Healthy
Conditions
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.
Interventions
DRUGIbuprofen extrudate
DRUGIbuprofen lysinate
DRUGIbuprofen
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males and females according to the following criteria: * 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. * Age ≥ 21 and Age ≤ 50 years * BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index) * Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation
Exclusion criteria
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Surgery of gastrointestinal tract (except appendectomy) * History of recent surgery including dental surgery * History of gastrointestinal ulcer or gastrointestinal inflammation (gastritis, ulcerative colitis, Crohn's disease) * Blood dyscrasias of unknown origin * Subjects with porphyries diseases * Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders * History of relevant orthostatic hypotension, fainting spells or blackouts * Chronic or relevant acute infections * History of allergy/hypersensitivity/allergic rhinitis (including drug allergy) which is deemed relevant to he trial as judged by the investigator * 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 * Use of any drugs, which might influence the results of the trial (within 10 days prior to administration or during the trial) * Participation in another trial with an investigational drug (within two months prior to administration or during the trial) * Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day) * Inability to refrain from smoking on trial days * Alcohol abuse (more than 60 g/day) * Drug abuse * Blood donation (more than 100 mL within four weeks prior to administration or during the trial) * Excessive physical activities (within one week prior to administration or during the trial) * Any laboratory value outside the reference range of clinical relevance * Inability to comply with dietary regimen of study centre * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| Number of patients with adverse events | up to 24 days |
| 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 |
| 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 |
Outcome results
None listed