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Trial registered on ANZCTR


Registration number
ACTRN12617000739314
Ethics application status
Approved
Date submitted
17/05/2017
Date registered
22/05/2017
Date last updated
22/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of paracetamol/codeine phosphate hemihydrate/doxylamine succinate tablet against the innovator paracetamol/codeine phosphate hemihydrate/doxylamine succinate tablet conducted under fasting conditions in healthy male and female volunteers
Scientific title
A single dose, randomized, blinded, bioequivalence study of a test formulation of paracetamol/codeine phosphate hemihydrate/doxylamine succinate combination tablet in a 2 way crossover comparison against the innovator paracetamol/codeine phosphate hemihydrate/doxylamine succinate tablet conducted under fasting conditions in healthy male and female volunteers
Secondary ID [1] 291944 0
Nil
Universal Trial Number (UTN)
U1111-1195-1813
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe pain.
303286 0
Condition category
Condition code
Anaesthesiology 302716 302716 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, crossover study design whereby each participant receives the test formulation of 450 mg paracetamol/30 mg codeine phosphate hemihydrate/5 mg doxylamine succinate tablet on one occasion and the innovator formulation of 450 mg paracetamol/30 mg codeine phosphate hemihydrate/5 mg doxylamine succinate tablet on one occasion with each dose seperated by a one week washout period. The intervention for this trial is the test tablet formulation.

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 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 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 health of participants along with HIV, Hepatitis and drugs of abuse testing.

Each dose (1 x 450/30/5 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] 298068 0
Treatment: Drugs
Comparator / control treatment
Single dose, crossover study design whereby each participant receives the test formulation of (1 x 450/30/5 mg) on one occasion and the innovator formulation of paracetamol/codeine phosphate hemihydrate/doxylamine succinate tablet (1 x 450/30/5 mg) on one occasion with each dose seperated by a one week washout period. The comparator/control for this trial is the innovator tablet formulation.
Control group
Active

Outcomes
Primary outcome [1] 302156 0
To compare the bioavailability of paracetamol/codeine/doxylamine (as summarised by Cmax and AUC) for the formulation. All plasma samples will be assayed for paracetamol, codeine and doxylamine using a fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines.
Timepoint [1] 302156 0
0, 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24 and 36 hours post dosing
Secondary outcome [1] 334987 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] 334987 0
0, 0.16, 0.33, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 14, 16, 20, 24 and 36 hours post dosing

Eligibility
Key inclusion criteria
Healthy male and non-pregnant females
Aged between 18 and 55
Non-smoker
BMI between 18.5 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
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
Sensitivity to the study drug
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
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.
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.
Sequence generation will be by using a simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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] 8909 0
New Zealand
State/province [1] 8909 0
Otago

Funding & Sponsors
Funding source category [1] 296456 0
Commercial sector/Industry
Name [1] 296456 0
Medreich Australia Pty Ltd
Address [1] 296456 0
Unit 8, Homebush Business Village
11-21 Underwood Road
Homebusy, NSW 2140
Country [1] 296456 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zenith Technology Corporation Limited
Address
156 Frederick Street
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 295412 0
None
Name [1] 295412 0
Address [1] 295412 0
Country [1] 295412 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297681 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 297681 0
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 297681 0
New Zealand
Date submitted for ethics approval [1] 297681 0
06/04/2017
Approval date [1] 297681 0
27/04/2017
Ethics approval number [1] 297681 0
17/NTA/66

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence of the test formulation relative to that of a reference formulation, following oral administration of a combination single dose of 450 mg paracetamol/30 mg codeine phosphate hemihydrate/5 mg doxylamine succinate to healthy male and female subjects under fasting conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74802 0
Dr Noelyn Hung
Address 74802 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 74802 0
New Zealand
Phone 74802 0
+6434779669
Fax 74802 0
+6434779605
Email 74802 0
noelyn.hung@otago.ac.nz
Contact person for public queries
Name 74803 0
Mrs Linda Folland
Address 74803 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 74803 0
New Zealand
Phone 74803 0
+6434779669
Fax 74803 0
+6434779605
Email 74803 0
linda.folland@zenithtechnology.co.nz
Contact person for scientific queries
Name 74804 0
Dr Cheung-Tak Hung
Address 74804 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 74804 0
New Zealand
Phone 74804 0
+6434779669
Fax 74804 0
+6434779605
Email 74804 0
tak.hung@zenithtechnology.co.nz

No data has been provided for results reporting
Summary results
Not applicable