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Clinical Trial Results:
Placebo-controlled, double-blind evaluation of the efficacy and safety of ibuprofen 5% topical gel for the treatment of ankle sprain

Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.

Summary
EudraCT number	2015-001874-16
Trial protocol	Outside EU/EEA
Global end of trial date	19 Feb 2015

Results information
Results version number	v1(current)
This version publication date	23 Jul 2016
First version publication date	23 Jul 2016
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

B3491009

ISRCTN number

US NCT number

NCT01945034

WHO universal trial number (UTN)

Sponsor organisation name

Pfizer Inc.

Sponsor organisation address

235 E 42nd Street, New York, United States, NY 10017

Public contact

Clinical Trials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.govCallCenter@pfizer.com

Scientific contact

Clinical Trials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.govCallCenter@pfizer.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

14 Jul 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

19 Feb 2015

Was the trial ended prematurely?

Main objective of the trial

To compare the efficacy of Ibuprofen (IBU) 5 percent (%) Topical Gel versus topical placebo for the relief of pain associated with a first or second degree ankle sprain. Both twice a day (BID) and thrice a day (TID) dosing will be studied to determine the optimum dosing regimen (TID dosing vs. BID dosing).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and incompliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

08 Nov 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 304

Worldwide total number of subjects

304

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)

260

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study was conducted in United States from 08 November 2013 to 19 February 2015.

Screening details

Out of the 348 screened subjects, 304 were randomized and received treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Ibuprofen Twice Daily

Arm description

Ibuprofen 5 percent (%) topical gel twice daily was applied topically as a 4-inch strip approximately every 12 hours, for the first 7 days. Subsequently, on Days 8 through 10, subjects were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.

Arm type

Experimental

Investigational medicinal product name

Ibuprofen

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Subject received Ibuprofen 5% topical gel twice daily topically as a 4-inch strip approximately every 12 hours, for the first 7 days.

Ibuprofen Thrice Daily

Arm description

Ibuprofen 5% Topical Gel thrice a day was applied topically as a 4-inch strip approximately every 6 hours, for the first 7 days. Subsequently, on Days 8 through 10, subjects were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.

Arm type

Experimental

Investigational medicinal product name

Ibuprofen

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Subject received Ibuprofen 5% Topical Gel thrice a day topically as a 4-inch strip approximately every 6 hours, for the first 7 days.

Placebo Combined

Arm description

Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Subjects administered with Placebo matched to Ibuprofen twice daily or thrice daily regimen for the first 7 days.

Number of subjects in period 1	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Started	67	85	152
Completed	66	80	145
Not completed	1	5	7
Consent withdrawn by subject	-	3	1
Unspecified	-	1	3
Medication Error	-	1	-
Lost to follow-up	-	-	2
Protocol deviation	1	-	1

Baseline characteristics

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Reporting group title

Ibuprofen Twice Daily

Reporting group description

Reporting group title

Ibuprofen Thrice Daily

Reporting group description

Reporting group title

Placebo Combined

Reporting group description

Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.

Reporting group values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined	Total
Number of subjects	67	85	152	304
Age categorical
Units: Subjects
Adolescents (12-17 years)	16	5	18	39
Adults (18-64 years)	50	78	132	260
Elderly (From 65-84 years)	1	2	2	5
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	31.7 ± 15.2	35.2 ± 14.72	33 ± 13.9	-
Gender, Male/Female
Units: participants
Female	34	39	61	134
Male	33	46	91	170
Categorical Pain Severity Rating (PSR)
Subjects were assessed by 4-Point category pain severity rating scale. Subjects rated their pain upon weight bearing using a four-point scale, as follows: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe. All Subjects had moderate or severe ankle pain upon weight bearing at baseline.
Units: Subjects
Moderate	43	63	102	208
Severe	24	22	50	96
Baseline Subject's Global Assessment of Ankle Injury
Subjects were asked the following question: “Considering all the ways your ankle injury affects you, how are you doing today?” The subject’s response was recorded using a 5-point scale: 1 = Very Good, No symptoms and no limitations of normal activities; 2 = Good, Mild symptoms and no limitation of normal activities; 3 = Fair, Moderate symptoms and limitations of some normal activities; 4 = Poor, Severe symptoms and inability to carry out most normal activities; and 5 = Very Poor, Very severe symptoms which are intolerable and inability to carry out all normal activities.
Units: Subjects
Very Good(1)	0	0	0	0
Good(2)	0	0	7	7
Fair(3)	34	56	77	167
Poor(4)	30	25	55	110
Very Poor(5)	3	4	13	20
Baseline Physician Global Assessment of Ankle Injury
The physician assessment of the severity of the ankle injury was based on the subject’s individual signs and symptoms which included pain, swelling, tenderness and limitation of range of movement, and graded using the following 6-point scale: 0 = Normal, No signs or symptoms; 1= Very mild, Very mild signs and symptoms; 2 = Mild, Mild signs and symptoms; 3 = Moderate, Moderate signs and symptoms; 4 = Severe, Severe signs and symptoms; 5 = Very severe, Very severe signs and symptoms.
Units: Subjects
Normal(0)	0	0	0	0
Very mild(1)	0	0	1	1
Mild(2)	9	28	30	67
Moderate(3)	50	54	101	205
Severe(4)	8	3	20	31
Very severe(5)	0	0	0	0
Baseline Subject Assessment of Normal Function/Activity
Subjects were asked the following question: “How does your ankle injury affect your walking and normal activity?” The Subject’s response was recorded using a 5-point scale: 1 = Normal activity and no pain; 2 = Normal activity with pain; 3 = Mildly restricted walking due to pain and can’t resume normal activities; 4 = Moderately restricted walking due to pain and can’t resume normal activities; 5 = Severely restricted walking due to pain and can’t resume normal activities. The score ranges from 1-5, with higher scores indicates restricted activity.
Units: Subjects
Normal walking/activity and no pain(1)	0	0	0	0
Normal walking/activity with pain(2)	1	4	9	14
Mild restrict walking(3)	16	26	26	68
Moderate restrict walking(4)	43	45	91	179
Severe restrict walking(5)	7	10	26	43
Study Specific Characteristic \|
Units: Units on a scale
arithmetic mean (standard deviation)	8.3 ± 1.25	8.1 ± 1.13	8.4 ± 1.17	-
Study Specific Characteristic \|
Units: Units on a scale
arithmetic mean (standard deviation)	6.2 ± 1.77	6.5 ± 1.48	6.5 ± 1.7	-

End points

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Reporting group title

Ibuprofen Twice Daily

Reporting group description

Reporting group title

Ibuprofen Thrice Daily

Reporting group description

Reporting group title

Placebo Combined

Reporting group description

Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.

Primary: Sum of Pain Intensity Difference (SPID) on Weight Bearing Over 3 Days (SPID WB0-3)

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End point title

Sum of Pain Intensity Difference (SPID) on Weight Bearing Over 3 Days (SPID WB0-3)

End point description

PI was assessed on an 11-point numerical rating scale from 0=no pain to 10=most severe pain. Pain intensity difference (PID) was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID was calculated as the time-weighted sum of PID scores over 3 days (72 hours). Total score ranges from -360 (higher pain relief) to 432 (lower pain relief) for SPID WB0-3. SPID is a value of change from baseline and as pain score at base line is usually higher than that at post baseline, a negative value of SPID indicates higher pain relief from baseline. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Primary

End point timeframe

Over 3 Days (0-72 hours)

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: units on a scale
least squares mean (standard error)	188.9 ± 14.81	173.6 ± 13.6	165.9 ± 10.34

SPIDWB 0-3:Ibuprofen Twice DailyvsPlacebo Combined

Statistical analysis description

The analysis of variance (ANOVA) model was used which contains treatment, baseline categorical pain severity rating, pooled site blocks, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.19 ^[1]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-11.49

upper limit

57.56

Notes
[1] - p-value <=0.05 for treatment effects

SPIDWB0-3:Ibuprofen Thrice DailyvsPlacebo Combined

Statistical analysis description

The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site blocks, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.633 ^[2]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

7.8

Confidence interval

level

95%

sides

2-sided

lower limit

-24.2

upper limit

39.7

Notes
[2] - p-value <=0.05 for treatment effects

SPIDWB0-3:Ibuprofen Twice DailyvsThrice Daily

Statistical analysis description

The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site blocks, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.436 ^[3]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-15.3

Confidence interval

level

95%

sides

2-sided

lower limit

-53.87

upper limit

23.3

Notes
[3] - p-value <=0.05 for treatment effects

Primary: Sum of Ankle Pain Intensity Difference on Weight Bearing Over 24 Hours After Dose 1 (SPID WB24)

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End point title

Sum of Ankle Pain Intensity Difference on Weight Bearing Over 24 Hours After Dose 1 (SPID WB24)

End point description

PI was assessed on an 11-point numerical rating scale from 0=no pain to 10=most severe pain. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID was calculated as the time-weighted sum of PID scores over 24 hours. Total score ranges from -120 (higher pain relief) to 144 (lower pain relief) for SPID WB24. SPID is a value of change from baseline. Pain score at base line is usually higher than that at post baseline. So negative value of SPID indicates pain relief from baseline, while a positive value means a worst pain comparing to baseline, a negative value of SPID indicates higher pain relief from baseline, a negative value of SPID indicates higher pain relief from baseline. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Primary

End point timeframe

0 to 24 hours

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: units on a scale
least squares mean (standard error)	46.9 ± 5.03	41.1 ± 4.62	42.1 ± 3.51

SPIDWB24:Ibuprofen Twice DailyvsPlacebo Combined

Statistical analysis description

The ANOVA model was used which contains treatment, baseline categorical pain severity rating (BLPSR), pooled site blocks, and baseline pain intensity on weight bearing (BLPIWB) terms. 95% CI not includes 0 for treatment effect. Upper limit of 95% CI< 0 for Ibuprofen treatment significantly better than combined Placebo. Comparison: tested at the 0.05 level of significance (2-sided). A comparison was eligible for being declared significant only if preceding comparison was significant.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.426 ^[4]

Method

ANOVA

Parameter type

Least Squares (LS) Mean Difference

Point estimate

4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.98

upper limit

16.49

Notes
[4] - p-value <=0.05 for treatment effects

SPIDWB24:Ibuprofen Thrice DailyvsPlacebo Combined

Statistical analysis description

The ANOVA model was used which contains treatment, BLPSR, pooled site blocks, and BLPIWB terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo. Comparison: tested at the 0.05 level of significance (2-sided). A comparison was eligible for being declared significant only if preceding comparison was significant.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.85 ^[5]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-11.9

upper limit

9.82

Notes
[5] - p-value <=0.05 for treatment effects

SPIDWB24:Ibuprofen Twice DailyvsThrice Daily

Statistical analysis description

The ANOVA model was used which contains treatment, BLPSR, pooled site blocks, and BLPIWB terms. A comparison was eligible for being declared significant only if preceding comparison was significant.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.385 ^[6]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-18.91

upper limit

7.32

Notes
[6] - p-value <=0.05 for treatment effects

Secondary: Sum of Pain Intensity Difference at Rest Over 24 Hours on Day 1 (SPID R24)

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End point title

Sum of Pain Intensity Difference at Rest Over 24 Hours on Day 1 (SPID R24)

End point description

PI was assessed on an 11-point numerical rating scale from 0=no pain to 10=most severe pain. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID was calculated as the time-weighted sum of PID scores over 24 hours. Total score ranges from -240 (higher pain relief) to 96 (lower pain relief) for SPID at rest. SPID is a value of change from baseline. Pain score at base line is usually higher than that at post baseline. So negative value of SPID indicates pain relief from baseline, while positive value means a worst pain comparing to baseline, a negative value of SPID indicates higher pain relief from baseline. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

0 to 24 hours

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: units on a scale
least squares mean (standard error)	44.7 ± 4.65	29.4 ± 4.29	34.7 ± 3.22

SPIDR24:Ibuprofen Twice DailyvsPlacebo Combined

Statistical analysis description

The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site blocks, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.072 ^[7]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

20.91

Notes
[7] - p-value <=0.05 for treatment effects

SPIDR24:Ibuprofen Thrice DailyvsPlacebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.296 ^[8]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-5.3

Confidence interval

level

95%

sides

2-sided

lower limit

-15.4

upper limit

4.7

Notes
[8] - p-value <=0.05 for treatment effects

SPID R24: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site blocks, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014 ^[9]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-15.3

Confidence interval

level

95%

sides

2-sided

lower limit

-27.53

upper limit

-3.16

Notes
[9] - p-value <=0.05 for treatment effects

Secondary: Change From Baseline in Subject’s Global Assessment of Ankle Injury at Day 3 and 10

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End point title

Change From Baseline in Subject’s Global Assessment of Ankle Injury at Day 3 and 10

End point description

Subject’s global assessments of ankle injury was measured using 5-point scale: 1= Very Good (No symptoms and no limitations of normal activities), 2= Good (Mild symptoms and no limitation of normal activities), 3= Fair (Moderate symptoms and limitations of some normal activities), 4= Poor (Severe symptoms and inability to carry out most normal activities), 5= Very Poor (Very severe symptoms which are intolerable and inability to carry out all normal activities). The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Baseline, Day 3, 10

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: units on a scale
least squares mean (standard error)
Change at: Day 3	0.7 ± 0.09	0.7 ± 0.08	0.6 ± 0.06
Change at: Day 10	1.8 ± 0.09	1.7 ± 0.09	1.6 ± 0.07

Day 3: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject global assessment terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.305 ^[10]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.3

Notes
[10] - p-value <=0.05 for treatment effects

Day 3: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.261 ^[11]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.29

Notes
[11] - p-value <=0.05 for treatment effects

Day 3: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject global assessment terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.996 ^[12]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.22

Notes
[12] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Day 10: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject global assessment terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.21 ^[13]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.36

Notes
[13] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.556 ^[14]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.27

Notes
[14] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Day 10: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject global assessment terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.534 ^[15]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

0.17

Notes
[15] - p-value <=0.05 for treatment effects

Secondary: Change From Baseline in Physician Global Assessment of Ankle Injury at Day 3 and 10

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End point title

Change From Baseline in Physician Global Assessment of Ankle Injury at Day 3 and 10

End point description

The physician assessment of the severity of the ankle injury was based on the subject’s individual signs and symptoms which included pain, swelling, tenderness and limitation of range of movement, and was measured using 6-point scale: 0= Normal (No signs or symptoms) , 1= Very mild (Very mild signs and symptoms), 2= Mild (Mild signs and symptoms), 3= Moderate (Moderate signs and symptoms), 4= Severe (Severe signs and symptoms), 5= Very severe (Very severe signs and symptoms). A higher score is indicative of lesser improvement. Change from baseline was calculated as baseline value minus post-treatment value. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Baseline, Day 3, 10

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: units on a scale
least squares mean (standard error)
Change at: Day 3	0.7 ± 0.08	0.7 ± 0.07	0.8 ± 0.06
Change at: Day 10	1.8 ± 0.09	2 ± 0.09	2 ± 0.06

Day 3: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline physician global assessment terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.354 ^[16]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.1

Notes
[16] - p-value <=0.05 for treatment effects

Day 3: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.237 ^[17]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.07

Notes
[17] - p-value <=0.05 for treatment effects

Day 3: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline physician global assessment terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.871 ^[18]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.19

Notes
[18] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Day 10: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline physician global assessment terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.05 ^[19]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

Notes
[19] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.64 ^[20]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.15

Notes
[20] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Day 10: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline physician global assessment terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.18 ^[21]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.41

Notes
[21] - p-value <=0.05 for treatment effects

Secondary: Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points

Top of page

End point title

Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points

End point description

PI in ankle pain at rest and upon weight bearing was assessed on an 11-point numerical rating scale from 0=no pain to 10=most severe pain. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. Pain score at base line is usually higher than that at post baseline. So negative value of SPID indicates pain relief from baseline, while positive value means a worst pain comparing to baseline. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Baseline, 1, 2, 3, 4, 5, 6, 12(Day1),24(Day2),30(Day2),36(Day2),48(Day3),50(Day3),54(Day3),60(Day3),72(Day4),78(Day4),84(Day4), 96(Day5),102(Day5), 108 (Day5), 120(Day6),126(Day6),132(Day6),144(Day7),150(Day7),156(Day7) hours post first dose on Day 1

