Clinical trial NCT02183012: Study to Investigate the Relative Bioavailability of Ibuprofen in Healthy Volunteers
Official title: Open-label, Randomised, Single Dose, Four-way Crossover Study to Investigate the Relative Bioavailability of a 400 mg Ibuprofen Extrudate Tablet Compared to a 400 mg Ibuprofen Lysinate Tablet (Dolormin Extra®) and a 400 mg Ibuprofen Tablet (Brufen® 400 mg, Denmark) in Fasted Condition and After Ingestion of a Standardised Meal in Healthy Male and Female Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 36
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: AUC0-∞ (area under the concentration-time curve of the analyte in plasma from zero time to infinity)
timeFrame: 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
measure: Cmax (maximum observed concentration of the analyte in plasma)
timeFrame: 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
measure: 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)
timeFrame: 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 outcomes:
measure: Individual time courses of the ibuprofen plasma concentrations
timeFrame: 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
measure: AUCtrunc (Area under the concentration-time curve of the analyte in plasma from zero time to median tmax values of the reference formulation)
timeFrame: 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
measure: tmax (time to reach Cmax)
timeFrame: 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
measure: t1/2 (terminal half-life of the analyte in plasma)
timeFrame: 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
measure: λz (terminal rate constant of the analyte in plasma)
timeFrame: 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
measure: MRTtot (total mean residence time of the analyte molecules in the body)
timeFrame: 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
measure: CL/F (total clearance of the analyte in plasma following extravascular administration)
timeFrame: 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
measure: Vz/F (apparent volume of distribution during the terminal phase λz following extravascular administration)
timeFrame: 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
measure: Number of patients with adverse events
timeFrame: up to 24 days
measure: Number of patients with abnormal changes in laboratory parameters
timeFrame: up to 8 days following last drug administration
measure: Number of patients with clinically significant changes in vital signs (blood pressure (BP), pulse rate (PR))
timeFrame: up to 8 days following last drug administration
measure: Number of patients with abnormal changes in 12-lead electrocardiogram (ECG)
timeFrame: up to 8 days following last drug administration
measure: Number of patients with abnormal findings in physical examination
timeFrame: up to 8 days following last drug administration
measure: Assessment of tolerability on a 4-point scale
timeFrame: up to 8 days following last drug administration
Other outcomes:
Locations:
Study officials:
References: