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Trial registered on ANZCTR


Registration number
ACTRN12619001017112
Ethics application status
Approved
Date submitted
4/07/2019
Date registered
16/07/2019
Date last updated
2/07/2021
Date data sharing statement initially provided
16/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparative assessment of the absorption of a generic formulation of paracetamol / ibuprofen / doxylamine tablet against the innovator paracetamol / codeine phosphate hemihydrate / doxylamine succinate tablets and paracetamol / ibuprofen tablet conducted under fasting conditions in healthy male and female volunteers
Scientific title
A single dose, blinded, balanced, randomised, three-treatment, three period, six sequence, three-way crossover bioequivalence study comparing an immediate release tablet containing 500 mg paracetamol / 200 mg ibuprofen / 5.1 mg doxylamine with Dolased® immediate release tablets containing 500 mg paracetamol / 10 mg codeine phosphate hemihydrate / 5.1 mg doxylamine succinate and Nuromol® immediate release tablets containing 500 mg paracetamol / 200 mg ibuprofen in healthy male and female subjects under fasting conditions.
Secondary ID [1] 298624 0
Nil
Universal Trial Number (UTN)
U1111-1230-8533
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain


 313486 0
Fever 313650 0
Inflammation 313651 0
Allergy 313652 0
Condition category
Condition code
Inflammatory and Immune System 311912 311912 0 0
Other inflammatory or immune system disorders
Anaesthesiology 312027 312027 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single dose, three-treatment, three-period, six-sequence, crossover, bioequivalence design whereby each participant receives the test formulation of 1 x 500 mg paracetamol, 200 mg ibuprofen and 5.1 mg doxylamine succinate immediate release tablet on one occasion and the innovator formulations of 1 x 500 mg paracetamol, 10 mg codeine phosphate hemihydrate and 5.1 mg doxylamine succinate immediate release tablet on one occasion and 1 x 500 mg paracetamol and 200 mg ibuprofen immediate release tablet on one occasion with each dose seperated by a one week washout period. The intervention for this trial is the test formulation of 500 mg paracetamol, 200 mg ibuprofen and 5.1 mg doxylamine succinate.

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] 314883 0
Treatment: Drugs
Comparator / control treatment
Single dose, three treatment, three period, six sequence, crossover study design whereby each participant receives the test formulation of paracetamol, 200 mg ibuprofen and 5.1 mg doxylamine succinate on one occasion and the innovator formulation of 500 mg paracetamol, 10 mg codeine phosphate hemihydrate and 5.1 mg doxylamine succinate on one occasion and 500 mg paracetamol and 200 mg ibuprofen on one occassion with each dose separated by a one week washout period. The comparator/control for this trial is the innovator formulation of paracetamol, 200 mg ibuprofen and 5.1 mg doxylamine succinate .
Control group
Active

Outcomes
Primary outcome [1] 320581 0
This is a composite primary outcome to compare the bioavailability of paracetamol, ibuprofen and doxylamine (as summarised by Cmax and AUC) for all formulations. All plasma samples will be assayed for paracetamol, ibuprofen and doxylamine using one fully validated LC/MS/MS method. Validation will be conducted to comply with EU and FDA guidelines. Codeine phosphate will not be analysed in this study.
Timepoint [1] 320581 0
Prior to dosing and at 10 min, 20 min, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 16, 20, 24, 36 and 48 hours post dosing.
Secondary outcome [1] 372102 0
This is a composite secondary outcome measuring Time to maximum peak concentration (Tmax) for paracetamol, ibuprofen and doxylamine combined in one assay. Tmax will be the time where the maximum concentration occurred in the sample points.
Timepoint [1] 372102 0
Prior to dosing and at 10 min, 20 min, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 14, 16, 20, 24, 36 and 48 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
Sex
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 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, B and C. 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 three-way partial replicate 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
19/07/2019
Actual
19/07/2019
Date of last participant enrolment
Anticipated
Actual
5/08/2019
Date of last data collection
Anticipated
Actual
5/08/2019
Sample size
Target
24
Accrual to date
Final
24
Recruitment outside Australia
Country [1] 21650 0
New Zealand
State/province [1] 21650 0
Otago

Funding & Sponsors
Funding source category [1] 303164 0
Commercial sector/Industry
Name [1] 303164 0
Soul Pattinson (Manufacturing) Pty Ltd
Country [1] 303164 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] 303167 0
None
Name [1] 303167 0
Address [1] 303167 0
Country [1] 303167 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303726 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 303726 0
Ministry of Health
Freyberg Building
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 303726 0
New Zealand
Date submitted for ethics approval [1] 303726 0
09/04/2019
Approval date [1] 303726 0
07/05/2019
Ethics approval number [1] 303726 0
19/CEN/66

Summary
Brief summary
The objective of this study is to evaluate the bioequivalence by comparing the rate and extent of absorption of the test formulation, a 500 mg paracetamol / 200 mg ibuprofen / 5.1 mg doxylamine succinate immediate release tablet relative to that of the reference formulations, an immediate release tablet containing 500 mg paracetamol / 10 mg codeine phosphate hemihydrate / 5.1 mg doxylamine succinate and an immediate release tablet containing 500 mg paracetamol / 200 mg ibuprofen 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 94586 0
Dr Noelyn Hung
Address 94586 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 94586 0
New Zealand
Phone 94586 0
+64 3 477 9669
Fax 94586 0
+6434779605
Email 94586 0
[email protected]
Contact person for public queries
Name 94587 0
Linda Folland
Address 94587 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 94587 0
New Zealand
Phone 94587 0
+64 3 477 9669
Fax 94587 0
+6434779605
Email 94587 0
[email protected]
Contact person for scientific queries
Name 94588 0
Cheung Tak Hung
Address 94588 0
Zenith Technology Corporation Limited
156 Frederick Street (PO Box 1777)
Dunedin 9016
Country 94588 0
New Zealand
Phone 94588 0
+64 3 477 9669
Fax 94588 0
+6434779605
Email 94588 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.