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: units on a scale
least squares mean (standard error)
Change at: At Rest 1 hour Day 1	1.3 ± 0.19	0.7 ± 0.17	1.2 ± 0.13
Change at: Upon Weight Bearing 1 hour Day 1	1.5 ± 0.2	1.1 ± 0.18	1.4 ± 0.14
Change at: At Rest 2 hour Day 1	1.7 ± 0.22	1.2 ± 0.2	1.5 ± 0.15
Change at: Upon Weight Bearing 2 hour Day 1	1.8 ± 0.23	1.5 ± 0.21	1.8 ± 0.16
Change at: At Rest 3 hour Day 1	1.9 ± 0.23	1.2 ± 0.22	1.6 ± 0.16
Change at: Upon Weight Bearing 3 hour Day 1	2.2 ± 0.25	1.7 ± 0.23	1.9 ± 0.17
Change at: At Rest 4 hour Day 1	1.8 ± 0.24	1.2 ± 0.22	1.5 ± 0.16
Change at: Upon Weight Bearing 4 hour Day 1	1.9 ± 0.25	1.8 ± 0.23	1.7 ± 0.18
Change at: At Rest 5 hour Day 1	1.9 ± 0.24	1.1 ± 0.22	1.4 ± 0.16
Upon Weight Bearing: 5 hour Day 1	2.2 ± 0.26	1.6 ± 0.24	1.7 ± 0.18
Change at: At Rest 6 hour Day 1	1.9 ± 0.24	1.1 ± 0.22	1.2 ± 0.16
Change at: Upon Weight Bearing 6 hour Day 1	2.1 ± 0.25	1.6 ± 0.23	1.5 ± 0.17
Change at: At Rest Day 1(PM)	1.8 ± 0.22	1.1 ± 0.2	1.2 ± 0.15
Change at: Upon Weight Bearing Day 1(PM)	2 ± 0.24	1.6 ± 0.22	1.6 ± 0.17
Change at: At Rest Day 2(AM)	2 ± 0.22	1.3 ± 0.2	1.6 ± 0.15
Change at: Upon Weight Bearing Day 2(AM)	2 ± 0.24	1.8 ± 0.22	1.9 ± 0.17
Change at: At Rest Day 2 Mid-day	2.3 ± 0.23	1.7 ± 0.21	1.8 ± 0.16
Change at: Upon Weight Bearing Day 2 Mid-day	2.5 ± 0.24	2.1 ± 0.22	2.1 ± 0.17
Change at: At Rest Day 2(PM)	2.2 ± 0.23	1.9 ± 0.21	1.8 ± 0.16
Change at: Upon Weight Bearing Day 2(PM)	2.4 ± 0.24	2.4 ± 0.22	2.1 ± 0.17
Change at: At Rest Day 3(AM)	2.7 ± 0.22	2 ± 0.21	2.1 ± 0.16
Change at: Upon Weight Bearing Day 3(AM)	2.8 ± 0.25	2.7 ± 0.23	2.5 ± 0.17
Change at: At Rest Day 3(AM + 2 hours)	2.8 ± 0.24	2.2 ± 0.22	2.2 ± 0.16
Change at: Upon Weight Bearing Day 3(AM + 2 hours)	2.9 ± 0.26	2.9 ± 0.24	2.6 ± 0.18
Change at: At Rest Day 3 Mid-day	3 ± 0.23	2.2 ± 0.22	2.3 ± 0.16
Change at: Upon Weight Bearing Day 3 Mid-day	3.2 ± 0.26	2.9 ± 0.24	2.7 ± 0.18
Change at: At Rest Day 3(PM)	3 ± 0.23	2.1 ± 0.22	2.3 ± 0.16
Change at: Upon Weight Bearing Day 3(PM)	3.1 ± 0.25	2.8 ± 0.23	2.7 ± 0.18
Change at: At Rest Day 4(AM)	3.2 ± 0.23	2.5 ± 0.21	2.6 ± 0.16
Change at: Upon Weight Bearing Day 4(AM)	3.4 ± 0.25	3.2 ± 0.23	3 ± 0.18
Change at: At Rest Day 4 Mid-day	3.2 ± 0.25	2.5 ± 0.23	2.5 ± 0.17
Change at: Upon Weight Bearing Day 4 Mid-day	3.5 ± 0.27	3.3 ± 0.25	3.2 ± 0.19
Change at: At Rest Day 4(PM)	3.2 ± 0.24	2.7 ± 0.22	2.5 ± 0.17
Change at: Upon Weight Bearing Day 4(PM)	3.4 ± 0.27	3.4 ± 0.25	3.1 ± 0.19
Change at: At Rest Day 5(AM)	3.3 ± 0.24	2.8 ± 0.22	2.7 ± 0.17
Change at: Upon Weight Bearing Day 5(AM)	3.7 ± 0.27	3.5 ± 0.24	3.3 ± 0.19
Change at: At Rest Day 5 Mid-day	3.4 ± 0.25	2.9 ± 0.23	2.7 ± 0.17
Change at: Upon Weight Bearing Day 5 Mid-day	3.7 ± 0.27	3.7 ± 0.25	3.3 ± 0.19
Change at: At Rest Day 5(PM)	3.4 ± 0.25	3 ± 0.23	2.8 ± 0.17
Change at: Upon Weight Bearing Day 5(PM)	3.8 ± 0.28	3.7 ± 0.26	3.5 ± 0.19
Change at: At Rest Day 6(AM)	3.5 ± 0.25	3.2 ± 0.23	3.1 ± 0.17
Change at: Upon Weight Bearing Day 6(AM)	3.9 ± 0.28	4 ± 0.26	3.8 ± 0.2
Change at: At Rest Day 6 Mid-day	3.5 ± 0.25	3.3 ± 0.23	3.1 ± 0.17
Change at: Upon Weight Bearing Day 6 Mid-day	3.8 ± 0.28	4.1 ± 0.26	3.7 ± 0.2
Change at: At Rest Day 6(PM)	3.6 ± 0.26	3.3 ± 0.24	2.9 ± 0.18
Change at: Upon Weight Bearing Day 6(PM)	3.9 ± 0.29	4.2 ± 0.27	3.7 ± 0.2
Change at: At Rest Day 7(AM)	3.6 ± 0.25	3.5 ± 0.23	3.1 ± 0.17
Change at: Upon Weight Bearing Day 7(AM)	4.2 ± 0.29	4.5 ± 0.27	3.9 ± 0.2
Change at: At Rest Day 7 Mid-day	4 ± 0.25	3.6 ± 0.23	3.2 ± 0.18
Change at: Upon Weight Bearing Day 7 Mid-day	4.6 ± 0.29	4.5 ± 0.27	4.1 ± 0.2
Change at: At Rest Day 7(PM)	3.9 ± 0.25	3.7 ± 0.23	3.4 ± 0.17
Change at: Upon Weight Bearing Day 7(PM)	4.5 ± 0.29	4.7 ± 0.27	4.2 ± 0.2

At Rest/1 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest 1 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.771 ^[22]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

0.51

Notes
[22] - p-value <=0.05 for treatment effects

At Rest/1 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022 ^[23]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

-0.07

Notes
[23] - p-value <=0.05 for treatment effects

At Rest/1 hour: Ibuprofen Twice vs Thrice Daily

Statistical analysis description

At Rest 1 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032 ^[24]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.03

upper limit

-0.05

Notes
[24] - p-value <=0.05 for treatment effects

WB/1 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing 1 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.72 ^[25]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

0.55

Notes
[25] - p-value <=0.05 for treatment effects

WB/1 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.194 ^[26]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

0.15

Notes
[26] - p-value <=0.05 for treatment effects

WB/1 hour: Ibuprofen Twice vs Thrice Daily

Statistical analysis description

Upon Weight Bearing 1 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.163 ^[27]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.89

upper limit

0.15

Notes
[27] - p-value <=0.05 for treatment effects

At Rest/2 hour:Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest 2 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.644 ^[28]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.64

Notes
[28] - p-value <=0.05 for treatment effects

At Rest/2 hour:Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.129 ^[29]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

0.11

Notes
[29] - p-value <=0.05 for treatment effects

At Rest/2 hour:Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest 2 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.096 ^[30]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.07

upper limit

0.09

Notes
[30] - p-value <=0.05 for treatment effects

WB/2 hour:Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing 2 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.905 ^[31]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.57

Notes
[31] - p-value <=0.05 for treatment effects

WB/2 hour:Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.279 ^[32]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.77

upper limit

0.22

Notes
[32] - p-value <=0.05 for treatment effects

WB/2 hour: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing 2 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.315 ^[33]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.29

Notes
[33] - p-value <=0.05 for treatment effects

At Rest/3 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest 3 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.203 ^[34]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.91

Notes
[34] - p-value <=0.05 for treatment effects

At Rest/3 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.207 ^[35]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.83

upper limit

0.18

Notes
[35] - p-value <=0.05 for treatment effects

At Rest/3 hour: Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest 3 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03 ^[36]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

-0.07

Notes
[36] - p-value <=0.05 for treatment effects

WB/3 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing 3 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.372 ^[37]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.84

