Bioequivalence study of a new ibuprofen arginine 600 mg tablet formulation versus ibuprofen arginine 600 mg sachet Not Applicable
Conditions
Interventions
A single oral dose of 600 mg of ibuprofen arginine, as a film-coated tablet (test product) and granules for oral solution (reference product), will be administered to healthy men and women, under fast
reference/test) according to the randomisation list, to receive one of the two treatments (test or reference) during period 1 and the other one during period 2.
The randomisation number will be give
Sponsors
Zambon (Italy)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent: subjects able to complete and sign the informed consent before inclusion in the study 2. Sex and age: men and women, 18-55 years old inclusive 3. Body Mass Index: 18.5-30 kg/m² inclusive 4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 60-89 mmHg, heart rate 50-90 bpm, measured after 5 min at rest in the sitting position 5. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the Investigator and to comply with the requirements of the entire study 6. Contraception and fertility (women only): women of child-bearing potential must be using at least one of the following reliable methods of contraception: 6.1. Hormonal oral, implantable, transdermal or injectable contraceptives for at least 2 months before the screening visit 6.2. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit 6.3. A male sexual partner who agrees to use a male condom with spermicide 6.4. A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all women, pregnancy test results must be negative at screening and Day -1.
Exclusion criteria
Exclusion criteria: 1. Subjects: subjects younger than 18 years or older than 55 years, subjects unable to give informed consent, subjects with cognitive impairment and otherwise non-healthy subjects 2. SARS-CoV-2 test: positive on COVID-19 Antigen Rapid Test at screening or Day -1 3. Electrocardiogram (12-lead ECG in supine position): clinically significant abnormalities 4. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study 5. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness 6. Allergy: ascertained or presumptive hypersensitivity to the active principle or formulations' ingredients or both; history of anaphylaxis to drugs or allergic reactions in general (in particular to NSAIDs), which the Investigator considers may affect the outcome of the study 7. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine, immunological or neurological diseases that may interfere with the aim of the study 8. Medications: medications, including over-the-counter (OTC) medications, herbal remedies and vitamins, for 2 weeks before the start of the study. Hormonal contraceptives for women will be allowed 9. Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study 10. Blood donation: blood donations for 3 months before this study 11. Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for women and >2 drinks/day for men, defined according to the USDA Dietary Guidelines 2020-2025], caffeine (>5 cups coffee/tea/day) or tobacco abuse (>10 cigarettes/day) 12. Drug test: positive result at the drug test at screening or Day -1 13. Alcohol test: positive alcohol test on Day -1 14. Diet: abnormal diets (3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians 15. Pregnancy (women only): positive or missing pregnancy test at screening or Day -1, pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rate (Cmax, maximum plasma concentration) and extent (AUC0-t, area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method) of absorption of ibuprofen S-enantiomer calculated from plasma concentrations after a single oral dose of test and reference products. Plasma concentrations of ibuprofen S-enantiomer will be measured using a fully validated chiral LC-MS/MS method at pre-dose (0) and at 5, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 3, 4, 6, 9, 12 h post-dose in each of the two study periods. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. tmax (time to achieve the maximum plasma concentration), Frel (relative bioavailability, calculated as ratio AUC0-t [test]/AUC0-t [reference]) and, if feasible, %AUCextra (percentage of the residual area extrapolated to infinity in relation to the total AUC0-inf calculated, if feasible, as 100×[Ct/ ?Z]/AUC0-inf), AUC0-inf (area under the concentration-time curve extrapolated to infinity calculated, if feasible, as AUC0-t + Ct/?z, where Ct is the last measurable drug concentration), t1/2 (half-life calculated, if feasible, as ln2/?z) and ?Z (terminal elimination rate constant, calculated, if feasible, by log-linear regression using at least 3 points) of plasma ibuprofen S-enantiomer after single oral dose of test and reference products 2. Cmax, AUC0-t, tmax, Frel and, if feasible, %AUCextra, AUC0-inf, t1/2 and ?Z of plasma ibuprofen R-enantiomer after a single oral dose of test and reference products 3. Cmax, AUC0-t, tmax, Frel and, if feasible, %AUCextra, AUC0-inf, t1/2 and ?Z of total ibuprofen, calculated as the sum of ibuprofen S-enantiomer and R-enantiomer concentrations, after a single oral dose of test and reference products 4. Treatment-emergent adverse events during the whole clinical study, vital signs (blood pressure and heart rate, measured at screening visit, on Day -1 of each study period, On Day 1 at 12 h post-dose of each study period and at early termination visit), physical examinations (at screening and at final visit/early termination visit), body weight (at screening and at final visit/early termination visit), clinical laboratory parameters (at screening, on Day -1 of each study period and at final visit/early termination visit). Plasma concentrations of ibuprofen S-enantiomer and ibuprofen R-enantiomer will be measured using a fully validated chiral LC-MS/MS method at pre-dose (0) and at 5, 10, 20, 30, 40, 50 min and 1, 1.5, 2, 3, 4, 6, 9, 12 h post-dose in each of the two study periods. | — |
Countries
Switzerland
Contacts
Public ContactVeronica Di Fonzo
Outcome results
None listed