Clinical trial NCT02452450: Ibuprofen and Paracetamol Pharmacokinetic Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer Study
Lead sponsor: Reckitt Benckiser Healthcare (UK) Limited
Sponsor class: INDUSTRY
Collaborators: name: Simbec Research
First posted: 2015-05-22
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study was to determine rates of absorption of Ibuprofen and Paracetamol formulations.


Eligibility criteria: Inclusion Criteria:

1. Age: \> 18 to \< 50 years.
2. Sex: Male and female subjects are eligible for entry.
3. Female subject of child bearing potential with a negative pregnancy test at the screening visit and willing to use an effective method of contraception, if applicable
4. Female subject of non-child bearing potential with negative pregnancy test at the screening visit.
5. Male subject willing to use an effective method of contraception.
6. Status: Healthy volunteers with a body mass index of \>18 and \<30 kg/m2.
7. Absence of relevant abnormalities in the clinical examination, ECG, drug and safety analysis.
8. Subjects who have given written informed consent

Exclusion Criteria:

1. Pregnant or lactating female subjects.
2. A history of significant disease of any body-system.
3. Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs.
4. A history of allergy or intolerance (including angio-oedema, urticaria, bronchospasm and rhinitis) related to treatment with ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, or the excipients of the formulations.
5. A history of peptic or duodenal ulcers or gastro-intestinal bleed or upper gastro-intestinal bleed, or other significant gastro-intestinal disorders.
6. A history of frequent dyspepsia, e.g., heartburn or indigestion.
7. A history of migraine.
8. A history of psychotic illness, attempted suicide or parasuicide.
9. Current smokers and ex-smokers who have smoked within 6 months.
10. A history of drug abuse (including alcohol).
11. High consumption of stimulating drinks
12. Those with positive drugs of abuse screen including alcohol on any occasion throughout the study.
13. Ingestion of a prescribed drug at any time in the 14 days before dosing with study medication (excluding hormonal contraceptives and hormone replacement therapy), or consumption of enzyme inhibitors or inducers during the previous month (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc).
14. Ingestion of an over-the-counter preparation within 7 days before dosing with study medication, including herbal medications, vitamin/fish oil supplements, ibuprofen and other NSAIDs and paracetamol.
15. Donation of blood in quantity in the previous 12 weeks before enrolment into the study
16. Known human immune deficiency virus (HIV) positive status, or a positive viral serology screen.
17. Topical use of ibuprofen within 7 days before dosing with study medication
18. Those previously randomised into this study.
19. Employee at study site.
20. Partner or first degree relative of the investigator.
21. Those with an ibuprofen level \> 10 ng/ml as determined at pre-study screening visit 2 (Part 2 (Pivotal Phase) of the study only).
22. Those who are unwilling to consume gelatin of animal origin (Part 2 (Pivotal Phase) of the study only).
23. Those who have participated in a clinical trial in the previous 12 weeks
24. Those unable in the opinion of the Investigator to comply fully with the study requirements.

Primary outcomes:
measure: Time to the maximum concentration (Cmax) of the reference Ibuprofen
timeFrame: 0-4hr
measure: Time to the first extrapolated non-zero concentration (Tlag)
timeFrame: 0-4hr
measure: Time to the maximum concentration (Tmax)
timeFrame: 0-4hr
Secondary outcomes:
measure: Time to the lower therapeutic level reaching at least 5 µg/ml (T5.0) for ibuprofen and paracetamol
timeFrame: 0-4hr
measure: Time to the mid therapeutic level reaching at least 8.4 µg/ml (T8.4) for ibuprofen and 10 µg/ml (T10.0) for paracetamol
timeFrame: 0-4hr
measure: Time to the higher therapeutic level reaching at least 10.0 µg/ml (T10.0) for ibuprofen and 20 µg/ml (T20.0) for paracetamol
timeFrame: 0-4hr
measure: Partial area under the curve (AUCs) at each nominal blood sampling time-point
timeFrame: 0-4hr
measure: The area under the curve up to the median Tmax for the ibuprofen reference product (AUCTmaxRef)
timeFrame: 0-4hr
measure: The plasma concentration at each planned nominal time-point (Cn)
timeFrame: 0-4hr
measure: The maximum plasma concentration (Cmax)
timeFrame: 0-4hr
Other outcomes:
Locations:
Study officials:
References:
citation: Miles L, Hall J, Jenner B, Addis R, Hutchings S. Predicting rapid analgesic onset of ibuprofen salts compared with ibuprofen acid: Tlag, Tlow, Tmed, and a novel parameter, TCmaxRef. Curr Med Res Opin. 2018 Aug;34(8):1483-1490. doi: 10.1080/03007995.2018.1466697. Epub 2018 Apr 27.