Notes
[37] - p-value <=0.05 for treatment effects

WB/3 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.532 ^[38]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.36

Notes
[38] - p-value <=0.05 for treatment effects

WB/3 hour: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing 3 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.189 ^[39]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

0.21

Notes
[39] - p-value <=0.05 for treatment effects

At Rest/4 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest 4 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.264 ^[40]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.87

Notes
[40] - p-value <=0.05 for treatment effects

At Rest/4 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

At Rest 4 hour Day 1:The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.26 ^[41]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.81

upper limit

0.22

Notes
[41] - p-value <=0.05 for treatment effects

At Rest/4 hour: Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest 4 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.054 ^[42]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

0.01

Notes
[42] - p-value <=0.05 for treatment effects

WB/4 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing 4 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.456 ^[43]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

0.81

Notes
[43] - p-value <=0.05 for treatment effects

WB/4 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.639 ^[44]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.68

Notes
[44] - p-value <=0.05 for treatment effects

WB/4 hour: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing 4 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.78 ^[45]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

0.57

Notes
[45] - p-value <=0.05 for treatment effects

At Rest/5 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest 5 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.071 ^[46]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

1.07

Notes
[46] - p-value <=0.05 for treatment effects

At Rest/5 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.468 ^[47]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.32

Notes
[47] - p-value <=0.05 for treatment effects

At Rest/5 hour: Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest 5 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[48]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

-0.08

Notes
[48] - p-value <=0.05 for treatment effects

WB/5 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing 5 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.107 ^[49]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

1.09

Notes
[49] - p-value <=0.05 for treatment effects

WB/5 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.947 ^[50]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.53

Notes
[50] - p-value <=0.05 for treatment effects

WB/5 hour: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing 5 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.134 ^[51]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.18

upper limit

0.16

Notes
[51] - p-value <=0.05 for treatment effects

At Rest/6 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest 6 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.017 ^[52]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.12

upper limit

1.23

Notes
[52] - p-value <=0.05 for treatment effects

At Rest/6 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.715 ^[53]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.41

Notes
[53] - p-value <=0.05 for treatment effects

At Rest/6 hour: Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest 6 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015 ^[54]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.39

upper limit

-0.15

Notes
[54] - p-value <=0.05 for treatment effects

WB/6 hour: Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing 6 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.027 ^[55]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

1.23

Notes
[55] - p-value <=0.05 for treatment effects

WB/6 hour: Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.66 ^[56]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.42

upper limit

0.65

Notes
[56] - p-value <=0.05 for treatment effects

WB/6 hour: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing 6 hour Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.107 ^[57]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.18

upper limit

0.11

Notes
[57] - p-value <=0.05 for treatment effects

At Rest/1(PM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 1(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02 ^[58]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

1.13

Notes
[58] - p-value <=0.05 for treatment effects

At Rest/1(PM): Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.749 ^[59]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.55

upper limit

0.4

Notes
[59] - p-value <=0.05 for treatment effects

At Rest/1(PM): Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 1(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019 ^[60]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.27

upper limit

-0.12

Notes
[60] - p-value <=0.05 for treatment effects

WB/1(PM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 1(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.163 ^[61]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.96

Notes
[61] - p-value <=0.05 for treatment effects

WB/1(PM): Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.727 ^[62]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.43

upper limit

0.61

Notes
[62] - p-value <=0.05 for treatment effects

WB/1(PM): Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 1(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.336 ^[63]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.94

upper limit

0.32

Notes
[63] - p-value <=0.05 for treatment effects

At Rest/Day 2(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 2(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.174 ^[64]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.87

Notes
[64] - p-value <=0.05 for treatment effects

At Rest/Day2(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.277 ^[65]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

0.21

Notes
[65] - p-value <=0.05 for treatment effects

At Rest/Day 2(AM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 2(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.035 ^[66]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.19

upper limit

-0.04

Notes
[66] - p-value <=0.05 for treatment effects

WB/Day 2(AM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 2(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.858 ^[67]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.6

Notes
[67] - p-value <=0.05 for treatment effects

WB/Day 2(AM): Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.724 ^[68]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.42

Notes
[68] - p-value <=0.05 for treatment effects

WB/Day 2(AM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 2(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.651 ^[69]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

0.48

Notes
[69] - p-value <=0.05 for treatment effects

At Rest/Day 2(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 2 Mid-day(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.059 ^[70]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.02

upper limit

1.05

Notes
[70] - p-value <=0.05 for treatment effects

At Rest/Day 2(MD):Ibuprofen Thrice DailyvsPlacebo

Statistical analysis description

At Rest Day 2(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.766 ^[71]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.42

Notes
[71] - p-value <=0.05 for treatment effects

At Rest/Day 2(MD):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 2(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.053 ^[72]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.19

upper limit

0.01

Notes
[72] - p-value <=0.05 for treatment effects

WB/Day 2(MD): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 2(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.212 ^[73]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.92

Notes
[73] - p-value <=0.05 for treatment effects

WB/Day 2(MD): Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.911 ^[74]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.49

upper limit

0.55

Notes
[74] - p-value <=0.05 for treatment effects

WB/Day 2(MD):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 2(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.305 ^[75]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.96

upper limit

0.3

Notes
[75] - p-value <=0.05 for treatment effects

At Rest/Day 2(PM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 2(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.075 ^[76]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

1.02

Notes
[76] - p-value <=0.05 for treatment effects

At Rest/Day2(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.684 ^[77]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

0.6

Notes
[77] - p-value <=0.05 for treatment effects

At Rest/Day 2(PM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 2(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.208 ^[78]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.98

upper limit

0.21

Notes
[78] - p-value <=0.05 for treatment effects

WB/Day 2(PM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 2(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.304 ^[79]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.85

Notes
[79] - p-value <=0.05 for treatment effects

WB/Day 2(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.356 ^[80]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.76

Notes
[80] - p-value <=0.05 for treatment effects

WB/Day 2(PM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 2(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.876 ^[81]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.67

upper limit

0.58

Notes
[81] - p-value <=0.05 for treatment effects

At Rest/Day 3(AM):Ibuprofen Twice DailyvsPlacebo

Statistical analysis description

At Rest Day 3(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.02 ^[82]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

1.15

Notes
[82] - p-value <=0.05 for treatment effects

At Rest/Day 3(AM):Ibuprofen Thrice DailyvsPlacebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.94 ^[83]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

0.47

Notes
[83] - p-value <=0.05 for treatment effects

At Rest/Day 3(AM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 3(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032 ^[84]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-1.23

upper limit

-0.06

Notes
[84] - p-value <=0.05 for treatment effects

WB/Day 3(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 3(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.206 ^[85]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.95

Notes
[85] - p-value <=0.05 for treatment effects

WB/Day 3(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 3(AM):The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.31 ^[86]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.81

Notes
[86] - p-value <=0.05 for treatment effects

WB/Day 3(AM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 3(AM):The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.771 ^[87]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.74

upper limit

0.55

Notes
[87] - p-value <=0.05 for treatment effects

Rest/Day 3(AM+2h):Ibuprofen Twice DailyvsPlacebo

Statistical analysis description

At Rest Day 3(AM + 2 hours): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016 ^[88]

Method

ANOVA

Parameter type

LS Mean difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

1.24

Notes
[88] - p-value <=0.05 for treatment effects

Rest/Day3(AM+2h):Ibuprofen Thrice DailyvsPlacebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.905 ^[89]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.48

upper limit

0.54

Notes
[89] - p-value <=0.05 for treatment effects

Rest/Day 3(AM+2h):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 3(AM + 2 hours): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.039 ^[90]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.28

upper limit

-0.03

Notes
[90] - p-value <=0.05 for treatment effects

WB/Day 3(AM+2h):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 3(AM + 2 hours): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.276 ^[91]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.93

Notes
[91] - p-value <=0.05 for treatment effects

WB/Day 3(AM+2h):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.343 ^[92]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.82

Notes
[92] - p-value <=0.05 for treatment effects

WB/Day 3(AM+2h):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.849 ^[93]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

0.6

Notes
[93] - p-value <=0.05 for treatment effects

At Rest/Day 3(MD):Ibuprofen Twice DailyvsPlacebo

Statistical analysis description

At Rest Day 3(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[94]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.19

upper limit

1.29

Notes
[94] - p-value <=0.05 for treatment effects

At Rest/Day3(MD):Ibuprofen Thrice DailyvsPlacebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.763 ^[95]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.58

upper limit

0.43

Notes
[95] - p-value <=0.05 for treatment effects

At Rest/Day 3(MD):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 3(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.01 ^[96]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.43

upper limit

-0.2

Notes
[96] - p-value <=0.05 for treatment effects

WB/Day 3 (MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 3 (MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.105 ^[97]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

