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Trial registered on ANZCTR


Registration number
ACTRN12615000143527
Ethics application status
Approved
Date submitted
10/02/2015
Date registered
16/02/2015
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 melatonin prolonged release tablet against the innovator melatonin prolonged release tablet conducted under fasting conditions and at steady state in healthy male and female volunteers
Scientific title
A multiple dose, randomized, blinded, bioequivalence study of a test formulation of melatonin prolonged release tablet in a 2 way crossover comparison against the innovator melatonin prolonged release tablet conducted under fasting conditions and at steady state in healthy male and female volunteers
Secondary ID [1] 286140 0
None
Universal Trial Number (UTN)
U1111-1163-4921
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bioequivalence study conducted in healthy volunteers comparing two formulations of melatonin 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, melatonin is a naturally occurring hormone produced by the pineal gland and is indicated as monotherapy for the short term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 or over.
294149 0
Condition category
Condition code
Other 294470 294470 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
Multiple dose, crossover over study design whereby each participant receives the test formulation of melatonin (1 x 2 mg) on five occasions and the innovator formulation of melatonin (1 x 2 mg) on five occasions with each dose seperated by a 10 day washout period.

Each dose (1 x 2 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.

Participants are required not to eat for 10 hours before receiving each dose.

On study days 1 to 4 and 15 to 18 subjects will report to Zenith Technology for dosing and the provision of one blood sample. They will then be given a light breakfast to consume following each dose at home.

On study day 5 and 19 no water is allowed for 1 hour prior to dosing until 1 hour after dosing (except for the water consumed with the dose) and 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 can be monitored and for 24 hours after dosing.

On study days 5 and 19 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 on study days 5 and 19.

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] 291142 0
Treatment: Drugs
Comparator / control treatment
Multiple dose, crossover study design whereby each participant receives the test formulation of melatonin (1 x 2 mg) on five occasions and the innovator formulation of melatonin (1 x 2 mg) on five occasions with each dose seperated by a 10 day washout period. The comparator/control for this trial is the innovator formulation of melatonin.
Control group
Active

Outcomes
Primary outcome [1] 294253 0
To compare the bioavailability of melatonin (as summarised by AUC0-t(ss), Cmax(ss) and Cmin(ss)) for the two formulations. All plasma samples will be assayed for melatonin using a fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 294253 0
Pre-dose samples on study days 1 to 4 and 15 and 18 and -1.0,-0.5, 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 16, 18, 20 and 24 hours on study days 5 and 19
Secondary outcome [1] 312880 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] 312880 0
Pre-dose samples on study days 1 to 4 and 15 and 18 and -1.0,-0.5, 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 16, 18, 20 and 24 hours on study days 5 and 19

Eligibility
Key inclusion criteria
Healthy male and non-pregnant females
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
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
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 melatonin or any other similar class of medicines, or the excipients of melatonin
History of any conditions that might interfere with the absorption, distribution, metabolism or excretion of the drug
Females who are pregnant and/or are breastfeeding
Who are planning to start a family within 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
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] 6644 0
New Zealand
State/province [1] 6644 0
Otago

Funding & Sponsors
Funding source category [1] 290714 0
Commercial sector/Industry
Name [1] 290714 0
Generic Partners Pty Ltd
Address [1] 290714 0
Suite 3, 191 Riversdale Road
Hawthorn
VIC 3122
Country [1] 290714 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] 289403 0
None
Name [1] 289403 0
Address [1] 289403 0
Country [1] 289403 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292345 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 292345 0
Ministry of Health
1 the Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 292345 0
New Zealand
Date submitted for ethics approval [1] 292345 0
Approval date [1] 292345 0
06/12/2014
Ethics approval number [1] 292345 0
14/NTA/192

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test (new) formulation of 2 mg melatonin tablet relative to that of the reference formulation (innovator brand of 2 mg melatonin tablet) following oral administration of a multiple dose of 2 mg in healthy male and female subjects under fasting conditions and at steady state.
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 54798 0
Dr Noelyn Hung
Address 54798 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 54798 0
New Zealand
Phone 54798 0
+6434779669
Fax 54798 0
+6434779605
Email 54798 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 54799 0
Mrs Linda Folland
Address 54799 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 54799 0
New Zealand
Phone 54799 0
+6434779669
Fax 54799 0
+6434779605
Email 54799 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 54800 0
Dr Cheung-Tak Hung
Address 54800 0
Zenith Technology Corporation Limited 156 Frederick Street (PO Box 1777) Dunedin 9016
Country 54800 0
New Zealand
Phone 54800 0
+6434779669
Fax 54800 0
+6434779605
Email 54800 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