A Comparative Bioavailability Study of Reformulated Ibuprofen 2% and 4% Oral Suspensions (Berlin Chemie AG) and Versus Ibuprofen (Nurofen®) 200 mg/5 ml Oral Suspension

Exclusion Criteria

• •1. History or presence of allergies.
• •2. Known hypersensitivity or intolerance to ibuprofen or other non-steroidal anti-inflammatory drugs (NSAIDs), fructose and/or any excipient of the IMP.
• •3. History of bronchospasm, asthma, rhinitis, angioedema or urticaria associated with the intake of acetylsalicylic acid or other NSAIDs.
• •4. History or presence of significant cardiovascular (including congestive heart failure (NYHA IV), arterial hypertension, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease), pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, infectious, dermatologic, neurologic, or psychiatric disease.
• •5. History of recurrent peptic ulcer or gastrointestinal bleeding (\>2 distinct episodes of proven ulceration or bleeding) or history of gastrointestinal bleeding or perforation related to previous NSAID therapy.
• •6. Cerebrovascular or other active bleeding.
• •7. Acute infectious diseases of any organ system (including e.g., influenza, COVID-19, acute respiratory viral infections) less than 4 weeks before the first IMP dose.
• •8. History or presence of any other clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• •9. History of major abdominal surgery or minor abdominal surgery within 3 months before the first IMP dose.
• •10. Clinically significant deviations from the normal parameters (see study protocol Appendix 2 for guidance) in clinical blood count analysis, biochemical blood analysis, urinalysis.
• •11. Systolic blood pressure measured in a supine position \< 100 mmHg or \> 130 mmHg and/or diastolic blood pressure \< 60 mmHg or \> 89 mmHg.
• •12. Heart rate \< 60 or \> 100 beats per minute.
• •13. Female subjects who were attempting to conceive, pregnant or lactating.
• •14. Positive test results for HIV or hepatitis B (HBsAg, anti-HBc) or hepatitis C (anti-HCV) or syphilis at screening.
• •15. Positive screen for drugs of abuse or alcohol at screening.
• •16. Positive test result for cotinine in urine at screening.
• •17. Known or suspected drug or alcohol abuse as judged by the Investigator.
• •18. Alcohol consumption more than 10 units of alcohol a week (1 unit = 200 mL of dry wine or 50 mL of strong alcoholic drinks or 500 mL of beer) within 6 months before the first IMP dose.
• •19. Intake of methylxanthine containing substances (e.g., coffee, tea, chocolate, cocoa, energy drinks, cola) as well as citrus fruits and cranberry (including juices, fruit drinks, etc.) within the last 24 h before the first IMP dose.
• •20. Intake of medications that had a significant effect on circulatory dynamics, liver function, etc. (barbiturates, omeprazole, cimetidine, NSAIDs, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, diuretics, etc.) within the 2 months before the first IMP dose.
• •21. Use of any prescribed or nonprescribed medication, herbal remedies, vitamins and minerals within the 2 weeks before the first IMP dose or longer (at least 5 elimination half-lives) if the medication has a long half-life.
• •22. Mental, physical and other reasons that did not allow the subjects according to Investigator's opinion to assess their behavior adequately, to follow correctly the requirements of the clinical study protocol and to assess the expected risks and possible discomfort.
• •23. Dehydration (e.g. due to diarrhea, vomiting, or other causes) within the last 48 h before the first IMP dose.
• •24. Subjects who had been on a special diet (for whatever reason, e.g., vegetarians or hypocaloric diet \[\< 1000 kcal/day\]) within the 28 days before the first IMP dose.
• •25. Plasma donation within 1 month of screening or blood donation/blood loss \>500 mL within the 3 months before screening.
• •26. Unwillingness or inability to follow the procedures and restrictions outlined in the protocol and the ICF.
• •27. Participation in another clinical study within the 3 months before the first IMP dose in this study.
• •28. Female subjects with childbearing potential, having unprotected sexual intercourse with any unsterilized male partner (i.e., a man who is not sterilized by vasectomy for at least 6 months) within the 30 days before the first IMP dose.
• •29. Any reason in the opinion of the Investigator, would prevent the subject from participating in the study.