 0
Country [1] 306607 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306356 0
Northern A Health & Disability Ethics Committee
Ethics committee address [1] 306356 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6145
Ethics committee country [1] 306356 0
New Zealand
Date submitted for ethics approval [1] 306356 0
02/12/2019
Approval date [1] 306356 0
30/01/2020
Ethics approval number [1] 306356 0
19/NTA/172

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test (new) formulation
75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule relative to that of the reference formulation following oral administration of a single dose of 75 mg 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2- naphthalenyl) ethenyl] benzoic acid capsule in healthy subjects under fed conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103598 0
Dr Noelyn Hung
Address 103598 0
Zenith Technology Corp Ltd
PO Box 1777,
Dunedin 9054
Country 103598 0
New Zealand
Phone 103598 0
+64 3 477 9669
Fax 103598 0
+64 3 477 9605
Email 103598 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 103599 0
Mrs Linda Folland
Address 103599 0
Zenith Technology Corp Ltd
PO Box 1777,
Dunedin 9054
Country 103599 0
New Zealand
Phone 103599 0
+64 3 477 9669
Fax 103599 0
+64 3 477 9605
Email 103599 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 103600 0
Dr Tak Hung
Address 103600 0
Zenith Technology Corp Ltd
PO Box 1777,
Dunedin 9054
Country 103600 0
New Zealand
Phone 103600 0
+64 3 477 9669
Fax 103600 0
+64 3 477 9605
Email 103600 0
tak.hung@zenithtechnology.co.nz

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 other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary