Trial Outcomes & Findings for Relative Bioavailability of Ibuprofen From a Single Fixed Dose Combination Tablet of Ibuprofen and Caffeine Compared to Single Tablets of Ibuprofen and Ibuprofen Lysinate (NCT NCT01879371)
NCT ID: NCT01879371
Last Updated: 2016-11-16
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
36 participants
Primary outcome timeframe
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
Results posted on
2016-11-16
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
6
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Relative Bioavailability of Ibuprofen From a Single Fixed Dose Combination Tablet of Ibuprofen and Caffeine Compared to Single Tablets of Ibuprofen and Ibuprofen Lysinate
Baseline characteristics by cohort
| Measure |
Ibu + Caf / Ibu Acid / Ibu Lysinate
n=6 Participants
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.
|
Ibu + Caf / Ibu Lysinate / Ibu Acid
n=6 Participants
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.
|
Ibu Acid / Ibu Lysinate/ Ibu + Caf
n=6 Participants
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.
|
Ibu Acid/ Ibu + Caf / Ibu Lysinate
n=6 Participants
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.
|
Ibu Lysinate/ Ibu + Caf / Ibu Acid
n=6 Participants
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.
|
Ibu Lysinate / Ibu Acid / Ibu + Caf
n=6 Participants
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.
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
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Age, Continuous
|
38.7 years
STANDARD_DEVIATION 7.6 • n=99 Participants
|
36.3 years
STANDARD_DEVIATION 3.3 • n=107 Participants
|
42.8 years
STANDARD_DEVIATION 4.5 • n=206 Participants
|
40.2 years
STANDARD_DEVIATION 3.8 • n=7 Participants
|
37.5 years
STANDARD_DEVIATION 9.2 • n=31 Participants
|
38.3 years
STANDARD_DEVIATION 7.1 • n=30 Participants
|
39.0 years
STANDARD_DEVIATION 6.2 • n=3 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
15 Participants
n=3 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
6 Participants
n=30 Participants
|
21 Participants
n=3 Participants
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: Pharmacokinetic set (PKS): included all treated subjects who provided at least one observation for at least one primary Pharmacokinetic endpoint without important protocol violations.
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
Outcome measures
| Measure |
Ibuprofen + Caffeine (FDC) Tablet
n=36 Participants
400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Acid Film-coated Tablet
n=36 Participants
400 mg Ibuprofen acid (Brufen®) film-coated tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Lysinate Film-coated Tablet
n=36 Participants
Ibuprofen lysinate (Nurofen® immedia) film-coated tablet; 400 mg Ibuprofen; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
|---|---|---|---|
|
AUC(0-tz)
|
133 μg*h/mL
Geometric Coefficient of Variation 22.2
|
124 μg*h/mL
Geometric Coefficient of Variation 19.4
|
122 μg*h/mL
Geometric Coefficient of Variation 19.3
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: PKS
Cmax: maximum measured concentration of Ibuprofen in plasma
Outcome measures
| Measure |
Ibuprofen + Caffeine (FDC) Tablet
n=36 Participants
400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Acid Film-coated Tablet
n=36 Participants
400 mg Ibuprofen acid (Brufen®) film-coated tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Lysinate Film-coated Tablet
n=36 Participants
Ibuprofen lysinate (Nurofen® immedia) film-coated tablet; 400 mg Ibuprofen; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
|---|---|---|---|
|
Cmax
|
31.0 μg/mL
Geometric Coefficient of Variation 17.2
|
31.1 μg/mL
Geometric Coefficient of Variation 22.5
|
44.0 μg/mL
Geometric Coefficient of Variation 20.6
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
AUC(0-inf): area under the concentration-time curve of Ibuprofen in plasma over the time interval from 0 extrapolated to infinity
Outcome measures
| Measure |
Ibuprofen + Caffeine (FDC) Tablet
n=35 Participants
400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Acid Film-coated Tablet
n=36 Participants
400 mg Ibuprofen acid (Brufen®) film-coated tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Lysinate Film-coated Tablet
n=36 Participants
Ibuprofen lysinate (Nurofen® immedia) film-coated tablet; 400 mg Ibuprofen; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
|---|---|---|---|
|
AUC(0-inf)
|
135 μg*h/mL
Geometric Coefficient of Variation 21.7
|
127 μg*h/mL
Geometric Coefficient of Variation 20.1
|
125 μg*h/mL
Geometric Coefficient of Variation 20.2
|
Adverse Events
Ibuprofen + Caffeine (FDC) Tablet
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Ibuprofen Acid Film-coated Tablet
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Ibuprofen Lysinate Film-coated Tablet
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ibuprofen + Caffeine (FDC) Tablet
n=36 participants at risk
400 mg Ibuprofen + 100 mg Caffeine fixed dose combination (FDC) tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Acid Film-coated Tablet
n=36 participants at risk
400 mg Ibuprofen acid (Brufen®) film-coated tablet; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
Ibuprofen Lysinate Film-coated Tablet
n=36 participants at risk
Ibuprofen lysinate (Nurofen® immedia) film-coated tablet; 400 mg Ibuprofen; Single dose oral administration of one tablet with 240 mL of water after an overnight fast of at least 10h
|
|---|---|---|---|
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Nervous system disorders
Headache
|
5.6%
2/36 • from up to 21 days prior to first drug administration until 30 days after end of trial, 64 days
|
11.1%
4/36 • from up to 21 days prior to first drug administration until 30 days after end of trial, 64 days
|
2.8%
1/36 • from up to 21 days prior to first drug administration until 30 days after end of trial, 64 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place