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Trial registered on ANZCTR


Registration number
ACTRN12615000281594
Ethics application status
Approved
Date submitted
19/03/2015
Date registered
25/03/2015
Date last updated
21/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of bosentan film-coated tablet against the innovator bosentan film-coated tablet conducted under fasting conditions in healthy male volunteers
Scientific title
A single dose, randomized, blinded, bioequivalence study of a test formulation of bosentan film-coated tablet in a 2 way crossover comparison against the innovator bosentan film-coated tablet conducted under fasting conditions in healthy male volunteers
Secondary ID [1] 286382 0
None
Universal Trial Number (UTN)
U1111-1167-9079
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bioequivalence study conducted in healthy volunteers comparing two formulations of bosentan 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, bosentan is an endothelin receptor antagonist that belongs to a class of highly substituted pyrimidine derivatives and is indicated for the treatment of idiopathic pulmonary arterial hypertension, familial pulmonary arterial hypertension, pulmonary arterial hypertension associated with schleroderma or pulmonary arterial hypertension assocated with congenital or systemic to pulmonary shunts including Eisenmenger's physiology.
294525 0
Condition category
Condition code
Other 294831 294831 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 bosentan (1 x 125 mg) on one occasion and the innovator formulation of bosentan (1 x 125 mg) on one occasion with each dose seperated by a two week washout period. The intervention for this trial is the test formulation of bosentan.

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 before receiving each dose and to fast for approximately 4 hours after 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 12 hours prior to dosing to ensure compliance and will be monitored and for 24 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 12 hours prior to dosing.

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

Each dose (1 x 125 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.
Intervention code [1] 291448 0
Treatment: Drugs
Comparator / control treatment
Single dose, crossover study design whereby each participant receives the test formulation of bosentan (1 x 125 mg) on one occasion and the innovator formulation of bosentan (1 x 125 mg) on one occasion with each dose seperated by a two week washout period. The comparator/control for this trial is the innovator formulation of bosentan.
Control group
Active

Outcomes
Primary outcome [1] 294596 0
To compare the bioavailability of bosentan (as summarised by Cmax and AUC) for the formulation. All plasma samples will be assayed for melatonin using one fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 294596 0
0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours
Secondary outcome [1] 313690 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] 313690 0
0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7, 8, 10, 12, 16 and 24 hours

Eligibility
Key inclusion criteria
Healthy male
Aged between 18 and 45
Non-smoker
BMI between 19 and 30 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
45 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Any history of recent recurrent attacks of bronchitis, asthma, migraine headaches
Concomitant drug therapy of any kind
Who have received an investigational compound or drug known to induce or inhibit liver enzymes within 60 days of the start of the study
Sensitivity to bosentan or any other similar class of medicines, or the excipients of bosentan
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 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.
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 subject 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)
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] 6760 0
New Zealand
State/province [1] 6760 0
Otago

Funding & Sponsors
Funding source category [1] 290954 0
Commercial sector/Industry
Name [1] 290954 0
Novotech (Australia) Pty Ltd
Address [1] 290954 0
Level 3, 235 Pyrmont Street
Pyrmont
NSW 2009
Country [1] 290954 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corp Ltd
Address
156 Frederick Street
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 289636 0
None
Name [1] 289636 0
Address [1] 289636 0
Country [1] 289636 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292552 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 292552 0
Ministry of Health
Freyberg Building
20 Aitken Street
Wellington 6011
Ethics committee country [1] 292552 0
New Zealand
Date submitted for ethics approval [1] 292552 0
05/03/2015
Approval date [1] 292552 0
18/03/2015
Ethics approval number [1] 292552 0
15/STH/34

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test (new) formulation of 1 x 125 mg bosentan film-coated tablet against the reference formulation (innovator brand of 1 x 125 mg bosenten film-coated tablet) following oral administration of a single dose of 1 x 125 mg 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 55902 0
Dr Noelyn Hung
Address 55902 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 55902 0
New Zealand
Phone 55902 0
+6434779669
Fax 55902 0
+6434779605
Email 55902 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 55903 0
Mrs Linda Folland
Address 55903 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 55903 0
New Zealand
Phone 55903 0
+6434779669
Fax 55903 0
+6434779605
Email 55903 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 55904 0
Dr Cheung-Tak Hung
Address 55904 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 55904 0
New Zealand
Phone 55904 0
+6434779669
Fax 55904 0
+6434779605
Email 55904 0
tak.hung@zenithtechnology.co.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary