Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000646640
Ethics application status
Approved
Date submitted
12/06/2014
Date registered
18/06/2014
Date last updated
24/02/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of tretinoin capsule against the innovator tretinoin capsule conducted under fed conditions in healthy male volunteers
Scientific title
A single dose, randomized, blinded, bioequivalence study of a test formulation of tretinoin capsule in a 2 way crossover comparison against the innovator tretinoin capsule conducted under fed conditions in healthy male volunteers
Secondary ID [1] 284781 0
None
Universal Trial Number (UTN)
U1111-1157-1409
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bioequivalence study conducted in healthy volunteers comparing two formulations of tretinoin 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, tretinoin belongs to a class of medicines called retinoid. It is used to induce maturation of acute promyelocytic leukemia (APL) cells in culture. It is indicated for the induction of remission in patients with APL.
292157 0
Condition category
Condition code
Other 292491 292491 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 formulation of tretinoin (1 x 10 mg) on one occasion and the innovator formulation of tretinoin (1 x 10 mg) on one occasion with each dose seperated by a one week washout period. The intervention for this trial is the test formulation of tretinoin.

Each dose (1 x 10 mg) 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 the medication has been taken as directed.

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

Participants are required not to eat for 9.5 hours prior to breakfast and dosing and are required to fast for approximately 4 hours after receiving each dose. Participants will be provided with a standardised high fat content breakfast which they must start eating 30 minutes prior to dosing.

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

Participants will be confined at the Clinical Site for 10 hours prior to dosing to ensure compliance and will be monitored and for 11 hours after dosing.

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 10 hours prior to dosing.

Pre and post study laboratory tests will be completed to assess the healthy of participants along with HIV, Hepatitis and drugs of abuse testing.
Intervention code [1] 289571 0
Treatment: Drugs
Comparator / control treatment
Single dose, crossover study design whereby each participant receives the test formulation of tretinoin (1 x 10 mg) on one occasion and the innovator formulation of tretinoin (1 x 10 mg) on one occasion with each dose seperated by a one week washout period. The comparator/control for this trial is the innovator formulation of tretinoin.
Control group
Active

Outcomes
Primary outcome [1] 292353 0
To compare the bioavailability of tretinoin (as summarised by Cmax and AUC) for the formulation. All plasma samples will be assayed for tretinoin using one fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 292353 0
-1, -0.5, 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2.0, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10 and 11 hours
Secondary outcome [1] 308753 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] 308753 0
-1, -0.5, 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2.0, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10 and 11 hours
Secondary outcome [2] 308880 0
T1/2, the elimination half life will be determined by plasma sample analysis. T1/2 = 0.693/Kel where kel is the terminal elimination rate constant.
Timepoint [2] 308880 0
-1, 0.5, 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2.0, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 9, 10 and 11 hours

Eligibility
Key inclusion criteria
Healthy males
Aged between 18 and 55
Non-smoker
BMI between 18 and 33 inclusive
Normal, healthy individuals as determined by medical history, physical examination, ECG, blood pressure and laboratory tests
Able to provide written informed consent
Minimum age
18 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Females
Any history of recent recurrent attacks of bronchitis, asthma, migraine headaches
Concomitant drug therapy of any kind
Who have receievd an investigational compound or drug known to induce or inhibit liver enqymes within 60 days of the start of the study
History or family history of depression or other mental illness, epilepsy or seizures
Sensitivity to tretinoin any other similar class medicines, excipients of tretinoin
History of any conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
Who are sensitive to Vitamin A or food such as liver, which contain large quantities of Vitamin A.
Who might have an increased sensitivity to sunlight.
Who wear contact lenses.
Who are planning to start a family with 60 days of receiving the final dose.
Smoker (anyone who has smoked in the last 6 months)
History of alcohol or drug abuse or dependency
Participation in a drug study within 60 days of the start of the study or donated blood in the 60 days preceding the study.
Volunteers 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 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 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
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation list will be prepared using a computer program for a balanced two-way crossover design.
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
15/09/2014
Actual
15/09/2014
Date of last participant enrolment
Anticipated
Actual
24/09/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment outside Australia
Country [1] 6133 0
New Zealand
State/province [1] 6133 0
Otago

Funding & Sponsors
Funding source category [1] 289397 0
Commercial sector/Industry
Name [1] 289397 0
Douglas America Ltd
Country [1] 289397 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] 288079 0
None
Name [1] 288079 0
Address [1] 288079 0
Country [1] 288079 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291158 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 291158 0
Ministry of Health
1 the Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 291158 0
New Zealand
Date submitted for ethics approval [1] 291158 0
Approval date [1] 291158 0
10/06/2014
Ethics approval number [1] 291158 0
14/NTB/69

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test (new) formulation of 1 x 10 mg against the reference formulation (innovator brand of 1 x 10 mg tretinoin capsule) following oral administration of a single dose of 1 x 10 mg in healthy male subjects under fed 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 49134 0
Dr Noelyn Hung
Address 49134 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 49134 0
New Zealand
Phone 49134 0
+6434779669
Fax 49134 0
+6434779605
Email 49134 0
[email protected]
Contact person for public queries
Name 49135 0
Mrs Linda Folland
Address 49135 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 49135 0
New Zealand
Phone 49135 0
+6434779669
Fax 49135 0
+6434779605
Email 49135 0
[email protected]
Contact person for scientific queries
Name 49136 0
Dr Tak Hung
Address 49136 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 49136 0
New Zealand
Phone 49136 0
+6434779669
Fax 49136 0
+6434779605
Email 49136 0
[email protected]

No information has been provided regarding IPD availability


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.