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Clinical Trial Results:
A SINGLE-DOSE, RANDOMIZED, TWO-PERIOD, CROSSOVER STUDY TO ASSESS BIOEQUIVALENCE BETWEEN TWO IBUPROFEN 200 MG TABLET FORMULATIONS, IN HEALTHY ADULTS

Summary
EudraCT number	2013-001442-34
Trial protocol	SE
Global end of trial date	24 Sep 2013

Results information
Results version number	v1(current)
This version publication date	13 Jul 2016
First version publication date	03 Aug 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

IBUPAI0002

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

McNeil AB

Sponsor organisation address

Box 941, Norrbroplatsen 2, Helsingborg, Sweden, SE-251 09

Public contact

Elisabeth Kruse, McNeil AB, +46 42 288555, EKruse@its.jnj.com

Scientific contact

Maj Ablad-Jacobson, McNeil AB, +46 42 289374, MAbladJa@its.jnj.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

31 Jan 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

24 Sep 2013

Global end of trial reached?

Yes

Global end of trial date

24 Sep 2013

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to show bioequivalence between Ipren film coated tablet 200 mg and Brufen film coated tablet 200 mg, with respect to the single-dose pharmacokinetics of S-(+) ibuprofen. The maximum observed plasma concentrations (Cmax), and the areas under the concentration-vs.-time curve until last measurable concentration (AUCt), were compared to assess bioequivalence.

Protection of trial subjects

Ethical Conduct of the Study This study was conducted in accordance with the final protocol and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines, including ICH E6. In addition, all local regulatory requirements and laws were followed. Subject Information and Consent Written informed consent was obtained before initiation of any protocol-specified activities. The investigator explained the nature, purpose, and possible risks associated with study participation to each subject. Each subject was informed that he/she could withdraw from the study at any time and for any reason. Each subject was given sufficient time to consider the implications of the study before deciding whether to participate. Subjects who chose to participate signed an informed consent document.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 Aug 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Sweden: 30

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Of 41 subjects screened for entry into the study, 30 healthy subjects were randomized to treatment. After randomization one subject withdrew his consent. Accordingly 29 subjects completed both treatments in the study.

Period 1 title

Treatment Period 1 (24 hours)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Sequence 1: Ipren followed by Brufen

Arm description

Participants received Ipren in Treatment Period 1 and Brufen in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Arm type

Experimental

Investigational medicinal product name

Ipren

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Ipren 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Investigational medicinal product name

Brufen

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brufen 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Sequence 2: Brufen followed by Ipren

Arm description

Participants received Brufen in Treatment Period 1 and Ipren in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Arm type

Experimental

Investigational medicinal product name

Ipren

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Ipren 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Investigational medicinal product name

Brufen

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brufen 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Number of subjects in period 1	Sequence 1: Ipren followed by Brufen	Sequence 2: Brufen followed by Ipren
Started	15	15
Completed	15	15

Period 2 title

Washout (48 hours)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Sequence 1: Ipren followed by Brufen

Arm description

Participants received Ipren in Treatment Period 1 and Brufen in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Arm type

Experimental

Investigational medicinal product name

Ipren

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Ipren 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Investigational medicinal product name

Brufen

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brufen 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Sequence 2: Brufen followed by Ipren

Arm description

Participants received Brufen in Treatment Period 1 and Ipren in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Arm type

Experimental

Investigational medicinal product name

Ipren

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Ipren 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Investigational medicinal product name

Brufen

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brufen 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Number of subjects in period 2	Sequence 1: Ipren followed by Brufen	Sequence 2: Brufen followed by Ipren
Started	15	15
Completed	15	14
Not completed	0	1
Consent withdrawn by subject	-	1

Period 3 title

Treatment Period 2 (24 hours)

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Sequence 1: Ipren followed by Brufen

Arm description

Participants received Ipren in Treatment Period 1 and Brufen in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Arm type

Experimental

Investigational medicinal product name

Ipren

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Ipren 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Investigational medicinal product name

Brufen

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brufen 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Sequence 2: Brufen followed by Ipren

Arm description

Participants received Brufen in Treatment Period 1 and Ipren in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Arm type

Experimental

Investigational medicinal product name

Ipren

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Ipren 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Investigational medicinal product name

Brufen

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Participants received Brufen 200 milligram (mg) tablet orally once daily on day 1 of each treatment period.

