Ibuprofen Bioavailability Trial With Oral Single Dose Administration.

Study Overview
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Brief Summary
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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
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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.

Official Title
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Characterisation of Relative Bioavailability of a Newly Developed Ibuprofen Oral Powder Formulation in Comparison With Two Marketed Reference Products in a Single Dose, 3-period-crossover Design Under Fasting Conditions; Controlled, Open-label, Randomised Study With Bioequivalence Assessment

Conditions
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Bioequivalence

Intervention / Treatment
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* Drug: Ibuprofen 400 mg oral powder
* Drug: Ibuprofen 400 mg film-coated tablet
* Drug: Ibuprofen 400 mg soft capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sex: male/female ethnic origin: Caucasian age: 18 years or older body-mass index (BMI): ≥ 18.5 kg/m² and ≤ 30.0 kg/m², body weight > 40 kg good state of health non-smoker or ex-smoker for at least 3 months 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: existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient history of gastrointestinal bleeding or perforation, related to previous NSAID therapy existing, or history of, recurrent gastrointestinal ulcer/ bleeding conditions involving an increased tendency to bleeding active or known inflammatory bowel diseases (e.g. colitis ulcerosa, Crohn´s disease) history of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations history of hypersensitivity reactions (e.g. bronchial spasm, asthma, rhinitis, urticaria, or angioedema) after intake of acetylsalicylic acid or other NSAIDs subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator 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 subjects with hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption systolic blood pressure < 90 or > 145 mmHg diastolic blood pressure < 60 or >90 mmHg heart rate < 50 bpm or > 90 bpm 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) laboratory values: ASAT > 20 % ULN, ALAT > 10 % ULN, bilirubin > 20 % ULN and creatinine > 9 μmol/l ULN 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 acute or chronic diseases which may interfere with the pharmacokinetics of the IMP history of or current drug or alcohol dependence positive alcohol or drug test at screening examination regular intake of alcoholic food or beverages of ≥ 40 g pure ethanol for male or ≥ 20 g pure ethanol for female per day subjects who are on a diet which could affect the pharmacokinetics of the active ingredient regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day blood donation or other blood loss of more than 400 ml within the last 2 months prior to individual enrolment of the subject administration of any investigational medicinal product during the last 2 months prior to individual enrolment of the subject regular treatment with any systemically available medication (except hormonal contraceptives) subjects, who report a frequent occurrence of migraine attacks positive pregnancy test at screening examination pregnant or lactating women female subjects who do not agree to apply highly effective contraceptive methods subjects suspected or known not to follow instructions 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ibuprofen 400 mg oral powder<br>oral fasted administration of 1 sachet of Ibuprofen 400 mg oral powder (Hermes Arzneimittel GmbH, Germany), containing 400 mg ibuprofen | Drug: Ibuprofen 400 mg oral powder<br> <br> |
| Active Comparator: Brufen 400 mg film-coated tablets<br>oral fasted administration of Brufen 400 mg film-coated tablets (Abbott Scandinavia AB, Sweden), containing 400 mg ibuprofen | Drug: Ibuprofen 400 mg film-coated tablet<br> <br> |
| Active Comparator: Spalt forte 400 mg Weichkapseln<br>oral fasted administration of Spalt forte 400 mg Weichkapseln (Pfizer Consumer Healthcare GmbH, Germany), containing 400 mg ibuprofen | Drug: Ibuprofen 400 mg soft capsule<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events |  | from first dose until discharge of the subject (approx. 2 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Healthy, Bioavailability, Ibuprofen