1.09

Notes
[97] - p-value <=0.05 for treatment effects

WB/Day 3 (MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.533 ^[98]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

0.73

Notes
[98] - p-value <=0.05 for treatment effects

WB/Day 3(MD):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 3(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.348 ^[99]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.99

upper limit

0.35

Notes
[99] - p-value <=0.05 for treatment effects

At Rest/Day 3(PM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 3(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016 ^[100]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.13

upper limit

1.23

Notes
[100] - p-value <=0.05 for treatment effects

At Rest/Day3(PM):Ibuprofen Thrice DailyvsPlacebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.483 ^[101]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

0.33

Notes
[101] - p-value <=0.05 for treatment effects

At Rest/Day 3(PM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 3(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[102]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-1.47

upper limit

-0.25

Notes
[102] - p-value <=0.05 for treatment effects

WB/Day 3(PM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 3(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.177 ^[103]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

Notes
[103] - p-value <=0.05 for treatment effects

WB/Day 3(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.586 ^[104]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.7

Notes
[104] - p-value <=0.05 for treatment effects

WB/Day 3(PM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 3(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.448 ^[105]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.41

Notes
[105] - p-value <=0.05 for treatment effects

At Rest/Day 4(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 4(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.043 ^[106]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.02

upper limit

1.09

Notes
[106] - p-value <=0.05 for treatment effects

At Rest/Day4(AM):Ibuprofen Thrice DailyvsPlacebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.688 ^[107]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.59

upper limit

0.39

Notes
[107] - p-value <=0.05 for treatment effects

At Rest/Day 4(AM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 4(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032 ^[108]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.25

upper limit

-0.06

Notes
[108] - p-value <=0.05 for treatment effects

WB/Day 4(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 4(AM):The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.179 ^[109]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.99

Notes
[109] - p-value <=0.05 for treatment effects

WB/Day 4(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 4(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.609 ^[110]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.69

Notes
[110] - p-value <=0.05 for treatment effects

WB/Day 4(AM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 4(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.435 ^[111]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.4

Notes
[111] - p-value <=0.05 for treatment effects

At Rest/Day 4(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 4(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.023 ^[112]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

1.26

Notes
[112] - p-value <=0.05 for treatment effects

At Rest/Day4(MD):Ibuprofen Thrice DailyvsPlacebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.987 ^[113]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

0.53

Notes
[113] - p-value <=0.05 for treatment effects

AtRest/Day4(MD):IbuprofenTwice DailyvsThrice Daily

Statistical analysis description

At Rest Day 4(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.04 ^[114]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.33

upper limit

-0.03

Notes
[114] - p-value <=0.05 for treatment effects

WB/Day 4(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 4(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.319 ^[115]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.31

upper limit

0.94

Notes
[115] - p-value <=0.05 for treatment effects

WB/Day 4(MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.712 ^[116]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

0.69

Notes
[116] - p-value <=0.05 for treatment effects

WB/Day 4(PM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 4(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.557 ^[117]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.91

upper limit

0.49

Notes
[117] - p-value <=0.05 for treatment effects

At Rest/Day4(PM): Ibuprofen Twice DailyvsPlacebo

Statistical analysis description

At Rest Day 4(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.015 ^[118]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.14

upper limit

1.28

Notes
[118] - p-value <=0.05 for treatment effects

At Rest/Day4(PM): Ibuprofen Twice DailyvsPlacebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.326 ^[119]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.79

Notes
[119] - p-value <=0.05 for treatment effects

At Rest/Day 4(PM): Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 4(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.167 ^[120]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.08

upper limit

0.19

Notes
[120] - p-value <=0.05 for treatment effects

WB/Day 4(PM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 4(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.35 ^[121]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

0.93

Notes
[121] - p-value <=0.05 for treatment effects

WB/Day 4(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.235 ^[122]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.93

Notes
[122] - p-value <=0.05 for treatment effects

WB/Day 4(PM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 4(PM):The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.881 ^[123]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.65

upper limit

0.76

Notes
[123] - p-value <=0.05 for treatment effects

At Rest/Day5(AM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 5(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.036 ^[124]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

1.16

Notes
[124] - p-value <=0.05 for treatment effects

At Rest/Day5(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.656 ^[125]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

0.63

Notes
[125] - p-value <=0.05 for treatment effects

At Rest/Day 5(AM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 5(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.13 ^[126]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

0.14

Notes
[126] - p-value <=0.05 for treatment effects

WB/Day 5(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 5(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.304 ^[127]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.95

Notes
[127] - p-value <=0.05 for treatment effects

WB/Day 5(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 5(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.491 ^[128]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

0.78

Notes
[128] - p-value <=0.05 for treatment effects

WB/Day 5(AM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 5(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.726 ^[129]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.82

upper limit

0.57

Notes
[129] - p-value <=0.05 for treatment effects

At Rest/Day 5(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 5(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029 ^[130]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

1.23

Notes
[130] - p-value <=0.05 for treatment effects

At Rest/Day5(MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.585 ^[131]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

0.68

Notes
[131] - p-value <=0.05 for treatment effects

At Rest/Day 5(MD):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 5(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.131 ^[132]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-1.15

upper limit

0.15

Notes
[132] - p-value <=0.05 for treatment effects

WB/Day 5(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 5(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.215 ^[133]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

1.04

Notes
[133] - p-value <=0.05 for treatment effects

WB/Day 5(MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.244 ^[134]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.94

Notes
[134] - p-value <=0.05 for treatment effects

At Rest/Day 5(PM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 5(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.067 ^[135]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

1.13

Notes
[135] - p-value <=0.05 for treatment effects

WB/Day 5(MD):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 5(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.885 ^[136]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

0.66

Notes
[136] - p-value <=0.05 for treatment effects

At Rest/Day5(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5 ^[137]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

0.73

Notes
[137] - p-value <=0.05 for treatment effects

At Rest/Day 5(PM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 5(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.276 ^[138]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.02

upper limit

0.29

Notes
[138] - p-value <=0.05 for treatment effects

WB/Day 5(PM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 5(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.413 ^[139]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

0.92

Notes
[139] - p-value <=0.05 for treatment effects

WB/Day 5(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.448 ^[140]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.37

upper limit

0.83

Notes
[140] - p-value <=0.05 for treatment effects

WB/Day 5(PM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 5(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.917 ^[141]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.76

upper limit

0.69

Notes
[141] - p-value <=0.05 for treatment effects

At Rest/Day 6(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 6(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.132 ^[142]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

1.03

Notes
[142] - p-value <=0.05 for treatment effects

At Rest/Day6(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.505 ^[143]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.35

upper limit

0.72

Notes
[143] - p-value <=0.05 for treatment effects

At Rest/Day 6(AM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 6(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.422 ^[144]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

0.38

Notes
[144] - p-value <=0.05 for treatment effects

WB/Day 6(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 6(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.386 ^[145]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.87

Notes
[145] - p-value <=0.05 for treatment effects

WB/Day 6(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.747 ^[146]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.54

upper limit

0.76

Notes
[146] - p-value <=0.05 for treatment effects

WB/Day 6(AM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 6(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.668 ^[147]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.57

upper limit

0.89

Notes
[147] - p-value <=0.05 for treatment effects

At Rest/Day 6(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 6(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.099 ^[148]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

1.08

Notes
[148] - p-value <=0.05 for treatment effects

At Rest/Day6(MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.365 ^[149]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.79

Notes
[149] - p-value <=0.05 for treatment effects

At Rest/Day 6(MD):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 6(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.463 ^[150]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

0.41

Notes
[150] - p-value <=0.05 for treatment effects

WB/Day 6(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 6(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.845 ^[151]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

0.73

Notes
[151] - p-value <=0.05 for treatment effects

WB/Day 6(MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.199 ^[152]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

1.02

Notes
[152] - p-value <=0.05 for treatment effects

WB/Day 6(MD):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 6(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.375 ^[153]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

1.08

Notes
[153] - p-value <=0.05 for treatment effects

At Rest/Day 6(PM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 6(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.028 ^[154]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.07

upper limit

1.27

Notes
[154] - p-value <=0.05 for treatment effects

At Rest/Day6(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.188 ^[155]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.92

Notes
[155] - p-value <=0.05 for treatment effects

At Rest/Day 6(PM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 6(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.375 ^[156]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.97

upper limit

0.37

Notes
[156] - p-value <=0.05 for treatment effects

WB/Day 6(PM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 6(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.552 ^[157]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

0.89

Notes
[157] - p-value <=0.05 for treatment effects

WB/Day 6(PM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.126 ^[158]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

1.12

Notes
[158] - p-value <=0.05 for treatment effects

WB/Day 6(PM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 6(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.46 ^[159]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

1.05

Notes
[159] - p-value <=0.05 for treatment effects

At Rest/Day 7(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 7(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.095 ^[160]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

1.09

Notes
[160] - p-value <=0.05 for treatment effects

At Rest/Day7(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.146 ^[161]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

0.94

Notes
[161] - p-value <=0.05 for treatment effects

At Rest/Day 7(AM):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 7(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.769 ^[162]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.75

upper limit

0.56

Notes
[162] - p-value <=0.05 for treatment effects

WB/Day 7(AM):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 7(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.405 ^[163]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.39

upper limit

0.96

Notes
[163] - p-value <=0.05 for treatment effects

WB/Day 7(AM):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.073 ^[164]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

1.2

Notes
[164] - p-value <=0.05 for treatment effects

WB/Day 7(AM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 7(AM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.458 ^[165]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

1.04

Notes
[165] - p-value <=0.05 for treatment effects

At Rest/Day 7(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 7(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[166]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.2

upper limit

1.39

Notes
[166] - p-value <=0.05 for treatment effects

At Rest/Day7(MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.209 ^[167]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.9

Notes
[167] - p-value <=0.05 for treatment effects

At Rest/Day 7(MD):Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 7(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.193 ^[168]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-1.11

upper limit

0.22

Notes
[168] - p-value <=0.05 for treatment effects

WB/Day 7(MD):Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 7(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.149 ^[169]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

1.18

Notes
[169] - p-value <=0.05 for treatment effects

WB/Day 7(MD):Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.186 ^[170]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

1.06

Notes
[170] - p-value <=0.05 for treatment effects

WB/Day 7(MD):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 7(MD): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.845 ^[171]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.84

upper limit

0.69

Notes
[171] - p-value <=0.05 for treatment effects

At Rest/Day7(PM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

At Rest Day 7(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.067 ^[172]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

1.14

Notes
[172] - p-value <=0.05 for treatment effects

At Rest/Day7(PM): Ibuprofen Thrice Dailyvs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.242 ^[173]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.87

Notes
[173] - p-value <=0.05 for treatment effects

At Rest/Day 7(PM): Ibuprofen Twice Daily vs Thrice

Statistical analysis description

At Rest Day 7(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.498 ^[174]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.88

upper limit

0.43

Notes
[174] - p-value <=0.05 for treatment effects

WB/Day 7(PM): Ibuprofen Twice Daily vs Placebo

Statistical analysis description

Upon Weight Bearing Day 7(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.33 ^[175]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

1.02

Notes
[175] - p-value <=0.05 for treatment effects

WB/Day 7(PM): Ibuprofen Thrice Daily vs Placebo

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.124 ^[176]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.14

upper limit

1.13

Notes
[176] - p-value <=0.05 for treatment effects

WB/Day 7(PM):Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Upon Weight Bearing Day 7(PM): The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.687 ^[177]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.61

upper limit

0.92

Notes
[177] - p-value <=0.05 for treatment effects

Secondary: Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3

Top of page

End point title

Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3

End point description

PI at rest and on weight bearing was assessed on an 11-point numerical rating scale from 0=no pain to 10=most severe pain. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID 0-6 was calculated as the time-weighted sum of PID scores over 6 hours on Day 1, with a total score ranges from -30 (worst) to 36 (best). SPID 0-12 was calculated as the time weighted sum of PID scores over 2 hours on Day 3, with a total score ranges from -10 (worst) to 12 (best). SPID is a value of change from baseline. Pain score at base line is usually higher than that at post baseline. So negative value of SPID indicates pain relief from baseline, while positive value means a worst pain comparing to baseline, a negative value of SPID indicates higher pain relief from baseline. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Over 6 hours on Day 1, over 2 hours on Day 3

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: units on a scale
least squares mean (standard error)
At Rest over 6 Hours on Day 1	10.4 ± 1.24	6.6 ± 1.14	8.4 ± 0.86
Weight Bearing over 6 Hours on Day 1	11.7 ± 1.31	9.4 ± 1.2	9.9 ± 0.91
At Rest over 2 Hours on Day 3	109.6 ± 9.54	79.4 ± 8.8	84.7 ± 6.6
Weight Bearing over 2 Hours on Day 3	116.1 ± 10.11	106.8 ± 9.29	102.4 ± 7.06

At Rest over 6 Hours on Day 1

Statistical analysis description

At Rest over 6 Hours on Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.166 ^[178]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.85

upper limit

4.95

Notes
[178] - p-value <=0.05 for treatment effects

At Rest over 6 Hours on Day 1

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.199 ^[179]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.42

upper limit

0.93

Notes
[179] - p-value <=0.05 for treatment effects

At Rest over 6 Hours on Day 1

Statistical analysis description

At Rest over 6 Hours on Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022 ^[180]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-3.8

Confidence interval

level

95%

sides

2-sided

lower limit

-7.04

upper limit

-0.56

Notes
[180] - p-value <=0.05 for treatment effects

Weight Bearing over 6 Hours on Day 1

Statistical analysis description

Weight Bearing over 6 Hours on Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.26 ^[181]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.3

upper limit

4.79

Notes
[181] - p-value <=0.05 for treatment effects

Weight Bearing over 6 Hours on Day 1

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.729 ^[182]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.31

upper limit

2.32

Notes
[182] - p-value <=0.05 for treatment effects

Weight Bearing over 6 Hours on Day 1

Statistical analysis description

Weight Bearing over 6 Hours on Day 1: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.196 ^[183]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-2.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.64

upper limit

1.16

Notes
[183] - p-value <=0.05 for treatment effects

At Rest over 2 Hours on Day 3

Statistical analysis description

At Rest over 2 Hours on Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.03 ^[184]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

24.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.49

upper limit

47.28

Notes
[184] - p-value <=0.05 for treatment effects

At Rest over 2 Hours on Day 3

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018 ^[185]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-30.2

Confidence interval

level

95%

sides

2-sided

lower limit

-55.24

upper limit

-5.23

Notes
[185] - p-value <=0.05 for treatment effects

At Rest over 2 Hours on Day 3

Statistical analysis description

At Rest over 2 Hours on Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.611 ^[186]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-5.3

Confidence interval

level

95%

sides

2-sided

lower limit

-25.98

upper limit

15.29

Notes
[186] - p-value <=0.05 for treatment effects

Weight Bearing over 2 Hours on Day 3

Statistical analysis description

Weight Bearing over 2 Hours on Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.251 ^[187]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

13.8

Confidence interval

level

95%

sides

2-sided

lower limit

-9.8

upper limit

37.36

Notes
[187] - p-value <=0.05 for treatment effects

Weight Bearing over 2 Hours on Day 3

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.689 ^[188]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-17.37

upper limit

26.26

Notes
[188] - p-value <=0.05 for treatment effects

Weight Bearing over 2 Hours on Day 3

Statistical analysis description

Weight Bearing over 2 Hours on Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.486 ^[189]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-9.3

Confidence interval

level

95%

sides

2-sided

lower limit

-35.69

upper limit

17.01

Notes
[189] - p-value <=0.05 for treatment effects

Secondary: Sum of Pain Intensity Difference Scores at Rest Over 3 Days

Top of page

End point title

Sum of Pain Intensity Difference Scores at Rest Over 3 Days

End point description

PI was assessed on an 11-point numerical rating scale from 0=no pain to 10=most severe pain. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID was calculated as the time-weighted sum of PID scores over 3 days (72 hours). Total score ranges from -360 (worst) to 432 (best). SPID is a value of change from baseline. Pain score at base line is usually higher than that at post baseline. So negative value of SPID indicates pain relief from baseline, while positive value means a worst pain comparing to baseline, a negative value of SPID indicates higher pain relief from baseline. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Over 3 Days (0-72 hours)

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: Units on a scale
least squares mean (standard error)	177.6 ± 13.9	131.1 ± 12.83	139 ± 9.62

Over3Days:Ibuprofen Twice DailyvsPlacebo Combined

Statistical analysis description

At Rest Over 3 Days: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021 ^[190]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

38.5

Confidence interval

level

95%

sides

2-sided

lower limit

5.9

upper limit

71.18

Notes
[190] - p-value <=0.05 for treatment effects

Over3Days:Ibuprofen Thrice DailyvsPlacebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.603 ^[191]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-7.9

