Trial Outcomes & Findings for To Determine Blood Concentrations of Ibuprofen and Caffeine in a Tablet Against Ibuprofen Alone From Another Tablet (NCT NCT02629354)

NCT ID: NCT02629354

Last Updated: 2017-05-05

Results Overview

This outcome measure presents the maximum observed concentration (Cmax) of S-ibuprofen in plasma obtained directly from the concentration-time data.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Results posted on

2017-05-05

Participant Flow

All subjects were screened for eligibility to participate in the trial. Subjects attended a specialist site ensured that they (the subjects) met all inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were violated.

Participant milestones

Participant milestones
Measure	Ref - Test Subjects received the reference product (Ref) which was a single oral dose (1 film-coated tablet) of 400 milligram (mg) ibuprofen (equivalent to 684 mg ibuprofen lysinate, trade name: Dolormin® Extra) under fed conditions. After a washout period of at least 6 calendar days, the subjects received the test product (Test), which was a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine in a film coated tablet as a fixed dose combination (FDC), under fed conditions. Finally the subjects had a follow-up phase of 72 hours.	Test - Ref Subjects received the test product (Test) which was a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine in a film coated tablet as a FDC under fed conditions. After a washout period of at least 6 calendar days, the subjects received the reference product (Ref), which was a single oral dose (1 film-coated tablet) of 400 milligram (mg) ibuprofen (equivalent to 684 mg ibuprofen lysinate, trade name: Dolormin® Extra), under fed conditions. Finally the subjects had a follow-up phase of 72 hours.
Period 1 STARTED	18	18
Period 1 COMPLETED	18	18
Period 1 NOT COMPLETED	0	0
Washout Period STARTED	18	18
Washout Period COMPLETED	18	18
Washout Period NOT COMPLETED	0	0
Period 2 STARTED	18	18
Period 2 COMPLETED	18	18
Period 2 NOT COMPLETED	0	0
Follow-up STARTED	18	18
Follow-up COMPLETED	18	18
Follow-up NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

To Determine Blood Concentrations of Ibuprofen and Caffeine in a Tablet Against Ibuprofen Alone From Another Tablet

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ref - Test n=18 Participants Subjects received the reference product (Ref) which was a single oral dose (1 film-coated tablet) of 400 milligram (mg) ibuprofen (equivalent to 684 mg ibuprofen lysinate, trade name: Dolormin® Extra) under fed conditions. After a washout period of at least 6 calendar days, the subjects received the test product (Test), which was a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine in a film coated tablet as a fixed dose combination (FDC), under fed conditions. Finally the subjects had a follow-up phase of 72 hours.	Test - Ref n=18 Participants Subjects received the test product (Test) which was a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine in a film coated tablet as a FDC under fed conditions. After a washout period of at least 6 calendar days, the subjects received the reference product (Ref), which was a single oral dose (1 film-coated tablet) of 400 milligram (mg) ibuprofen (equivalent to 684 mg ibuprofen lysinate, trade name: Dolormin® Extra), under fed conditions. Finally the subjects had a follow-up phase of 72 hours.	Total n=36 Participants Total of all reporting groups
Age, Continuous	29.8 years STANDARD_DEVIATION 8.49 • n=5 Participants	26.1 years STANDARD_DEVIATION 5.59 • n=7 Participants	28.0 years STANDARD_DEVIATION 7.33 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	13 Participants n=7 Participants	25 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: Pharmacokinetic (PK) population: all subjects who completed the PK sampling in both periods and with no major protocol deviations considered to impact on the analysis of the PK data were included.

This outcome measure presents the maximum observed concentration (Cmax) of S-ibuprofen in plasma obtained directly from the concentration-time data.

Outcome measures

Outcome measures
Measure	Reference Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Maximum Observed Plasma Concentration (Cmax) of S-ibuprofen	13268.7 nanogram (ng)/ millilitre (mL) Geometric Coefficient of Variation 38.0	14967.2 nanogram (ng)/ millilitre (mL) Geometric Coefficient of Variation 34.9

PRIMARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the Cmax of R-ibuprofen in plasma obtained directly from the concentration-time data.

Outcome measures

Outcome measures
Measure	Reference Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Cmax of R-ibuprofen	10495.7 ng/mL Geometric Coefficient of Variation 32.7	11454.6 ng/mL Geometric Coefficient of Variation 26.6

PRIMARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the Cmax of ibuprofen in plasma obtained directly from the concentration-time data.

Outcome measures

Outcome measures
Measure	Reference Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Cmax of Ibuprofen	23557.9 ng/mL Geometric Coefficient of Variation 34.8	26309.5 ng/mL Geometric Coefficient of Variation 30.3

PRIMARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the area under the plasma concentration of S-ibuprofen versus time curve, from time zero to t, where t is the time of the last quantifiable concentration (AUC0-t).

Outcome measures

Outcome measures
Measure	Reference Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, From Time Zero to t (AUC0-t)	65110 hour (h)*ng/mL Geometric Coefficient of Variation 21.9	63150 hour (h)*ng/mL Geometric Coefficient of Variation 21.7

PRIMARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the area under the plasma concentration of R-ibuprofen versus time curve, from time zero to t, where t is the time of the last quantifiable concentration (AUC0-t).

Outcome measures

Outcome measures
Measure	Reference Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
AUC0-t of R-ibuprofen	42480 h*ng/mL Geometric Coefficient of Variation 19.0	41200 h*ng/mL Geometric Coefficient of Variation 15.9

PRIMARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the area under the plasma concentration of ibuprofen versus time curve, from time zero to t, where t is the time of the last quantifiable concentration (AUC0-t).

Outcome measures

Outcome measures
Measure	Reference Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
AUC0-t of Ibuprofen	108400 h*ng/mL Geometric Coefficient of Variation 18.4	105300 h*ng/mL Geometric Coefficient of Variation 16.9

SECONDARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the area under the plasma concentration of S-ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).

Outcome measures

Outcome measures
Measure	Reference Product n=25 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, With Extrapolation to Infinity (AUC0-INF)	68900 h*ng/mL Geometric Coefficient of Variation 17.2	64990 h*ng/mL Geometric Coefficient of Variation 20.6

SECONDARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the area under the plasma concentration of R-ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).

Outcome measures

Outcome measures
Measure	Reference Product n=25 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
AUC0-INF of R-ibuprofen	43910 h*ng/mL Geometric Coefficient of Variation 17.2	41960 h*ng/mL Geometric Coefficient of Variation 16.3

SECONDARY outcome

Timeframe: Within 2 hours prior to dosing and at 5, 10,15, 30 and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hours post-dose

Population: PK population

This outcome measure presents the area under the plasma concentration of ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).

Outcome measures

Outcome measures
Measure	Reference Product n=25 Participants Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.	Test Product n=26 Participants Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
AUC0-INF of Ibuprofen	113200 h*ng/mL Geometric Coefficient of Variation 14.6	107300 h*ng/mL Geometric Coefficient of Variation 16.4

Adverse Events

Reference Product

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Test Product

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER