Study to Investigate the Relative Bioavailability of Ibuprofen in Healthy Volunteers
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02183012
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
* Study to demonstrate average bioequivalence between a 400 mg ibuprofen extrudate tablet (Test) and a 400 mg ibuprofen lysinate tablet (Dolormin extra ®; reference 1) under fasted conditions.
* Study to determine the relative bioavailability of ibuprofen following single administration of a 400 mg ibuprofen extrudate tablet (Test) compared to a 400 mg ibuprofen tablet (Brufen® 400mg, Denmark; Reference 2) under fasted conditions.
* Study to determine the relative bioavailability of ibuprofen following single administration of a 400 mg ibuprofen extrudate tablet (Test) compared to a 400 mg ibuprofen lysinate tablet (Dolormin extra ®; reference 1) or a 400 mg ibuprofen tablet (Brufen® 400mg, Denmark; Reference 2), respectively, under fed conditions.
* Study to evaluate the effect of food on the pharmacokinetics of ibuprofen for all three formulations.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
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Healthy males and females according to the following criteria:
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Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests:
- No finding deviating from normal and of clinical relevance
- No evidence of a clinically relevant concomitant disease.
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Age ≥ 21 and Age ≤ 50 years
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BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index)
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Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation
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Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
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Surgery of gastrointestinal tract (except appendectomy)
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History of recent surgery including dental surgery
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History of gastrointestinal ulcer or gastrointestinal inflammation (gastritis, ulcerative colitis, Crohn's disease)
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Blood dyscrasias of unknown origin
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Subjects with porphyries diseases
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Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
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History of relevant orthostatic hypotension, fainting spells or blackouts
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Chronic or relevant acute infections
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History of allergy/hypersensitivity/allergic rhinitis (including drug allergy) which is deemed relevant to he trial as judged by the investigator
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Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial except substitution therapy (thyroid, ovaries) and hormonal contraception
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Use of any drugs, which might influence the results of the trial (within 10 days prior to administration or during the trial)
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Participation in another trial with an investigational drug (within two months prior to administration or during the trial)
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Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day)
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Inability to refrain from smoking on trial days
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Alcohol abuse (more than 60 g/day)
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Drug abuse
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Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
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Excessive physical activities (within one week prior to administration or during the trial)
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Any laboratory value outside the reference range of clinical relevance
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Inability to comply with dietary regimen of study centre
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For female subjects:
- Pregnancy
- Positive pregnancy test
- No adequate contraception e.g. oral contraceptives, sterilisation, IUP (intrauterine pessary: in case a IUP was used for contraception, volunteers must be advised to employ additional contraceptive measures (e.g. condom by partner) because prostaglandin inhibition may alter IUP contraceptive efficacy)
- Inability to maintain this adequate contraception during the whole study period
- Lactation period
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description D: Ibuprofen lysinate tablet, fasted state Ibuprofen lysinate - A: Ibuprofen extrudate, fed state Ibuprofen extrudate - B: Ibuprofen extrudate, fasted state Ibuprofen extrudate - C: Ibuprofen lysinate tablet, fed state Ibuprofen lysinate - E: Ibuprofen tablet, fed state Ibuprofen - F: Ibuprofen tablet, fasted state Ibuprofen -
- Primary Outcome Measures
Name Time Method AUC0-∞ (area under the concentration-time curve of the analyte in plasma from zero time to infinity) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 Cmax (maximum observed concentration of the analyte in plasma) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 AUC0-tz (area under the concentration-time curve of the analyte in plasma from zero time to the time of the last quantifiable drug concentration) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5
- Secondary Outcome Measures
Name Time Method tmax (time to reach Cmax) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 t1/2 (terminal half-life of the analyte in plasma) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 Number of patients with adverse events up to 24 days Individual time courses of the ibuprofen plasma concentrations Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 AUCtrunc (Area under the concentration-time curve of the analyte in plasma from zero time to median tmax values of the reference formulation) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 λz (terminal rate constant of the analyte in plasma) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 MRTtot (total mean residence time of the analyte molecules in the body) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 CL/F (total clearance of the analyte in plasma following extravascular administration) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 Vz/F (apparent volume of distribution during the terminal phase λz following extravascular administration) Pre-dose and 15, 30, 45 min, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24 hours after treatment on day 1 of visits 2-5 Number of patients with abnormal changes in laboratory parameters up to 8 days following last drug administration Number of patients with clinically significant changes in vital signs (blood pressure (BP), pulse rate (PR)) up to 8 days following last drug administration Number of patients with abnormal changes in 12-lead electrocardiogram (ECG) up to 8 days following last drug administration Number of patients with abnormal findings in physical examination up to 8 days following last drug administration Assessment of tolerability on a 4-point scale up to 8 days following last drug administration