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Trial registered on ANZCTR


Registration number
ACTRN12616000419460
Ethics application status
Approved
Date submitted
30/03/2016
Date registered
1/04/2016
Date last updated
20/12/2018
Date data sharing statement initially provided
20/12/2018
Date results information initially provided
20/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pharmacokinetic study of four orally formulated combinations of acetaminophen and ibuprofen in healthy volunteers under fed conditions
Scientific title
A single dose, four-way, open-label study to determine the pharmacokinetics and bioavailability of an oral suspension of combined acetaminophen and ibuprofen, a powder sachet of combined acetaminophen and ibuprofen for oral solution and two tablet formulations of combined acetaminophen and ibuprofen in 28 healthy volunteers under fed conditions.
Secondary ID [1] 288879 0
AFT-MX-14B
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pain relief 298178 0
Condition category
Condition code
Anaesthesiology 298338 298338 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Each participant will be randomly allocated to receive a single dose of each of the following treatments in a four-way cross-over sequence:
- Treatment A: oral suspension containing 1000 mg acetaminophen + 300 mg ibuprofen in 31.25 mL
- Treatment B: powder sachet containing 1000 mg acetaminophen + 300 mg ibuprofen for oral solution
- Treatment C: tablets providing total dose of 1000 mg acetaminophen + 300 mg ibuprofen
- Treatment D: tablets providing total dose of 975 mg acetaminophen + 292.5 mg ibuprofen

The administration of doses will be supervised on site.
All treatments will be administered under fed conditions. Participants will be fasted for at least 10 hours overnight and receive a standardized breakfast served 30 minutes prior to study drug administration. This breakfast will supply around 967 kcal about 50% of which are fat calories. A standardized meal will be served approximately 5 hours after dosing and a snack will be provided approximately 9 hours after study drug administration. Water will be restricted for 1 hour pre-dose and 1 hour post-dose (with the exception of water administered as part of dosing).

Administration
- Oral Suspension formulation: 31.25 mL of the oral suspension will be dispensed for consumption. Any residue remaining after initial administration will be resuspended with 240 mL of water and consumed.
- Powder Sachet formulation: contents of the sachet will be dissolved in 240 mL hot water and consumed once cold.
- Tablet Formulations: will be administered with 240 mL of water.

Dose-frequency is single doses of four different formulations separated by a washout period of 3 days.
All participants will complete the four periods in cross-over fashion.
Intervention code [1] 294337 0
Treatment: Drugs
Comparator / control treatment
Treatment C: tablets providing total dose of 1000 mg acetaminophen + 300 mg ibuprofen
Control group
Active

Outcomes
Primary outcome [1] 297811 0
To determine the pharmacokinetic parameters (Cmax, AUC(0-t), AUC(0-inf), Tmax, Kel, t1/2) of acetaminophen and ibuprofen and compare between four treatment groups, under fed conditions.
Timepoint [1] 297811 0
Single-dose study measuring plasma concentration of acetaminophen and ibuprofen pre-dose and at 5, 15, 30, 45 minutes and 1.00, 1.25, 1.50, 2.00, 3.00, 6.00, 8.00, 10.00 and 12.00 hours after study drug administration.
Secondary outcome [1] 322303 0
An acute safety evaluation will be performed during each study period by recording spontaneously reported adverse events and by clinical assessments.
Known NSAID adverse effects (i.e. GI ulceration, indigestion/stomach pain, GI bleeding, bronchospasm, water retention, renal failure, skin reactions and thromboembolic events), and known adverse effects of acetaminophen (i.e. clinical evidence of hepatotoxicity) will be compared between groups.
Adverse events will continue to be assessed up to 7 days after the last dose of the study medication by spontaneous reporting and at a final follow-up phone call.
Timepoint [1] 322303 0
Safety will be evaluated during each study period (from administration to 12 hours post administration for each formulation), and for 7 days following study drug administration.