Confidence interval

level

95%

sides

2-sided

lower limit

-38.02

upper limit

22.12

Notes
[191] - p-value <=0.05 for treatment effects

Over 3 Days: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

At Rest Over 3 Days: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013 ^[192]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-46.5

Confidence interval

level

95%

sides

2-sided

lower limit

-82.93

upper limit

-10.05

Notes
[192] - p-value <=0.05 for treatment effects

Secondary: Sum of Pain Intensity Difference Scores at Rest and on Weight Bearing Over 7 Days

Top of page

End point title

Sum of Pain Intensity Difference Scores at Rest and on Weight Bearing Over 7 Days

End point description

PI was assessed on an 11-point numerical rating scale from 0=no pain to 10=most severe pain. PID was the difference between baseline PI (prior to the first dose) and current PI at assessment. SPID was calculated as the time-weighted sum of PID scores over 7 days (168 hours). Total score ranges from -840 (higher pain relief) to 1008 (lower pain relief). SPID is a value of change from baseline. Pain score at base line is usually higher than that at post baseline. So negative value of SPID indicates pain relief from baseline, while positive value means a worst pain comparing to baseline, a negative value of SPID indicates higher pain relief from baseline. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Over 7 days (0-168 hours)

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: Units on a scale
least squares mean (standard error)
At Rest: Over 7 Days	472.5 ± 31.6	396.6 ± 29.16	384.8 ± 21.88
Weight Bearing: Over 7 Days	516.4 ± 34.52	507.7 ± 31.7	470.4 ± 24.09

At Rest: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

At Rest Over 7 days: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021 ^[193]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

87.7

Confidence interval

level

95%

sides

2-sided

lower limit

13.48

upper limit

161.85

Notes
[193] - p-value <=0.05 for treatment effects

At Rest:Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.735 ^[194]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

11.8

Confidence interval

level

95%

sides

2-sided

lower limit

-56.59

upper limit

80.11

Notes
[194] - p-value <=0.05 for treatment effects

At Rest: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

At Rest Over 7 days: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity at rest terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.072 ^[195]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-75.9

Confidence interval

level

95%

sides

2-sided

lower limit

-158.73

upper limit

6.93

Notes
[195] - p-value <=0.05 for treatment effects

WB: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Weight Bearing Over 7 Days: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.261 ^[196]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-34.43

upper limit

126.52

Notes
[196] - p-value <=0.05 for treatment effects

WB: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.325 ^[197]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

37.3

Confidence interval

level

95%

sides

2-sided

lower limit

-37.13

upper limit

111.8

Notes
[197] - p-value <=0.05 for treatment effects

WB: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Weight Bearing Over 7 Days: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline pain intensity on weight bearing terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.849 ^[198]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-8.7

Confidence interval

level

95%

sides

2-sided

lower limit

-98.64

upper limit

81.22

Notes
[198] - p-value <=0.05 for treatment effects

Secondary: Change From Baseline in Subject Assessment of Normal Function and Activity at Day 3 and 10

Top of page

End point title

Change From Baseline in Subject Assessment of Normal Function and Activity at Day 3 and 10

End point description

Subject assessment of normal function was measured using a 5-point scale: 1= Normal walking/activity and no pain; 2= Normal walking/activity with pain; 3= Mildly restricted walking due to pain and can’t resume normal activities; 4= Moderately restricted walking due to pain and can’t resume normal activities; 5= Severely restricted walking due to pain and can’t resume normal activities. The normal functioning and activity scores for each question range from 1 to 5, with higher scores indicating worsening of normal activity. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Baseline, Day 3, 10

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: Units on a scale
least squares mean (standard error)
Change at: Day 3	1 ± 0.1	0.9 ± 0.09	0.7 ± 0.07
Change at: Day 10	2.1 ± 0.07	2.1 ± 0.09	2.1 ± 0.09

Day 3: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject assessment of Normal Function/Activity terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.042 ^[199]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

0.49

Notes
[199] - p-value <=0.05 for treatment effects

Day 3: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.114 ^[200]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

0.4

Notes
[200] - p-value <=0.05 for treatment effects

Day 3: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Day 3: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject assessment of Normal Function/Activity terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.598 ^[201]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.2

Notes
[201] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Day 10: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject assessment of Normal Function/Activity terms. Upper limit of 95% CI < 0 for Ibuprofen treatment significantly better than combined Placebo.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.833 ^[202]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.19

Notes
[202] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.853 ^[203]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.18

upper limit

0.22

Notes
[203] - p-value <=0.05 for treatment effects

Day 10: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Day 10: The ANOVA model was used which contains treatment, baseline categorical pain severity rating, pooled site block, and baseline subject assessment of Normal Function/Activity terms.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.733 ^[204]

Method

ANOVA

Parameter type

LS Mean Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.29

Notes
[204] - p-value <=0.05 for treatment effects

Secondary: Subject’s Global Assessment of Medication at End of Study

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End point title

Subject’s Global Assessment of Medication at End of Study

End point description

Subjects Global Assessment of Medication was used to rate the medication as a pain reliever. The responses of subjects were recorded using five-point scale: 1= Very Poor, 2= Poor, 3= Fair, 4= Good, 5= Very Good. The global assessment of medication scores for each question range from 0 to 5, giving a possible score range of 0 - 5, with higher scores indicating medication as a better pain reliever. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment. Number of subjects analyzed 'N' signifies those subjects who were evaluable for the measure.

End point type

Secondary

End point timeframe

Day 10

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	62	75	141
Units: Units on a scale
arithmetic mean (standard deviation)	3.8 ± 1.18	4 ± 0.94	4 ± 1.03

No statistical analyses for this end point

Secondary: Time to First Perceptible Relief and Meaningful Relief

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End point title

Time to First Perceptible Relief and Meaningful Relief

End point description

Subjects evaluated time to first perceptible relief by stopping stopwatch labelled 'first perceptible relief' at moment subject first began to experience any relief, exact question:“Stop stopwatch when you first begin to feel any pain-relieving effect whatsoever of product”.First perceptible relief considered confirmed by meaningful relief if subject achieved both"first perceptible","meaningful" relief by either pressing second stopwatch or by indicating that his "first perceptible" relief was also"meaningful".For“time to meaningful relief,” exact question asked:“Stop stopwatch when you have meaningful relief.”Stopwatches were active up to 3 hours after dosing or until stopped by subject, or rescue medication was administered.The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment."99999" in the median and confidence interval values signifies not estimable, since median was greater than 180 min.

End point type

Secondary

End point timeframe

0 to 3 hours on Day 1

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: Minutes
median (confidence interval 95%)
First Perceptible Relief	12.9 (10.1 to 15.7)	36.4 (24.7 to 56.4)	22.7 (15.7 to 30.3)
Meaningful Relief	41.6 (31.6 to 67.5)	99999 (99999 to 99999)	72.6 (58.1 to 116.1)

FPF: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Time to First Perceptible Relief (FPF): Hazard Ratio and corresponding 95% CI were calculated based on the Wald statistic from the Proportional Hazards (PH) model with treatment, BLPSR, and pooled site blocks.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016 ^[205]

Method

Proportional Hazards Model

Parameter type

Hazard ratio (HR)

Point estimate

1.45

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

1.97

Notes
[205] - p-value <=0.05 for treatment effects

FPF: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Time to FPF: Hazard Ratio and corresponding 95% CI were calculated based on the Wald statistic from the PH model with treatment, BLPSR, and pooled site blocks.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.022 ^[206]

Method

Proportional Hazards Model

Parameter type

Hazard ratio (HR)

Point estimate

0.71

Confidence interval

level

95%

sides

2-sided

lower limit

0.53

upper limit

0.95

Notes
[206] - p-value <=0.05 for treatment effects

FPF: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Time to FPF: Hazard Ratio and corresponding 95% CI were calculated based on the Wald statistic from the PH model with treatment, BLPSR, and pooled site blocks.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[207]

Method

Proportional Hazards Model

Parameter type

Hazard ratio (HR)

Point estimate

0.49

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

0.69

Notes
[207] - p-value <=0.05 for treatment effects

MR: Ibuprofen Twice Daily vs Placebo Combined

Statistical analysis description

Time to Meaningful Relief (MR): Hazard Ratio and corresponding 95% CI were calculated based on the Wald statistic from the PH model with treatment, BLPSR, and pooled site blocks.

