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Trial registered on ANZCTR


Trial ID
ACTRN12613000650796
Ethics application status
Approved
Date submitted
5/06/2013
Date registered
12/06/2013
Date last updated
10/10/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of asenapine sublingual tablet against the innovator asenapine sublingual tablet conducted under fasting conditions in healthy male and female volunteers
Scientific title
A open-label, balanced, randomised, single-dose, two-treatment, three-period, three-sequence, oral bioequivalence study of asenapine sublingual tablets in a three-way crossover, partial replicate, reference scaled, comparison against the innovator asenapine sublingual tablets conducted under fasting conditions in healthy male and female volunteers
Secondary ID [1] 282618 0
None
Universal Trial Number (UTN)
U1111-1142-8145
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bioequivalence study on asenapine formulations.

289309 0
Schizophrenia in adults 289356 0
Condition category
Condition code
Other 289646 289646 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Mental Health 289692 289692 0 0
Schizophrenia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, crossover over study design whereby each participant receives the test formulation of asenapine sublingual (1 x 10 mg) on one occasion and the innovator formulation of asenapine sublingual (1 x 10 mg) on two occasions with each dose seperated by a one week washout period. The intervention for this trial is the test formulation of asenapine.

Each dose (1 x 10 mg) will be placed under the subjects tongue. Subjects will be instructed not to chew or swallow the tablet but to allow it to dissolve completely. Investigators will complete a mouth check at frequent intervals to ensure that the medication has been taken as directed and is fully dissolved.

An allergy scratch test will be carried out the night prior to dosing. Subjects are required to consume 200ml of water one hour prior to dosing. At least 10 minutes prior to dosing subjects will be asked to void their bladder and the site of the scratch test will be checked to ensure that no drug sensitivity problems have been developed. Participants are required not to eat for 10 hours before receiving each dose and 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 can 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 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. An allergy scratch test to determine sensitivity will be carried out during medical screening and prior to receving each asenapine dose.
Intervention code [1] 287284 0
Treatment: Drugs
Comparator / control treatment
Single dose, two treatment, three-way crossover over study design whereby each participant receives the test formulation of asenapine sublingual (1 x 10 mg) on one occasion and the innovator formulation of asenapine sublingual (1 x 10 mg) on two occasions with each dose seperated by a one week washout period. The comparator/control for this trial is the innovator formulation of asenapine.
Control group
Active

Outcomes
Primary outcome [1] 289727 0
To compare the bioavailability of asenapine (as summarised by Cmax and AUC) for the two formulations. If the within-subject variability is 30% or more then the referenced-scaled average bioequivalence approach will be used. All plasma samples will be assayed for asenapine using a fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 289727 0
0, 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 32, 48, 56 and 72 hours
Secondary outcome [1] 303113 0
Time to maximum peak concentration (Tmax) and the elimination half life (t1/2). Tmax will be the time where the maximum concentration occurred in the sample points. T1/2 = 0.693/Kel where kel is the terminal elimination rate constant.
Timepoint [1] 303113 0
0, 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 32, 48, 56 and 72 hours

Eligibility
Key inclusion criteria
Healthy males and Females
Aged between 18 and 55
Non-smoker
BMI between 19 and 30
Normal, healthy individuals as determined by medical history, physical examination, ECG, bood 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
Concomitant drug therapy of any kind (excluding prescribed hormonal contraceptives
Histroy of abnormal heartbeats or frequent palpitations or who have a family history of long QTc syndrome
History of orthostatic hypotension, fainting or dizziness, epilepsy or seizures, diabetes or neuroleptic malignant syndrome
History of depression, or other mental illness and/or have received treatment with antipsychotic medication
Pregnant or breast-feeding
Sensitivity to asenapine, any antipsychotic medicines, with excipients of asenapine
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.

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 three-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
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] 5125 0
New Zealand
State/province [1] 5125 0
Otago

Funding & Sponsors
Funding source category [1] 287396 0
Commercial sector/Industry
Name [1] 287396 0
Alembic Pharmaceutical Limited
Address [1] 287396 0
Alembic Road
Vadodara - 390 003
Gujarat
India
Country [1] 287396 0
India
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
156 Frederick Street
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 286137 0
None
Name [1] 286137 0
Address [1] 286137 0
Country [1] 286137 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289373 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 289373 0
Ministry of Health
1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 289373 0
New Zealand
Date submitted for ethics approval [1] 289373 0
09/05/2013
Approval date [1] 289373 0
12/06/2013
Ethics approval number [1] 289373 0
13/CEN/63

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test (new) formulation of 10 mg asenapine sublingual tablet relative to that of the reference formulation (innovator brand of 10 mg asenapine sublingual tablet) following oral administration of a single dose of 10 mg in healthy male and female 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 40522 0
Dr Noelyn Hung
Address 40522 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 40522 0
New Zealand
Phone 40522 0
+6434779669
Fax 40522 0
Email 40522 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 40523 0
Mrs Linda Folland
Address 40523 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 40523 0
New Zealand
Phone 40523 0
+6434779669
Fax 40523 0
Email 40523 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 40524 0
Dr Cheung-Tak Hung
Address 40524 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 40524 0
New Zealand
Phone 40524 0
+6434779669
Fax 40524 0
Email 40524 0
tak.hung@zenithtechnology.co.nz