Clinical trial NCT03496324: Ibuprofen 4% (w/v) Pivotal Bioequivalence Study
Official title: A Randomised, Single-dose, 4-way Crossover, Open-label, Pharmacokinetic Study Comparing a 4% (w/v) Suspension of Ibuprofen With a Reference 2% (w/v) Suspension of Ibuprofen in the Fed and Fasted States.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioequivalence of the Test Formulation
Lead sponsor: Reckitt Benckiser Healthcare (UK) Limited
Sponsor class: INDUSTRY
First posted: 2018-04-12
Enrollment: 24
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: Bioequivalence evaluation of Nurofen for Children® with reference formulation of Algifor® Junior by determining and comparing the rate and extent of absorption in both fed and fasted states


Eligibility criteria: Inclusion Criteria:

1. Subjects who had given written informed consent.
2. Age: ≥18 years ≤50 years.
3. Sex: Male or female subjects who were eligible for entry.
4. Female subject of childbearing potential with a negative pregnancy test at the screening visit and who were willing to use an effective method of contraception, if applicable (unless of non-childbearing potential or where abstaining from sexual intercourse was in line with the preferred and usual lifestyle of the subject) from first dose until 3 months after the final dose of Investigational Medicinal Product (IMP). Effective forms of contraception included: established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate).
5. Female subject of non-child bearing potential with negative pregnancy test at the screening visit. For the purposes of this study, this was defined as the subject being amenorrheic for at least 12 consecutive months or at least 4 months post-surgical sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy with or without hysterectomy). Menopausal status was confirmed by demonstrating at screening that levels of follicle stimulating hormone (FSH) fell within the respective pathology reference range. In the event a subject's menopause status had been clearly established (for example, the subject indicated she had been amenorrheic for 10 years), but FSH levels were not consistent with a post-menopausal condition, determination of subject eligibility was at the discretion of the Principal Investigator following consultation with the Sponsor's Responsible Physician.
6. Male subject willing to use an effective method of contraception, if applicable (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 IMP.
7. Healthy subjects as determined by past medical history, physical examination, vital signs, electrocardiogram (ECG), and laboratory tests at screening.
8. Healthy subjects with a body mass index (BMI) of ≥20 and ≤27 kg/m2.

Exclusion Criteria:

1. Pregnant or lactating females.
2. A history and/or presence of significant disease of any body system, including psychiatric disorders as specified in Chapter 5 of the International Classification of Diseases (ICD) 10.
3. Any condition that may have interfered with the absorption, distribution, metabolism or excretion of drugs.
4. A history of allergy or intolerance (including angioedema, urticaria, bronchospasm and rhinitis) related to treatment with ibuprofen, aspirin or other non-steroidal 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 migraine.
8. Users of nicotine products i.e. current smokers and ex-smokers who had smoked within the 6 months prior to dosing with the study medication or users of cigarette replacements (e.g. e-cigarettes, nicotine patches or gums).
9. A history of substance abuse (including alcohol).
10. High consumption of stimulating drinks (coffee, tea, cola, energy drinks etc. total caffeine intake per day above 300 mg (1 cup of coffee equated to 50 mg)).
11. Those with positive screen/test for drugs of abuse including alcohol on any occasion throughout the study.
12. 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.).
13. 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 NSAID.
14. Donation of blood in quantity \>400 mL, e.g., to the blood transfusion service in the previous 12 weeks before enrolment into the study.
15. Known human immune deficiency virus (HIV) positive status, or a positive viral serology screen.
16. Topical use of ibuprofen within 7 days before dosing with IMP.
17. Those previously randomized into this study.
18. Employee at study site.
19. Partner or first degree relative of the Investigator.
20. Those who have participated in a clinical trial in the previous 12 weeks.
21. Those unable, in the opinion of the Investigator, to comply fully with the study requirements.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Ibuprofen
timeFrame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
measure: Area Under Plasma Concentration-time Curve From Administration to the Last Quantifiable Concentration at Time t (AUC0-t) of Ibuprofen
timeFrame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
Secondary outcomes:
measure: Elimination Rate Constant (Kel) of Ibuprofen
timeFrame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
measure: Area Under Plasma Concentration-time Curve From Administration to Infinity (AUC0-inf) of Ibuprofen
timeFrame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
measure: Ratio of AUC0-t/AUC0-inf (AUCR)
timeFrame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
measure: Time to Maximum Plasma Concentration (Tmax) of Ibuprofen
timeFrame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
measure: Plasma Concentration Half-life (T1/2) of Ibuprofen
timeFrame: Pre-dose (Day -1), 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 105, 120, 180, 240, 360, 480 and 720 minutes (Day 0) post-dose
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 7 (follow-up)
Other outcomes:
Locations:
Study officials:
References: