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Trial registered on ANZCTR


Registration number
ACTRN12620000191998
Ethics application status
Approved
Date submitted
13/02/2020
Date registered
19/02/2020
Date last updated
19/02/2020
Date data sharing statement initially provided
19/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets against the innovator (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets conducted under fasting conditions in healthy male and female volunteers
Scientific title
A single dose, blinded, balanced, randomised, two-treatment, four period, two sequence, four-way fully replicated crossover bioequivalence study comparing 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets with 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets in healthy male and female subjects under fasting conditions.
Secondary ID [1] 300506 0
Nil
Universal Trial Number (UTN)
U1111-1234-9491
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
(2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid is used for the treatment of management of demonstrated thyroid hormone deficiency. 316198 0
Condition category
Condition code
Metabolic and Endocrine 314488 314488 0 0
Thyroid disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, two-treatment, four-period, two-sequence, fully replicated crossover, bioequivalence design whereby each participant receives the test formulation of 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets on two occasions and the innovator formulations of 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets on two other occasions with all four occasions being separated by a 6 week washout period. The intervention for this trial is the test formulation of 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablet.

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 10 hours prior to dosing. Subjects are required to fast for approximately 4 hours after receiving each dose. 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 for 24 hours.

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 health of participants.

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 the medication has been taken as directed.
Intervention code [1] 316817 0
Treatment: Drugs
Comparator / control treatment
Single dose, two-treatment, four-period, two-sequence, fully replicated crossover, bioequivalence design whereby each participant receives the test formulation of 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets on two occasions and the innovator formulations of 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets on two occasions with each dose separated by a six week washout period. The intervention for this trial is the test formulation of 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablet.
Control group
Active

Outcomes
Primary outcome [1] 322817 0
The primary outcome is to compare the bioavailability of (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid (as summarised by Cmax and AUC) for all formulations. All plasma samples will be assayed for (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid using one fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 322817 0
30, 15 and 5 mins pre-dose and at 0.5, 1, 1.5, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dosing.
Secondary outcome [1] 379881 0
The secondary outcome is measuring Time to maximum peak concentration (Tmax) in plasma for (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid combined in one assay. Tmax will be the time where the maximum concentration occurred in the sample points.
Timepoint [1] 379881 0
30, 15 and 5 mins pre-dose and at 0.5, 1, 1.5, 2, 2.33, 2.67, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post dosing.

Eligibility
Key inclusion criteria
Healthy males and females
Aged between 18 and 55
Non-smoker
BMI between 18.5 and 32 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
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any history of recent recurrent attacks of bronchitis, asthma, migraine headaches, hypothyroidism, hyperthyroidism and/or cardiovascular disorders.
Concomitant drug therapy of any kind
Sensitivity to any of the medicines or ingredients
History of any conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
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 30 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 four-way fully replicated 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
Not yet recruiting
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] 22344 0
New Zealand
State/province [1] 22344 0
Otago

Funding & Sponsors
Funding source category [1] 304923 0
Commercial sector/Industry
Name [1] 304923 0
Southern Cross Pharma Pty Ltd
Address [1] 304923 0
Suite 5, 118 Church Street
Hawthorn
Vic 3122
Country [1] 304923 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
156 Frederick St
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 305272 0
None
Name [1] 305272 0
Address [1] 305272 0
Country [1] 305272 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305331 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 305331 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 305331 0
New Zealand
Date submitted for ethics approval [1] 305331 0
13/06/2019
Approval date [1] 305331 0
10/07/2019
Ethics approval number [1] 305331 0
19/CEN/102

Summary
Brief summary
The objective of this study is to evaluate bioequivalence by comparing the rate and extent of absorption of the test formulation, 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets relative to that of the reference formulations, 3 x 200 mcg (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid tablets following oral administration of a single dose to healthy male and female subjects under fasting conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100026 0
Dr Noelyn Hung
Address 100026 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 100026 0
New Zealand
Phone 100026 0
+64 3 477 9669
Fax 100026 0
+6434779605
Email 100026 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 100027 0
Mrs Linda Folland
Address 100027 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 100027 0
New Zealand
Phone 100027 0
+64 3 477 9669
Fax 100027 0
+6434779605
Email 100027 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 100028 0
Dr Tak Hung
Address 100028 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 100028 0
New Zealand
Phone 100028 0
+64 3 477 9669
Fax 100028 0
+6434779605
Email 100028 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
No Results