To Determine Blood Concentrations of Ibuprofen and Caffei... | NCT02629354

NCT02629354

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
Ibuprofen and Caffeine	Experimental		Drug: Ibuprofen Drug: Caffeine
Ibuprofen	Active Comparator		Drug: Ibuprofen

Name	Type	Description	Arm Group Labels	Other Names
Ibuprofen	Drug		Ibuprofen and Caffeine
Caffeine

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of S-ibuprofen	This outcome measure presents the maximum observed concentration (Cmax) of S-ibuprofen in plasma obtained directly from the concentration-time data.	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
Cmax of R-ibuprofen	This outcome measure presents the Cmax of R-ibuprofen in plasma obtained directly from the concentration-time data.	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
Cmax of Ibuprofen	This outcome measure presents the Cmax of ibuprofen in plasma obtained directly from the concentration-time data.	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
Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, From Time Zero to t (AUC0-t)	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).	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
AUC0-t of R-ibuprofen	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).	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

Secondary Outcomes

Measure	Description	Time Frame
Area Under the Plasma Concentration of S-ibuprofen Versus Time Curve, With Extrapolation to Infinity (AUC0-INF)	This outcome measure presents the area under the plasma concentration of S-ibuprofen versus time curve, with extrapolation to infinity (AUC0-INF).	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

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Healthy males and females, 18 to 50 years (inclusive) at time of screening.
Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 (inclusive).
Body mass not less than 50 kg.
Medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be clinically acceptable or within laboratory reference ranges for the relevant laboratory tests, unless the PI considers the deviation to be irrelevant for the purpose of the study.
Non-smokers and mild or moderate smokers (<= 10 cigarettes or pipes per day). Further inclusion criteria apply

Exclusion criteria:

Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol per week for females. One unit is equal to beer [200 mL/10 ounces], wine [100 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
Regular exposure to substances of abuse (other than alcohol) within the past year.
Use of any medication, prescribed or over-the-counter or herbal remedies, within 2 weeks before the first administration of IMP except if this will not affect the outcome of the study in the opinion of the PI. In this study the concomitant use of hormonal contraceptives is allowed.
Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 5 elimination half-lives for chemical entities or 2 elimination half-lives for anti-bodies or insulin), whichever is the longer) before administration of IMP in this study, at the discretion of the PI.
Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system.
History of hypersensitivity or allergy (angioedema or urticaria) to the IMP or its excipients or any related medication (Aspirin or any other NSAID).
Diagnosis of hypotension made during the screening period.
Diagnosis of hypertension made during the screening period or current diagnosis of hypertension.
Resting pulse of > 100 beats per minute or < 40 beats per minute during the screening period, either supine or standing.
Renal impairment.
Positive urine screen for drugs of abuse. In case of a positive result the urine screen for drugs of abuse may be repeated once at the discretion of the PI.

Further exclusion criteria apply

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Observed Plasma Concentration (Cmax) of S-ibuprofen

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

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram (ng)/ millilitre (mL)

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

ID	Title	Description
OG000	Reference Product	Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.
OG001

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Reference Product	Subjects received a single oral dose of 400 mg ibuprofen (trade name: Dolormin® Extra), under fed condition.

ID	Term
D010666	Phenylpropionates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals