Clinical trial NCT03180879: Ibuprofen Bioavailability Study
Official title: An Open Label, Randomised, Single Dose, Three-way Crossover Study to Compare the Bioavailability of 400 mg Ibuprofen From 2 x 200 mg Ibuprofen Acid Orodispersable Tablets, 2x 200 mg Ibuprofen Acid Tablets and 2 x 342 mg Ibuprofen Lysine Tablets in Fasted Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Reckitt Benckiser Healthcare (UK) Limited
Sponsor class: INDUSTRY
Collaborators: name: Simbec Research
First posted: 2017-06-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: This project is the in-house development of a 200 mg ibuprofen acid orodispersable tablet (ODT; meltlet). It is designed to appeal to consumers who want a dosage form that may be taken without water and can be used 'on the go'. Vanquish has an improved organoleptic profile compared to the currently marketed meltet by the Sponsor. ODTs are also considered as a suitable dosage form for children who may be reluctant to swallow tablets. This product has the potential for application in both adults and children due to the convenience of the format and the ease of administration for both groups.

This will be the first pharmacokinetic (PK) assessment of the ibuprofen acid ODT formulation.


Eligibility criteria: Inclusion Criteria:

1. Male or female subjects who have given written informed consent.
2. Age: ≥ 18 years ≤ 50 years.
3. Body Mass Index (BMI) of ≥ 18.0 and ≤ 30 kg/m2.
4. Healthy as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening.
5. Female subject of child bearing potential with a negative pregnancy test at the screening visit and willing to use an effective method of contraception unless of non-childbearing potential or where abstaining from sexual intercourse in line with the preferred and usual lifestyle of the subject from first dose until 3 months after the final dose of study medication.
6. Female subject of non-child bearing potential with negative pregnancy test at the screening visit.
7. Male subject willing to use an effective method of contraception unless anatomically sterile or where abstaining from sexual intercourse in line with the preferred and usual lifestyle of the subject from first dose until 3 months after the final dose of study medication.

Exclusion Criteria:

1. Pregnant or lactating females.
2. A history and/or presence of significant disease of any body system, including significant psychiatric disorders, parasuicide.
3. Any condition that may currently interfere with the absorption, distribution, metabolism or excretion of drugs.
4. A history of allergy or intolerance related to treatment with ibuprofen, aspirin or other non-steriodal anti-inflammatory drugs (NSAIDs), or the excipients of the formulations
5. A history of or active peptic or duodenal ulcers or gastrointestinal 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 significant and frequent migraine.
8. Current smokers or ex-smokers who have smoked or used nicotine replacement products during the 6 months prior to the first dose of study medication.
9. A history of substance abuse (including alcohol).
10. Consumption of foods or beverages containing caffeine (e.g. coffee, tea, cola and chocolate) above 300 mg caffeine per day, prior to 48 hours of each treatment period. (One cup of coffee equals approximately 50 mg caffeine).
11. Those with positive test for drugs of abuse and alcohol.
12. Ingestion of a prescribed drug at any time in the 14 days before the first dose of study medication (excluding hormonal contraceptives and hormone replacement therapy), or consumption of enzyme inhibitors or inducers 30 days prior to the first dose of study medication (such as barbiturates, carbamazepine, erythromycin, phenytoin, etc.).
13. Ingestion of an over-the-counter preparation within 7 days before the first dose of study medication, including herbal medications, vitamins, fish oil supplements, ibuprofen and other NSAIDs.
14. Those who have consumed grapefruit or grapefruit juice, pumelo or Seville oranges in the 7 days before the first dose of study medication.
15. Donation of blood \> 400 mL e.g. to the blood transfusion service in the 12 weeks prior to the first dose of study medication.
16. Known human immune deficiency virus (HIV) positive status, or a positive viral serology test.
17. Topical use of ibuprofen within 7 days before the first dose of study medication.
18. Strenuous physical exercise from 48 hours prior to first dose of study medication.
19. Those previously randomised into this study.
20. Those who are an employee at the study site.
21. Those who are a partner or first degree relative of the Investigator.
22. Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of study medication.
23. Those unable in the opinion of the Investigator to comply fully with the study requirements.

Primary outcomes:
measure: AUC0-t - the area under plasma concentration curve from administration to last quantifiable concentration at time t.
timeFrame: PK Analysis 0-12hrs
measure: Cmax - the maximum observed plasma concentration.
timeFrame: PK Analysis 0-12hrs
Secondary outcomes:
measure: AUC0-t - the area under plasma concentration curve from administration to last quantifiable concentration at time t.
timeFrame: PK Analysis 0-12hrs
measure: Cmax - the maximum observed plasma concentration.
timeFrame: PK Analysis 0-12hrs
measure: Kel - Elimination rate constant
timeFrame: PK Analysis 0-12hrs
measure: AUC0-inf - Area under the plasma concentration-time curve from administration to infinity
timeFrame: PK Analysis 0-12hrs
measure: AUCR - Ratio AUC0-t/AUC0-inf
timeFrame: PK Analysis 0-12hrs
measure: Tmax - Time until Cmax is first achieved
timeFrame: PK Analysis 0-12hrs
measure: T1/2 - Plasma concentration (elimination) half-life
timeFrame: PK Analysis 0-12hrs
measure: Cn - The plasma concentration at each planned nominal time point.
timeFrame: PK Analysis 0-12hrs
Other outcomes:
measure: Overall proportion of subjects with adverse events (AEs), i.e. the occurrence of one or more AEs per subject
timeFrame: Through study completion - Screening to study follow-up (approx 6 weeks)
measure: Change from baseline in oral temperature.
timeFrame: Through study completion - Screening to study follow-up (approx 6 weeks)
measure: Change from baseline in resting heart rate.
timeFrame: Through study completion - Screening to study follow-up (approx 6 weeks)
measure: Change from baseline in resting blood pressure..
timeFrame: Through study completion - Screening to study follow-up (approx 6 weeks)
measure: Change from baseline in standard haematology testing.
timeFrame: Through study completion - Screening to study follow-up (approx 6 weeks)
measure: Change from baseline in standard biochemistry testing.
timeFrame: Through study completion - Screening to study follow-up (approx 6 weeks)
measure: Change from baseline in standard urinary testing.
timeFrame: Through study completion - Screening to study follow-up (approx 6 weeks)
Locations:
city: Merthyr Tydfil
country: United Kingdom
facility: Simbec Research
Study officials:
affiliation: Simbec Research
name: Annelize Koch, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sugar D, Francombe D, da Silva T, Hanid S, Hutchings S. Comparative Bioavailability Study of a New Orodispersible Formulation of Ibuprofen Versus Two Existing Oral Tablet Formulations in Healthy Male and Female Volunteers. Clin Ther. 2019 Aug;41(8):1486-1498. doi: 10.1016/j.clinthera.2019.04.040. Epub 2019 Jun 12.