Number of subjects in period 3	Sequence 1: Ipren followed by Brufen	Sequence 2: Brufen followed by Ipren
Started	15	14
Completed	15	14

Baseline characteristics

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Reporting group title

Sequence 1: Ipren followed by Brufen

Reporting group description

Participants received Ipren in Treatment Period 1 and Brufen in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Reporting group title

Sequence 2: Brufen followed by Ipren

Reporting group description

Participants received Brufen in Treatment Period 1 and Ipren in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Reporting group values	Sequence 1: Ipren followed by Brufen	Sequence 2: Brufen followed by Ipren	Total
Number of subjects	15	15	30
Title for AgeCategorical
Units: subjects
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	15	15	30
From 65 to 84 years	0	0	0
85 years and over	0	0	0
Title for AgeContinuous
Units: years
arithmetic mean (standard deviation)	29 ( 9.47 )	27.3 ( 6.71 )	-
Title for Gender
Units: subjects
Female	5	7	12
Male	10	8	18

End points

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Reporting group title

Sequence 1: Ipren followed by Brufen

Reporting group description

Participants received Ipren in Treatment Period 1 and Brufen in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Reporting group title

Sequence 2: Brufen followed by Ipren

Reporting group description

Participants received Brufen in Treatment Period 1 and Ipren in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Reporting group title

Sequence 1: Ipren followed by Brufen

Reporting group description

Participants received Ipren in Treatment Period 1 and Brufen in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Reporting group title

Sequence 2: Brufen followed by Ipren

Reporting group description

Participants received Brufen in Treatment Period 1 and Ipren in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Reporting group title

Sequence 1: Ipren followed by Brufen

Reporting group description

Participants received Ipren in Treatment Period 1 and Brufen in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Reporting group title

Sequence 2: Brufen followed by Ipren

Reporting group description

Participants received Brufen in Treatment Period 1 and Ipren in Treatment Period 2. The washout period between the 24 hours treatment periods was at least 48 hours.

Subject analysis set title

Ipren

Subject analysis set type

Full analysis

Subject analysis set description

This study was an open, single-dose, randomized, two-way cross-over study.Thirty (30) healthy male and female volunteers, aged between 18 and 50 years, inclusive, were included. Single doses of lpren film coated tablet 200 mg and Brufen film coated tablet 200 mg were administered in a standardized mode, on two separated treatment visits. A washout period of at least 48 hours separated the treatments. After an overnight fast at the clinic, drug administration was started at about 8 am.

Subject analysis set title

Brufen

Subject analysis set type

Full analysis

Subject analysis set description

Primary: Maximal Observed Plasma Concentration (Cmax) of S-(+) Ibuprofen

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End point title

Maximal Observed Plasma Concentration (Cmax) of S-(+) Ibuprofen

End point description

The Cmax is the maximum observed plasma concentration.

End point type

Primary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: microgram(s)/millilitre (ug/mL)
arithmetic mean (standard deviation)	7.87 ( 1.83 )	9.8 ( 2.22 )

Cmax of S-(+) Ibuprofen comparison vs. Brufen

Statistical analysis description

Point and interval estimates are based on a linear model for ln-transformed Cmax data. Statistical model included covariate adjustments for period and sequence, and subject, nested within sequence as fixed effects. Number of subjects included in the cross-over analysis were 28.

Comparison groups

Ipren v Brufen

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[1]

P-value

> 0.05 ^[2]

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.233

Confidence interval

level

90%

sides

2-sided

lower limit

-0.302

upper limit

-0.164

Variability estimate

Standard error of the mean

Dispersion value

0.041

Notes
[1] - For bioequivalence the 90% CI for the treatment difference (ln-scale), Ipren vs. Brufen, had to be contained in the interval from -0.223 to 0.223.
[2] - Exact value not calculated. Inference based on 90% confidence interval.

Primary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of S-(+) Ibuprofen

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End point title

Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of S-(+) Ibuprofen

End point description

The AUCt is the area under the plasma concentration-time curve from time zero to until the last measurable plasma concentration 't'.

End point type

Primary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: microgram/milliliter x hour (ug/mL x h)
arithmetic mean (standard deviation)	37.67 ( 9.06 )	37.98 ( 10.03 )

AUCt of S-(+) Ibuprofen comparison vs. Brufen

Statistical analysis description

Point and interval estimates are based on a linear model for ln-transformed AUCt data. Statistical model included covariate adjustments for period and sequence, and subject, nested within sequence as fixed effects. Number of subjects included in the cross-over analysis were 28.

