Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02629354
Recruitment Status : Completed
First Posted : December 14, 2015
Results First Posted : March 16, 2017
Last Update Posted : May 5, 2017
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Ibuprofen
Drug: Caffeine
Enrollment 36
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Ref - Test Test - Ref
Hide Arm/Group Description 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. 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 Title: Period 1
Started 18 18
Completed 18 18
Not Completed 0 0
Period Title: Washout Period
Started 18 18
Completed 18 18
Not Completed 0 0
Period Title: Period 2
Started 18 18
Completed 18 18
Not Completed 0 0
Period Title: Follow-up
Started 18 18
Completed 18 18
Not Completed 0 0
Arm/Group Title Ref - Test Test - Ref Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 18 18 36
Hide Baseline Analysis Population Description
Randomized population: all subjects randomized to a treatment sequence.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants 18 participants 36 participants
29.8  (8.49) 26.1  (5.59) 28.0  (7.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants 18 participants 36 participants
Female
6
  33.3%
5
  27.8%
11
  30.6%
Male
12
  66.7%
13
  72.2%
25
  69.4%
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of S-ibuprofen
Hide Description This outcome measure presents the maximum observed concentration (Cmax) of S-ibuprofen in plasma obtained directly from the concentration-time data.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 26 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram (ng)/ millilitre (mL)
13268.7
(38.0%)
14967.2
(34.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% confidence interval (CI) was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 113.77
Confidence Interval (2-Sided) 90%
98.99 to 130.75
Estimation Comments Analysis of variance (ANOVA) with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
2.Primary Outcome
Title Cmax of R-ibuprofen
Hide Description This outcome measure presents the Cmax of R-ibuprofen in plasma obtained directly from the concentration-time data.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 26 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
10495.7
(32.7%)
11454.6
(26.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 110.16
Confidence Interval (2-Sided) 90%
96.32 to 125.97
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
3.Primary Outcome
Title Cmax of Ibuprofen
Hide Description This outcome measure presents the Cmax of ibuprofen in plasma obtained directly from the concentration-time data.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 26 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
23557.9
(34.8%)
26309.5
(30.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 112.69
Confidence Interval (2-Sided) 90%
98.49 to 128.94
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
4.Primary Outcome
Title Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, From Time Zero to t (AUC0-t)
Hide Description 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).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 26 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hour (h)*ng/mL
65110
(21.9%)
63150
(21.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 97.36
Confidence Interval (2-Sided) 90%
94.61 to 100.19
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
5.Primary Outcome
Title AUC0-t of R-ibuprofen
Hide Description 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).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 26 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
42480
(19.0%)
41200
(15.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 97.55
Confidence Interval (2-Sided) 90%
92.57 to 102.80
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
6.Primary Outcome
Title AUC0-t of Ibuprofen
Hide Description 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).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 26 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
108400
(18.4%)
105300
(16.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 97.57
Confidence Interval (2-Sided) 90%
94.50 to 100.73
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
7.Secondary Outcome
Title Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, With Extrapolation to Infinity (AUC0-INF)
Hide Description This outcome measure presents the area under the plasma concentration of S-ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 25 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
68900
(17.2%)
64990
(20.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 96.47
Confidence Interval (2-Sided) 90%
93.74 to 99.28
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
8.Secondary Outcome
Title AUC0-INF of R-ibuprofen
Hide Description This outcome measure presents the area under the plasma concentration of R-ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 25 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
43910
(17.2%)
41960
(16.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 97.21
Confidence Interval (2-Sided) 90%
92.22 to 102.46
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
9.Secondary Outcome
Title AUC0-INF of Ibuprofen
Hide Description This outcome measure presents the area under the plasma concentration of ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
PK population
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description:
Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
Overall Number of Participants Analyzed 25 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
113200
(14.6%)
107300
(16.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Reference Product, Test Product
Comments Relative bioavailability [%] was estimated by the ratios of the geometric means (100*test/reference [T/R]). Additionally, it's two-sided 90% CI was provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Percent Ratio Test/Ref
Estimated Value 96.83
Confidence Interval (2-Sided) 90%
93.75 to 100.01
Estimation Comments ANOVA with fixed effects for sequence, subject nested within sequence, period and product after logarithmic transformation of the data.
Time Frame From first administration of study medication until 3 days after last dosing (up to 11 days).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Reference Product Test Product
Hide Arm/Group Description Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition. Subjects received a single oral dose of 400 mg ibuprofen acid and 100 mg caffeine as a FDC under fed condition.
All-Cause Mortality
Reference Product Test Product
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Reference Product Test Product
Affected / at Risk (%) Affected / at Risk (%)
Total   0/36 (0.00%)   0/36 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Reference Product Test Product
Affected / at Risk (%) Affected / at Risk (%)
Total   0/36 (0.00%)   0/36 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02629354     History of Changes
Other Study ID Numbers: 1335.3
First Submitted: December 10, 2015
First Posted: December 14, 2015
Results First Submitted: January 27, 2017
Results First Posted: March 16, 2017
Last Update Posted: May 5, 2017