Healthy
Conditions
Brief summary
To investigate the relative bioavailability of ibuprofen from a (FDC) film-coated tablet of ibuprofen and caffeine vs. a tablet of ibuprofen (Brufen®) and a tablet of ibuprofen lysinate (Nurofen Immedia®).
Interventions
DRUGIbuprofen+caffeine FDC
oral dose
DRUGIbuprofen (Nurofen Immedia®)
oral dose
oral dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects * Age 18 to 50 years * Body mass index (BMI) 18.5 to 29.9 kg/m2 * Subjects must be able to understand and comply with study requirements
Exclusion criteria
\- Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-tz) | 2 hours (h) before drug administration and 5minutes (min), 10min, 15min, 30min, 45min, 1h, 1h 15min, 1h 30min, 1h 45min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h after drug administration | AUC(0-tz): area under the concentration-time curve of Ibuprofen in plasma over the time interval from 0 to the last quantifiable data point |
| Cmax | 2 hours (h) before drug administration and 5minutes (min), 10min, 15min, 30min, 45min, 1h, 1h 15min, 1h 30min, 1h 45min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h after drug administration | Cmax: maximum measured concentration of Ibuprofen in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-inf) | 2 hours (h) before drug administration and 5minutes (min), 10min, 15min, 30min, 45min, 1h, 1h 15min, 1h 30min, 1h 45min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h after drug administration | AUC(0-inf): area under the concentration-time curve of Ibuprofen in plasma over the time interval from 0 extrapolated to infinity |
Countries
Germany
Participant flow
Recruitment details
36 healthy male and female subjects (at least a third of each sex) were recruited from the volunteers' pool of the Human Pharmacology centre of BI Pharma GmbH & Co. KG, Ingelheim, Germany.
Participants by arm
| Arm | Count |
|---|---|
| Ibu + Caf / Ibu Acid / Ibu Lysinate Participants first received Treatment T (400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet). After a washout phase of at least 6 days, they then received Treatment R1 (400mg Ibuprofen acid (Brufen®) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment R2 (400mg Ibuprofen lysinate (Nurofen® immedia) film-coated tablet). Every treatment is given oral as single dose of one tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| Ibu + Caf / Ibu Lysinate / Ibu Acid Participants first received Treatment T (400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet). After a washout phase of at least 6 days, they then received Treatment R2 (400mg Ibuprofen lysinate (Nurofen® immedia) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment R1 (400mg Ibuprofen acid (Brufen®) film-coated tablet). Every treatment is given oral as single dose of one tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| Ibu Acid / Ibu Lysinate/ Ibu + Caf Participants first received Treatment R1 (400mg Ibuprofen acid (Brufen®) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment R2 (400mg Ibuprofen lysinate (Nurofen® immedia) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment T (400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet). Every treatment is given oral as single dose of one tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| Ibu Acid/ Ibu + Caf / Ibu Lysinate Participants first received Treatment R1 (400mg Ibuprofen acid (Brufen®) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment T (400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet). After a washout phase of at least 6 days, they then received Treatment R2 (400mg Ibuprofen lysinate (Nurofen® immedia) film-coated tablet). Every treatment is given oral as single dose of one tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| Ibu Lysinate/ Ibu + Caf / Ibu Acid Participants first received Treatment R2 (400mg Ibuprofen lysinate (Nurofen® immedia) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment T (400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet). After a washout phase of at least 6 days, they then received Treatment R1 (400mg Ibuprofen acid (Brufen®) film-coated tablet). Every treatment is given oral as single dose of one tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| Ibu Lysinate / Ibu Acid / Ibu + Caf Participants first received Treatment R2 (400mg Ibuprofen lysinate (Nurofen® immedia) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment R1 (400mg Ibuprofen acid (Brufen®) film-coated tablet). After a washout phase of at least 6 days, they then received Treatment T (400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet). Every treatment is given oral as single dose of one tablet with 240 mL of water after an overnight fast of at least 10 h. | 6 |
