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Trial registered on ANZCTR


Registration number
ACTRN12615001083583
Ethics application status
Approved
Date submitted
8/10/2015
Date registered
14/10/2015
Date last updated
14/05/2019
Date data sharing statement initially provided
14/05/2019
Date results information initially provided
14/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment in healthy male volunteers under fasting conditions of the absorption and pharmacokinetics of 3 generic formulations of isotretinoin capsules against the innovator isotretinoin capsule in a pilot study
Scientific title
A single dose, randomized, blinded, 4 way crossover pilot pharmacokinetic study of 3 test formulations of isotretinoin capsules against the innovator isotretinoin capsule conducted under fasting conditions in healthy male volunteers
Secondary ID [1] 287630 0
None
Universal Trial Number (UTN)
U1111-1174-8126
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pilot study conducted in healthy volunteers comparing four formulations of isotretinoin with no health condition or problem studied.

Although this study is being conducted in healthy volunteers who are not being treated for the condition to which the medicine is used, isotretinoin is a medicine that is used to treat severe forms of acne.
296445 0
Condition category
Condition code
Other 296710 296710 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, crossover study design whereby each participant receives the test formulations of isotretinoin, 1 x 40 mg capsule (T1, T2 and T3) on one occasion each and the innovator formulation of isotretinoin, 1 x 40 mg capsule on one occasion. The intervention for this trial is the test formulations of isotretinoin.

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 each dose and to fast for approximately 4 hours after each dose.
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. Alcohol breath testing will be performed upon each participant reporting to the Clinical Site 12 hours prior to dosing.

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

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.

Each dose is separated by a one week washout period.
Intervention code [1] 293031 0
Treatment: Drugs
Comparator / control treatment
Single dose, crossover study whereby each participant receives the test formulation of isotretinoin (1 x 40 mg) on three occasions and the innovator formulation of isotretinoin (1 x 40 mg) on one occasion with each dose separated by a one week washout period. The comparator/control for this trial is the innovator formulation of isotretinoin.
Control group
Active

Outcomes
Primary outcome [1] 296322 0
To evaluate the pharmacokinetics (as summarised by Cmax and AUC) of the three test formulations relative to that of the reference formulation. All plasma samples will be assayed for isotretinoin using one fully validated LC/MS/MS method. Validation will be conducted to comply with FDA guidelines.
Timepoint [1] 296322 0
0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 10.0, 12.0, 16.0, 20.0, 24.0, 32.0, 48.0, 56.0 and 72 hours after dosing.
Secondary outcome [1] 318147 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] 318147 0
0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0, 9.0, 10.0, 12.0, 16.0, 20.0, 24.0, 32.0, 48.0, 56.0 and 72 hours after dosing.

Eligibility
Key inclusion criteria
Healthy males
Aged between 18 and 55 years
Non-smoker
BMI greater than or equal to 19 and less than 30 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 information consent
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Females
Concomitant drug therapy of any kind
History of depression or other mental illness, or a history of epilepsy or seizures
History of conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
History of alcohol or drug abuse or dependency
Sensitivities to Vitamin A or food such as liver
Participation in a drug study within 60 days of the start of the study or undertaking to donate blood within 60 days after the completion of the study
Sensitivities to isotretinoin, its excipients or any other retinoids
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, B, C and D. The identification of each treatment will only be known to the Managing Director and Section Head - Trials and Regulatory Affairs or their delegate. Randomisation will be performed using a randomisation table created by computer software (i.e. computerised sequence generation).
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.
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)
Pharmacokinetics
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] 7215 0
New Zealand
State/province [1] 7215 0
Otago

Funding & Sponsors
Funding source category [1] 292192 0
Commercial sector/Industry
Name [1] 292192 0
Douglas America Ltd
Address [1] 292192 0
Central Park Drive
PO Box 45-027
Auckland 0610
Country [1] 292192 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corp Ltd
Address
156 Frederick Street
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 290870 0
None
Name [1] 290870 0
Address [1] 290870 0
Country [1] 290870 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293665 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 293665 0
Ministry of Health
Freyberg Building
20 Aitken Street
Wellington 6011
Ethics committee country [1] 293665 0
New Zealand
Date submitted for ethics approval [1] 293665 0
23/09/2015
Approval date [1] 293665 0
23/10/2015
Ethics approval number [1] 293665 0
15/NTA/140

Summary
Brief summary
The objective of this study is to evaluate the pharmacokinetics of three test formulations of isotretinoin 40 mg capsule against the reference formulation (innovator brand of 40 mg isotretinoin capsule) following administration of a single oral dose in healthy male subjects under fasting conditions.
Trial website
Trial related presentations / publications
No presentations or citations available. Final CSR provided to Sponsor Company for Registration Purposes
Public notes

Contacts
Principal investigator
Name 60890 0
Dr Noelyn Hung
Address 60890 0
Zenith Technology Corporation Limited
156 Frederick Street
Dunedin 9016
Country 60890 0
New Zealand
Phone 60890 0
+6434779669
Fax 60890 0
+6434779605
Email 60890 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 60891 0
Mrs Linda Folland
Address 60891 0
Zenith Technology Corporation Limited
156 Frederick Street
Dunedin 9016
Country 60891 0
New Zealand
Phone 60891 0
+6434779669
Fax 60891 0
+6434779605
Email 60891 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 60892 0
Dr Cheung-Tak Hung
Address 60892 0
Zenith Technology Corporation Limited
156 Frederick Street
Dunedin 9016
Country 60892 0
New Zealand
Phone 60892 0
+6434779669
Fax 60892 0
+6434779605
Email 60892 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