Eligibility
Key inclusion criteria
Healthy subjects, males and females aged 18 to 50 years of age.
Females must be sterile or using adequate contraception.
Participants must not have taken any prescription medications for at least 14 days or over-the-counter medications for at least 3 days before the start of each study phase, with the exception of oral contraceptives and the study medication.
All subjects must be deemed healthy on the basis of a medical history, physical exam (including vital signs and 12-lead ECG recording), urinalysis, and blood biochemical, haematological and serological examinations.
Minimum age
18 Years
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women who are pregnant, nursing, unwilling to take adequate contraceptive precautions or undergo a urine pregnancy test
Excess weekly alcohol consumption
History of drug abuse
Smoking > 10 cigarettes per day
Unwilling to abstain from smoking throughout duration of the study
Unable to abstain from prescription drugs within 14 days prior to the study, vitamins within 2 days prior to the study, grapefruit containing foods or beverages within 7 days prior to the study or caffeine containing foods or beverages within 24 hours prior to the study
Used OTC herbal products within 3 days prior to the study
Participating in another clinical trial within 80 days
Clinically significant abnormal laboratory tests.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Pharmacokinetics
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] 7755 0
Jordan
State/province [1] 7755 0
Amman

Funding & Sponsors
Funding source category [1] 293228 0
Commercial sector/Industry
Name [1] 293228 0
AFT Pharmaceuticals Ltd
Address [1] 293228 0
Level 1, 129 Hurstmere Rd
Takapuna
Auckland, 0622
New Zealand
Country [1] 293228 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
AFT Pharmaceuticals Ltd
Address
Level 1, 129 Hurstmere Rd
Takapuna
Auckland, 0622
New Zealand
Country
New Zealand
Secondary sponsor category [1] 292029 0
None
Name [1] 292029 0
Address [1] 292029 0
Country [1] 292029 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294707 0
International Pharmaceutical Research Centre (IPRC)
Ethics committee address [1] 294707 0
1 Queen Rania Street
Sport City Circle
Amman 11196
Jordan
Ethics committee country [1] 294707 0
Jordan
Date submitted for ethics approval [1] 294707 0
01/04/2016
Approval date [1] 294707 0
05/04/2016
Ethics approval number [1] 294707 0

Summary
Brief summary
The study is designed as a Phase 1 trial to evaluate and compare the pharmacokinetic profile of four orally formulated combinations of acetaminophen and ibuprofen administered in cross-over fashion to 28 healthy volunteers under fed conditions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 64774 0
Dr Majdi Abu Awida
Address 64774 0
International Pharmaceutical Research Centre (IPRC)
1 Queen Rania Street
Sport City Circle
Amman 11196
Jordan
Country 64774 0
Jordan
Phone 64774 0
+962-6-5627648
Fax 64774 0
Email 64774 0
iprc@iprc.com.jo
Contact person for public queries
Name 64775 0
Dr Hartley Atkinson
Address 64775 0
AFT Pharmaceuticals Ltd
Level 1, 129 Hurstmere Rd
Takapuna
Auckland, 0622
New Zealand
Country 64775 0
New Zealand
Phone 64775 0
+6494880232
Fax 64775 0
Email 64775 0
hartley@aftpharm.com
Contact person for scientific queries
Name 64776 0
Dr Hartley Atkinson
Address 64776 0
AFT Pharmaceuticals Ltd
Level 1, 129 Hurstmere Rd
Takapuna
Auckland, 0622
New Zealand
Country 64776 0
New Zealand
Phone 64776 0
+6494880232
Fax 64776 0
Email 64776 0
hartley@aftpharm.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 871 0
Aitken P, Salem II, Stanescu I, Playne R, Atkinson HC (2018) A Single Dose, Four-Way, Open-Label Bioavailability Study of Oral
Acetaminophen and Ibuprofen Combinations (Maxigesic®) under both Fasting and Fed Conditions. J Bioequiv Availab 10: 84-91. 383. doi:
10.4172/0975-0851.1000383
Attachments [1] 871 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary
The study confirmed that the maximum blood level and the time profile of the drugs in the body of four different formulations (oral suspension, oral sachet, oral tablet of acetaminophen 500mg + ibuprofen 150mg and oral tablet of acetaminophen 325mg + ibuprofen 97.5mg) of a fixed dose combination containing acetaminophen and ibuprofen are all similar in healthy adults under fed conditions.
All these four different formulations are well tolerated.