Comparison groups

Ipren v Brufen

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

equivalence ^[3]

P-value

< 0.05 ^[4]

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.018

Confidence interval

level

90%

sides

2-sided

lower limit

-0.067

upper limit

0.031

Variability estimate

Standard error of the mean

Dispersion value

0.029

Notes
[3] - For bioequivalence the 90% CI for the treatment difference (ln-scale), Ipren vs. Brufen, had to be contained in the interval from -0.223 to 0.223.
[4] - Exact value not calculated. Inference based on 90% confidence interval.

Secondary: Maximal Observed Plasma Concentration (Cmax) of R-(-) Ibuprofen and Total Ibuprofen

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End point title

Maximal Observed Plasma Concentration (Cmax) of R-(-) Ibuprofen and Total Ibuprofen

End point description

The Cmax is the maximum observed plasma concentration.

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: microgram/milliliter (ug/mL)
arithmetic mean (standard deviation)
R-(-) ibuprofen	7.97 ( 2.46 )	9.67 ( 2.27 )
Total ibuprofen	15.78 ( 4.04 )	19.36 ( 4.15 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of R-(-) Ibuprofen and Total Ibuprofen

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End point title

Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of R-(-) Ibuprofen and Total Ibuprofen

End point description

The AUCt is the area under the plasma concentration-time curve from time zero to until the last measurable plasma concentration 't'.

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: microgram/milliliter x hour (ug/mL x h)
arithmetic mean (standard deviation)
R-(-) ibuprofen	27.18 ( 7.71 )	27.77 ( 6.74 )
Total ibuprofen	65 ( 14.31 )	65.66 ( 13.95 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for S-(+) Ibuprofen

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End point title

Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for S-(+) Ibuprofen

End point description

The AUCinfinity is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: microgram/milliliter x hour (ug/mL x h)
arithmetic mean (standard deviation)	40.27 ( 10.54 )	40.12 ( 11.09 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for R-(-) Ibuprofen and Total Ibuprofen

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End point title

Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for R-(-) Ibuprofen and Total Ibuprofen

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: microgram/milliliter x hour (ug/mL x h)
arithmetic mean (standard deviation)
R-(-) ibuprofen	27.59 ( 7.75 )	28.2 ( 6.75 )
Total ibuprofen	67.66 ( 15.4 )	67.8 ( 14.82 )

No statistical analyses for this end point

Secondary: Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for S-(+) Ibuprofen

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End point title

Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for S-(+) Ibuprofen

End point description

The AUC[infinity,ex] is calculated by dividing the difference of AUC(0-infinity) and AUC(0-last) by AUC(0-infinity), (AUC[0-infinity] - AUC[0-last])/AUC[0-infinity].

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: percentage (%)
arithmetic mean (standard deviation)	6 ( 3.5 )	5.1 ( 2.8 )

No statistical analyses for this end point

Secondary: Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for R-(-) Ibuprofen and Total Ibuprofen

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End point title

Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for R-(-) Ibuprofen and Total Ibuprofen

End point description

The AUC[infinity,ex] is calculated by dividing the difference of AUC(0-infinity) and AUC(0-last) by AUC(0-infinity), (AUC[0-infinity] - AUC[0-last])/AUC[0-infinity].

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: percentage (%)
arithmetic mean (standard deviation)
R-(-) ibuprofen	1.6 ( 1 )	1.6 ( 1.1 )
Total ibuprofen	3.7 ( 2.4 )	3 ( 1.9 )

No statistical analyses for this end point

Secondary: Time at Which Maximal Plasma Concentration is Observed (Tmax) for S-(+) Ibuprofen

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End point title

Time at Which Maximal Plasma Concentration is Observed (Tmax) for S-(+) Ibuprofen

End point description

The Tmax is defined as actual sampling time to reach maximum observed S-(+) Ibuprofen concentration.

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: hours (h)
median (full range (min-max))	2.5 (1.17 to 4)	1.33 (0.83 to 4)

No statistical analyses for this end point

Secondary: Time at Which Maximal Plasma Concentration is Observed (Tmax) for R-(-) Ibuprofen and Total Ibuprofen

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End point title

Time at Which Maximal Plasma Concentration is Observed (Tmax) for R-(-) Ibuprofen and Total Ibuprofen

End point description

The Tmax is defined as actual sampling time to reach maximum observed R-(-) Ibuprofen and Total Ibuprofen concentration.

