Study to Investigate the Relative Bioavailability of Ibuprofen in Healthy Volunteers

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 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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ibuprofen; Drug: Ibuprofen extrudate; Drug: Ibuprofen lysinate

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: Ibuprofen extrudate, fed state	Drug: Ibuprofen extrudate
Experimental: B: Ibuprofen extrudate, fasted state	Drug: Ibuprofen extrudate
Active Comparator: C: Ibuprofen lysinate tablet, fed state	Drug: Ibuprofen lysinate
Active Comparator: D: Ibuprofen lysinate tablet, fasted state	Drug: Ibuprofen lysinate
Active Comparator: E: Ibuprofen tablet, fed state	Drug: Ibuprofen
Active Comparator: F: Ibuprofen tablet, fasted state	Drug: Ibuprofen

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2002
• Primary Completion (Actual): October 1, 2002

Study Registration Dates

• First Submitted: July 4, 2014
• First Submitted That Met QC Criteria: July 4, 2014
• First Posted (Estimate): July 8, 2014

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 4, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: 1024.5