Bioequivalence
Conditions
Keywords
Bioequivalence, Healthy, Bioavailability, Ibuprofen
Brief summary
The present study will be conducted in order to assess bioequivalence of the Test product (Ibuprofen 400 mg oral powder) and the Reference product 1 (Brufen 400 mg film-coated tablet), an approved market product in the European Union. Testing for bioequivalence will be performed considering AUC0-tlast and Cmax obtained after oral single dose fasted administration of ibuprofen. In addition to the conventional immediate release tablet used as Reference 1, a soft capsule formulation will be applied as Reference 2 (Spalt Forte 400 mg Weichkapseln), as an example for a product with a very fast absorption rate. All 3 immediate release preparations contain 400 mg ibuprofen.
Detailed description
The clinical trial will be performed in a single centre, open-label, randomised (order of treatments), balanced, 3-period, 6-sequence, single dose change-over design with administration under fasting conditions separated by a washout period of at least 2 treatment-free days. Blood sample collection will be performed over 16 h after administration. This time is considered adequate to characterise plasma concentration vs. time profiles long enough for reliable estimation of the extent of absorption, i.e. the AUC derived from measurements is expected to cover at least 80 % of the AUC extrapolated to infinity.
Interventions
DRUGIbuprofen 400 mg oral powder
DRUGIbuprofen 400 mg film-coated tablet
DRUGIbuprofen 400 mg soft capsule
Sponsors
SocraMetrics GmbH
SocraTec R&D GmbH
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. sex: male/female 2. ethnic origin: Caucasian 3. age: 18 years or older 4. body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m², body weight \> 40 kg 5. good state of health 6. non-smoker or ex-smoker for at least 3 months 7. written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial
Exclusion criteria
1. existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient 2. existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient 3. existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient 4. history of gastrointestinal bleeding or perforation, related to previous NSAID therapy 5. existing, or history of, recurrent gastrointestinal ulcer/ bleeding 6. conditions involving an increased tendency to bleeding 7. active or known inflammatory bowel diseases (e.g. colitis ulcerosa, Crohn´s disease) 8. history of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders 9. known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations 10. history of hypersensitivity reactions (e.g. bronchial spasm, asthma, rhinitis, urticaria, or angioedema) after intake of acetylsalicylic acid or other NSAIDs 11. subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator 12. existing, or history of, bronchial asthma, chronic rhinitis or allergic diseases unless it is judged as not relevant for the clinical trial by the investigator 13. subjects with hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption 14. systolic blood pressure \< 90 or \> 145 mmHg 15. diastolic blood pressure \< 60 or \>90 mmHg 16. heart rate \< 50 bpm or \> 90 bpm 17. laboratory values out of normal range unless the deviation from normal is judged as not relevant for the clinical trial by the investigator except parameters ASAT, ALAT, bilirubin and creatinine (see exclusion criterion No. 18) 18. laboratory values: ASAT \> 20 % ULN, ALAT \> 10 % ULN, bilirubin \> 20 % ULN and creatinine \> 9 μmol/l ULN 19. positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test (if positive to be verified by test for HBc-IgM) or anti-HCVtest 20. acute or chronic diseases which may interfere with the pharmacokinetics of the IMP 21. history of or current drug or alcohol dependence 22. positive alcohol or drug test at screening examination 23. regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol for male or ≥ 20 g pure ethanol for female per day 24. subjects who are on a diet which could affect the pharmacokinetics of the active ingredient 25. regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day 26. blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject 27. administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject 28. regular treatment with any systemically available medication (except hormonal contraceptives) 29. subjects, who report a frequent occurrence of migraine attacks 30. positive pregnancy test at screening examination 31. pregnant or lactating women 32. female subjects who do not agree to apply highly effective contraceptive methods 33. subjects suspected or known not to follow instructions 34. subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration versus time curve (AUC0-tlast) for ibuprofen | 16 hours interval |
| Peak Plasma Concentration (Cmax) for ibuprofen | 16 hours interval |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants with treatment-related adverse events | from first dose until discharge of the subject (approx. 2 weeks) |
Countries
Germany
Outcome results
None listed