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: hours (h)
median (full range (min-max))
R-(-) ibuprofen	2.5 (1.17 to 4)	1.25 (0.83 to 4)
Total ibuprofen	2.5 (1.17 to 4)	1.25 (0.83 to 4)

No statistical analyses for this end point

Secondary: Terminal Half Life (t1/2) of S-(+) Ibuprofen

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End point title

Terminal Half Life (t1/2) of S-(+) Ibuprofen

End point description

The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: hours (h)
arithmetic mean (standard deviation)	2.47 ( 0.51 )	2.44 ( 0.36 )

No statistical analyses for this end point

Secondary: Terminal Half Life (t1/2) of R-(-) Ibuprofen and Total Ibuprofen

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End point title

Terminal Half Life (t1/2) of R-(-) Ibuprofen and Total Ibuprofen

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: hours (h)
arithmetic mean (standard deviation)
R-(-) ibuprofen	1.61 ( 0.38 )	1.6 ( 0.39 )
Total ibuprofen	2.22 ( 0.43 )	2.12 ( 0.36 )

No statistical analyses for this end point

Secondary: Mean Residence Time (MRT) for S-(+) Ibuprofen

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End point title

Mean Residence Time (MRT) for S-(+) Ibuprofen

End point description

The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as area under the first moment curve AUMC (0-infinity)/Area Under the Plasma Concentration-Time Curve AUC (0-infinity), where AUMC (0-infinity) is area under the plasma concentration-time first moment curve from time zero to infinite time and AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time.

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: hours (h)
arithmetic mean (standard deviation)	5.23 ( 0.98 )	4.58 ( 0.98 )

No statistical analyses for this end point

Secondary: Mean Residence Time (MRT) for R-(-) Ibuprofen and Total Ibuprofen

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End point title

Mean Residence Time (MRT) for R-(-) Ibuprofen and Total Ibuprofen

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: hours (h)
arithmetic mean (standard deviation)
R-(-) ibuprofen	3.66 ( 0.66 )	3.26 ( 0.72 )
Total ibuprofen	4.57 ( 0.84 )	4.01 ( 0.89 )

No statistical analyses for this end point

Secondary: Terminal Elimination Rate Constant for S-(+) Ibuprofen

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End point title

Terminal Elimination Rate Constant for S-(+) Ibuprofen

End point description

Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	29
Units: 1/hour (1/h)
arithmetic mean (standard deviation)	0.29 ( 0.07 )	0.29 ( 0.04 )

No statistical analyses for this end point

Secondary: Terminal Elimination Rate Constant for R-(-) Ibuprofen and Total Ibuprofen

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End point title

Terminal Elimination Rate Constant for R-(-) Ibuprofen and Total Ibuprofen

End point description

End point type

Secondary

End point timeframe

Pre-dose, 0.25, 0.5, 0.66, 0.83, 1, 1.16, 1.33, 1.5, 1.75, 2, 2.5, 3, 4, 5, 6, 7, 9 and 12 hours post-dose.

End point values	Ipren	Brufen
Number of subjects analysed	29	28
Units: 1/hour (1/h)
arithmetic mean (standard deviation)
R-(-) ibuprofen	0.46 ( 0.13 )	0.46 ( 0.1 )
Total ibuprofen	0.32 ( 0.07 )	0.34 ( 0.06 )

No statistical analyses for this end point

Secondary: Occurence of Adverse Events

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End point title

Occurence of Adverse Events

End point description

Serious adverse events required immediate notification within 24 hours to the sponsor or its designated representative beginning from the time that the subject provides informed consent, which was obtained prior to the subject's participation in the clinical study (i.e. prior to undergoing any study-related procedure and/or receiving investigational product), through and including 30 calendar days after the last administration of the investigational product. Any serious adverse event occurring any time after the reporting period was to be promptly reported if a causal relationship to investigational product was suspected. Adverse events (serious and non-serious) were recorded on the CRF from the time the subjects had taken at least one dose of study treatment through last subject visit.

End point type

Secondary

End point timeframe

Serious adverse events require notification within 24 hours to the sponsor or its designated representative beginning from the time that the subject provides informed consent, through and including 30 calendar days after the last administration.

