Ibuprofen 4% (w/v) Pivotal Bioequivalence Study
Condition: Bioequivalence of the Test Formulation
Intervention: Nurofen for Children®; Algifor® Junior
Intervention description: Nurofen for Children® 400 mg/10 ml; Algifor® Junior 400 mg/20 ml
Intervention MeSH terms: Ibuprofen
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

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.