| Total | 36 |
Baseline characteristics
| Characteristic | Ibu + Caf / Ibu Acid / Ibu Lysinate | Ibu + Caf / Ibu Lysinate / Ibu Acid | Ibu Acid / Ibu Lysinate/ Ibu + Caf | Ibu Acid/ Ibu + Caf / Ibu Lysinate | Ibu Lysinate/ Ibu + Caf / Ibu Acid | Ibu Lysinate / Ibu Acid / Ibu + Caf | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.7 years STANDARD_DEVIATION 7.6 | 36.3 years STANDARD_DEVIATION 3.3 | 42.8 years STANDARD_DEVIATION 4.5 | 40.2 years STANDARD_DEVIATION 3.8 | 37.5 years STANDARD_DEVIATION 9.2 | 38.3 years STANDARD_DEVIATION 7.1 | 39.0 years STANDARD_DEVIATION 6.2 |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 0 Participants | 15 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 6 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 36 | 4 / 36 | 1 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 36 |
Outcome results
Primary
AUC(0-tz)
AUC(0-tz): area under the concentration-time curve of Ibuprofen in plasma over the time interval from 0 to the last quantifiable data point
Time frame: 2 hours (h) before drug administration and 5minutes (min), 10min, 15min, 30min, 45min, 1h, 1h 15min, 1h 30min, 1h 45min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h after drug administration
Population: Pharmacokinetic set (PKS): included all treated subjects who provided at least one observation for at least one primary Pharmacokinetic endpoint without important protocol violations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen + Caffeine (FDC) Tablet | AUC(0-tz) | 133 μg*h/mL | Geometric Coefficient of Variation 22.2 |
| Ibuprofen Acid Film-coated Tablet | AUC(0-tz) | 124 μg*h/mL | Geometric Coefficient of Variation 19.4 |
| Ibuprofen Lysinate Film-coated Tablet | AUC(0-tz) | 122 μg*h/mL | Geometric Coefficient of Variation 19.3 |
Comparison: The ANOVA (analysis of variance) model on the logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect.~The main focus was on estimation and not on testing, that is, formal statistical hypotheses were not tested.90% CI: [105.334, 110.431]
Comparison: The ANOVA (analysis of variance) model on the logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. The main focus was on estimation and not on testing, that is, formal statistical hypotheses were not tested.90% CI: [107.072, 111.936]
Primary
Cmax
Cmax: maximum measured concentration of Ibuprofen in plasma
Time frame: 2 hours (h) before drug administration and 5minutes (min), 10min, 15min, 30min, 45min, 1h, 1h 15min, 1h 30min, 1h 45min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen + Caffeine (FDC) Tablet | Cmax | 31.0 μg/mL | Geometric Coefficient of Variation 17.2 |
| Ibuprofen Acid Film-coated Tablet | Cmax | 31.1 μg/mL | Geometric Coefficient of Variation 22.5 |
| Ibuprofen Lysinate Film-coated Tablet | Cmax | 44.0 μg/mL | Geometric Coefficient of Variation 20.6 |
Comparison: The ANOVA (analysis of variance) model on the logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. The main focus was on estimation and not on testing, that is, formal statistical hypotheses were not tested.90% CI: [93.874, 105.776]
Comparison: The ANOVA (analysis of variance) model on the logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. The main focus was on estimation and not on testing, that is, formal statistical hypotheses were not tested.90% CI: [67.087, 73.928]
Secondary
AUC(0-inf)
AUC(0-inf): area under the concentration-time curve of Ibuprofen in plasma over the time interval from 0 extrapolated to infinity
Time frame: 2 hours (h) before drug administration and 5minutes (min), 10min, 15min, 30min, 45min, 1h, 1h 15min, 1h 30min, 1h 45min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h, 34h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Ibuprofen + Caffeine (FDC) Tablet | AUC(0-inf) | 135 μg*h/mL | Geometric Coefficient of Variation 21.7 |
| Ibuprofen Acid Film-coated Tablet | AUC(0-inf) | 127 μg*h/mL | Geometric Coefficient of Variation 20.1 |
| Ibuprofen Lysinate Film-coated Tablet | AUC(0-inf) | 125 μg*h/mL | Geometric Coefficient of Variation 20.2 |
Comparison: The ANOVA (analysis of variance) model on the logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. The main focus was on estimation and not on testing, that is, formal statistical hypotheses were not tested.90% CI: [104.05, 109.004]
Comparison: The ANOVA (analysis of variance) model on the logarithmic scale included effects accounting for the following sources of variation: 'sequence', 'period' and 'treatment' as fixed effects and 'subjects within sequences' as random effect. The main focus was on estimation and not on testing, that is, formal statistical hypotheses were not tested.90% CI: [106.185, 111.054]