End point values	Ipren	Brufen
Number of subjects analysed	29	30
Units: Number of Adverse Events
Serious adverse events	0	0
Non serious adverse events	6	11

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Serious adverse events required notification within 24 hours to the sponsor or its designated representative beginning from the time that the subject provides informed consent, through and including 30 calendar days after the last administration.

Adverse event reporting additional description

The investigator obtained and recorded on the eCRF/CRF all observed or volunteered adverse events. For all adverse events, the investigator pursued and obtained information adequate to determine both the outcome of the adverse event and whether it met the criteria for classification as a serious adverse event.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.0

Reporting group title

Brufen

Reporting group description

Ibuprofen (Brufen) Film Coated Tablet 200 mg

Reporting group title

Ipren

Reporting group description

Ibuprofen (Ipren) Film Coated Tablet 200 mg

Serious adverse events	Brufen	Ipren
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 30 (0.00%)	0 / 29 (0.00%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Brufen	Ipren
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 30 (30.00%)	6 / 29 (20.69%)
Nervous system disorders
Headache
subjects affected / exposed	7 / 30 (23.33%)	6 / 29 (20.69%)
occurrences all number	7	6
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 30 (6.67%)	0 / 29 (0.00%)
occurrences all number	2	0

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A SINGLE-DOSE, RANDOMIZED, TWO-PERIOD, CROSSOVER STUDY TO ASSESS BIOEQUIVALENCE BETWEEN TWO IBUPROFEN 200 MG TABLET FORMULATIONS, IN HEALTHY ADULTS

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Maximal Observed Plasma Concentration (Cmax) of S-(+) Ibuprofen

Primary: Maximal Observed Plasma Concentration (Cmax) of S-(+) Ibuprofen

Primary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of S-(+) Ibuprofen

Primary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of S-(+) Ibuprofen

Secondary: Maximal Observed Plasma Concentration (Cmax) of R-(-) Ibuprofen and Total Ibuprofen

Secondary: Maximal Observed Plasma Concentration (Cmax) of R-(-) Ibuprofen and Total Ibuprofen

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of R-(-) Ibuprofen and Total Ibuprofen

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Until the Time of the Last Measurable Plasma Concentration (AUCt) of R-(-) Ibuprofen and Total Ibuprofen

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for S-(+) Ibuprofen

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for S-(+) Ibuprofen

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUCinfinity) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for S-(+) Ibuprofen

Secondary: Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for S-(+) Ibuprofen

Secondary: Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Extrapolated Part of Area Under the Plasma Concentration Versus Time Curve from Start of Drug Administration Extrapolated to Infinity (AUC[infinity,ex]) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Time at Which Maximal Plasma Concentration is Observed (Tmax) for S-(+) Ibuprofen

Secondary: Time at Which Maximal Plasma Concentration is Observed (Tmax) for S-(+) Ibuprofen

Secondary: Time at Which Maximal Plasma Concentration is Observed (Tmax) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Time at Which Maximal Plasma Concentration is Observed (Tmax) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Terminal Half Life (t1/2) of S-(+) Ibuprofen

Secondary: Terminal Half Life (t1/2) of S-(+) Ibuprofen

Secondary: Terminal Half Life (t1/2) of R-(-) Ibuprofen and Total Ibuprofen

Secondary: Terminal Half Life (t1/2) of R-(-) Ibuprofen and Total Ibuprofen

Secondary: Mean Residence Time (MRT) for S-(+) Ibuprofen

Secondary: Mean Residence Time (MRT) for S-(+) Ibuprofen

Secondary: Mean Residence Time (MRT) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Mean Residence Time (MRT) for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Terminal Elimination Rate Constant for S-(+) Ibuprofen

Secondary: Terminal Elimination Rate Constant for S-(+) Ibuprofen

Secondary: Terminal Elimination Rate Constant for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Terminal Elimination Rate Constant for R-(-) Ibuprofen and Total Ibuprofen

Secondary: Occurence of Adverse Events

Secondary: Occurence of Adverse Events

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A SINGLE-DOSE, RANDOMIZED, TWO-PERIOD, CROSSOVER STUDY TO ASSESS BIOEQUIVALENCE BETWEEN TWO IBUPROFEN 200 MG TABLET FORMULATIONS, IN HEALTHY ADULTS