Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000498796
Ethics application status
Approved
Date submitted
1/05/2013
Date registered
6/05/2013
Date last updated
23/05/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Impact of thickening agent on the absorption pharmacokinetics of crushed paracetamol tablets in a healthy population.
Scientific title
Randomised single dose open label study to determine the bioavailability of paracetamol when mixed with different types of food after an oral administration of two tablets to healthy adults under fasting conditions
Secondary ID [1] 282430 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bio-availability of paracetamol in healthy volunteers 289038 0
Condition category
Condition code
Other 289378 289378 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
This is a randomized study, on arrival at the venue participants (20 healthy volunteers) will receive a standard dose of 1 g paracetamol (two 500 mg tablets), and will receive one of the following treatments.

Treatment 1: Tablets will be swallowed whole with 250 ml of water.
Treatment 2: Tablets will be swallowed whole with 250 ml of water.
Treatment 3: Tablets that have been crushed and mixed with 100 ml of water will be swallowed, followed by another 150 ml water to be used to rinse the mouth during swallowing.
Treatment 4: Tablets that have been crushed and mixed with a commercial thickened fluid (15 g EasyThick) will be swallowed, followed by 250 ml water to be used to rinse the mouth during swallowing.
Treatment 5: Tablets that have been crushed and mixed with jam (15 g) will be swallowed, followed by 250 ml of water to be used to rinse the mouth during swallowing.
Washout period : 7 days
Intervention code [1] 287075 0
Treatment: Drugs
Comparator / control treatment
Paracetamol 1000mg
Frequency - single dose
Duration - single dose
Mode administration - oral tablet
There is two active control arm in the study. The treatment 1 and 2 in this arm is whole paracetamol and is orally administered.

There are three comparator arms in the study (treatments 3,4, and 5) investigating the effect of crush tablets mixed with water, jam, and commercially thickening agent (Easythick) on drug absorption when administered orally.

Subjects will receive each of the 5 treatments in a random order.

Easy Thick Ingredients: Maltodextrin, xanthum gum, vitamin C, calcium chloride.
Control group
Active

Outcomes
Primary outcome [1] 289482 0
This study will investigate the effect of a commercially available thickening agent (EasyThick) on drug absorption from crushed commercially available paracetamol tablets using saliva. This will be compared with other treatment options i.e., the use of whole tablets, crushed tablets mixed with water, and crushed tablets mixed with an alternative semi solid (jam).
Timepoint [1] 289482 0
Single dose study measuring salivary concentrations at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 40 min, 50 min, 1 hour, 1 hour 20 min, 1 hour 40 min, 2, 3, 4, 6, 7and 8 hours after study drug administration.
Secondary outcome [1] 302583 0
Intraindividual variability of paracetamol absorption from a whole tablet will be estimated using saliva samples.
Timepoint [1] 302583 0
Single dose study measuring salivary concentrations at 0 min, 5 min, 10 min, 15 min, 20 min, 30 min, 40 min, 50 min, 1 hour, 1 hour 20 min, 1 hour 40 min, 2, 3, 4, 6, 7and 8 hours after study drug administration

Eligibility
Key inclusion criteria
Male or Female
Age 18 to 65 years
Participant has had previous exposure to paracetamol with no adverse events.
Participants understand and voluntarily agree to participate in this study by providing written consent.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Previous history of allergy or sensitivity to paracetamol
Consumed paracetamol in the last 24 hours before the study
People for whom paracetamol treatment is contraindicated or for whom paracetamol safety and disposition could be altered (e.g. hepatic dysfunction)
Smokers
Pregnancy
Consumed food within 2 hour prior to the start of the study

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
In order to address the primary aims of the study, a sample size of 20 participants has been selected. Previous research has indicated that the between-subject variability in the extent and rate of absorption of paracetamol in healthy participants is within 15% ; therefore, in order to detect a 10% difference in pharmacokinetic parameters between the treatment groups, at 80% power and an a-level of 0.05, a sample size of 18 participants is considered sufficient. An extra 2 participants will be recruited to allow for a predicted 10% withdrawal rate. .

Paracetamol plasma concentration time profiles will be used for calculating absorption pharmacokinetics. Pharmacokinetic parameters will be estimated using concentration–time profile, and a standard model-independent approach will be used. Pharmacokinetic parameters also include: area under the concentration–time profile, maximum observed concentration, apparent volume of distribution.
To investigate the effect of thickening agents on paracetamol absorption, between group statistical comparisons of pharmacokinetic data will be performed using an analysis of variance (ANOVA). ANOVA will be used to assess the effect of treatment, sequence, period and subject nested in sequence, on natural log–transformed data of AUC, Cmax, and rate of absorption. The residual error (error mean square) will be used to construct the 90% confidence intervals for the ratio of treatment means. Pharmacokinetic and statistical analysis will be conducted using validated software. Treatment differences will be determined by P values and the significance will be set at a a-level of 0.05 for all statistical analyses.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
6/05/2013
Actual
3/05/2013
Date of last participant enrolment
Anticipated
30/09/2013
Actual
16/01/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 6812 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 287200 0
University
Name [1] 287200 0
The University of Queensland
Country [1] 287200 0
Australia
Primary sponsor type
Individual
Name
A/Prof Kathryn Steadman
Address
The University of Queensland
PACE, School of Pharmacy, 20 Cornwall Street, Woolloongabba, Queensland, 4102
Country
Australia
Secondary sponsor category [1] 285963 0
None
Name [1] 285963 0
Address [1] 285963 0
Country [1] 285963 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289193 0
The University of Queensland, Medical Research Ethics Committee (MREC), Behavioural & Social Sciences Ethical Review Committee (BSSERC).
Ethics committee address [1] 289193 0
Ethics committee country [1] 289193 0
Australia
Date submitted for ethics approval [1] 289193 0
23/11/2012
Approval date [1] 289193 0
12/12/2012
Ethics approval number [1] 289193 0
2012001319

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39726 0
Mr Chandramouli Radhakrishnan
Address 39726 0
The University of Queensland, PACE, School of Pharmacy
20 Cornwall Street, Woolloongabba, Qld 4102
Country 39726 0
Australia
Phone 39726 0
+ 61 7 3346 1996
Fax 39726 0
Email 39726 0
[email protected]
Contact person for public queries
Name 39727 0
Kathryn Steadman
Address 39727 0
The University of Queensland, PACE, School of Pharmacy
20 Cornwall Street, Woolloongabba, Qld 4102
Country 39727 0
Australia
Phone 39727 0
+61733461886
Fax 39727 0
Email 39727 0
[email protected]
Contact person for scientific queries
Name 39728 0
Kathryn Steadman
Address 39728 0
The University of Queensland, PACE, School of Pharmacy
20 Cornwall Street, Woolloongabba, Qld 4102
Country 39728 0
Australia
Phone 39728 0
+61733461886
Fax 39728 0
Email 39728 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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