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[208]

Method

Proportional Hazards Model

Parameter type

Hazard ratio (HR)

Point estimate

1.79

Confidence interval

level

95%

sides

2-sided

lower limit

1.27

upper limit

2.51

Notes
[208] - p-value <=0.05 for treatment effects

MR: Ibuprofen Thrice Daily vs Placebo Combined

Statistical analysis description

Time to MR: Hazard Ratio and corresponding 95% CI were calculated based on the Wald statistic from the PH model with treatment, BLPSR, and pooled site blocks.

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[209]

Method

Proportional Hazards Model

Parameter type

Hazard ratio (HR)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

0.41

upper limit

0.88

Notes
[209] - p-value <=0.05 for treatment effects

MR: Ibuprofen Twice Daily vs Thrice Daily

Statistical analysis description

Time to MR: Hazard Ratio and corresponding 95% CI were calculated based on the Wald statistic from the PH model with treatment, BLPSR, and pooled site blocks.

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001 ^[210]

Method

Proportional Hazards Model

Parameter type

Hazard ratio (HR)

Point estimate

0.34

Confidence interval

level

95%

sides

2-sided

lower limit

0.22

upper limit

0.52

Notes
[210] - p-value <=0.05 for treatment effects

Secondary: Time to Rescue Medication After Initial Dose, and After Each Subsequent Dose

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End point title

Time to Rescue Medication After Initial Dose, and After Each Subsequent Dose

End point description

Subjects used only acetaminophen at a dose of 500 milligram (mg) every 6 hours product as needed (PRN) as rescue medication during the course of the study. Subjects who used acetaminophen were to record its use, and date and time of administration in the subject diary. Time to rescue medication after initial dose, after each subsequent dose, provided that in each dose interval at least 25% of the subjects take rescue medication was analyzed using the proportional hazard model with site, treatment group, and baseline categorical ankle pain terms in the model. Data was not analyzed since <20% subjects used rescue medication.

End point type

Secondary

End point timeframe

Post-Dose on Day 1 up to Day 10

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	0 ^[211]	0 ^[212]	0 ^[213]
Units: Minutes
arithmetic mean (standard deviation)	±	±	±

Notes
[211] - Data was not analyzed since <20% subjects used rescue medication.
[212] - Data was not analyzed since <20% subjects used rescue medication.
[213] - Data was not analyzed since <20% subjects used rescue medication.

No statistical analyses for this end point

Secondary: Number of Doses of Rescue Medication Used During the First 7 Days of Dosing

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End point title

Number of Doses of Rescue Medication Used During the First 7 Days of Dosing

End point description

Subjects received only acetaminophen 500 mg every 6 hours PRN as rescue medication during the course of the study. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Baseline up to Day 7

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: Doses
arithmetic mean (standard deviation)	1.7 ± 3.83	0.6 ± 1.41	1.2 ± 3.96

Ibuprofen Twice Daily vs Placebo Combined

Comparison groups

Ibuprofen Twice Daily v Placebo Combined

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.479 ^[214]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[214] - p-values from the Cochran-Mantel-Haenszel (CMH) test with modified ridit scores, controlling for BLPSR and site block.

Ibuprofen Thrice Daily vs Placebo Combined

Comparison groups

Ibuprofen Thrice Daily v Placebo Combined

Number of subjects included in analysis

237

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.279 ^[215]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[215] - p-values from the CMH test with modified ridit scores, controlling for BLPSR and site block.

Ibuprofen Twice Daily vs Thrice Daily

Comparison groups

Ibuprofen Twice Daily v Ibuprofen Thrice Daily

Number of subjects included in analysis

152

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.129 ^[216]

Method

Cochran-Mantel-Haenszel

Confidence interval

Notes
[216] - p-values from the CMH test with modified ridit scores, controlling for BLPSR and site block.

Secondary: Percentage of Subjects Taking Rescue Medication

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End point title

Percentage of Subjects Taking Rescue Medication

End point description

Subjects used only acetaminophen at a dose of 500 mg every 6 hours PRN as analgesia or rescue therapy during the course of the study. Subjects who used acetaminophen were to record its use, and date and time of administration in the subject diary. The full analysis set included all randomized subjects who dosed with the study medication and provided a baseline assessment.

End point type

Secondary

End point timeframe

Post first dose Day 1 up to Day 10

End point values	Ibuprofen Twice Daily	Ibuprofen Thrice Daily	Placebo Combined
Number of subjects analysed	67	85	152
Units: Percentage of subjects
number (not applicable)	28.4	18.8	25.7

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to 14 days after last study drug dose administration

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Ibuprofen Thrice Daily

Reporting group description

Reporting group title

Ibuprofen Twice Daily

Reporting group description

Reporting group title

Placebo Combined

Reporting group description

Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.

Serious adverse events	Ibuprofen Thrice Daily	Ibuprofen Twice Daily	Placebo Combined
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	0 / 152 (0.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Ibuprofen Thrice Daily	Ibuprofen Twice Daily	Placebo Combined
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 85 (5.88%)	4 / 67 (5.97%)	13 / 152 (8.55%)
Injury, poisoning and procedural complications
Arthropod bite
subjects affected / exposed	1 / 85 (1.18%)	0 / 67 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0
Contusion
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	1 / 85 (1.18%)	0 / 67 (0.00%)	4 / 152 (2.63%)
occurrences all number	1	0	4
Dizziness
subjects affected / exposed	0 / 85 (0.00%)	1 / 67 (1.49%)	0 / 152 (0.00%)
occurrences all number	0	1	0
Hypoaesthesia
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	0 / 85 (0.00%)	1 / 67 (1.49%)	1 / 152 (0.66%)
occurrences all number	0	1	1
Application site erythema
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Influenza like illness
subjects affected / exposed	0 / 85 (0.00%)	1 / 67 (1.49%)	0 / 152 (0.00%)
occurrences all number	0	1	0
Eye disorders
Eye irritation
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Dyspepsia
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Toothache
subjects affected / exposed	1 / 85 (1.18%)	0 / 67 (0.00%)	0 / 152 (0.00%)
occurrences all number	1	0	0
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	2 / 85 (2.35%)	1 / 67 (1.49%)	0 / 152 (0.00%)
occurrences all number	2	1	0
Pruritus
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Sticky skin
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Metatarsalgia
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1
Infections and infestations
Gastroenteritis
subjects affected / exposed	0 / 85 (0.00%)	0 / 67 (0.00%)	1 / 152 (0.66%)
occurrences all number	0	0	1

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: Placebo-controlled, double-blind evaluation of the efficacy and safety of ibuprofen 5% topical gel for the treatment of ankle sprain

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Sum of Pain Intensity Difference (SPID) on Weight Bearing Over 3 Days (SPID WB0-3)

Primary: Sum of Pain Intensity Difference (SPID) on Weight Bearing Over 3 Days (SPID WB0-3)

Primary: Sum of Ankle Pain Intensity Difference on Weight Bearing Over 24 Hours After Dose 1 (SPID WB24)

Primary: Sum of Ankle Pain Intensity Difference on Weight Bearing Over 24 Hours After Dose 1 (SPID WB24)

Secondary: Sum of Pain Intensity Difference at Rest Over 24 Hours on Day 1 (SPID R24)

Secondary: Sum of Pain Intensity Difference at Rest Over 24 Hours on Day 1 (SPID R24)

Secondary: Change From Baseline in Subject’s Global Assessment of Ankle Injury at Day 3 and 10

Secondary: Change From Baseline in Subject’s Global Assessment of Ankle Injury at Day 3 and 10

Secondary: Change From Baseline in Physician Global Assessment of Ankle Injury at Day 3 and 10

Secondary: Change From Baseline in Physician Global Assessment of Ankle Injury at Day 3 and 10

Secondary: Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points

Secondary: Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points

Secondary: Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3

Secondary: Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3

Secondary: Sum of Pain Intensity Difference Scores at Rest Over 3 Days

Secondary: Sum of Pain Intensity Difference Scores at Rest Over 3 Days

Secondary: Sum of Pain Intensity Difference Scores at Rest and on Weight Bearing Over 7 Days

Secondary: Sum of Pain Intensity Difference Scores at Rest and on Weight Bearing Over 7 Days

Secondary: Change From Baseline in Subject Assessment of Normal Function and Activity at Day 3 and 10

Secondary: Change From Baseline in Subject Assessment of Normal Function and Activity at Day 3 and 10

Secondary: Subject’s Global Assessment of Medication at End of Study

Secondary: Subject’s Global Assessment of Medication at End of Study

Secondary: Time to First Perceptible Relief and Meaningful Relief

Secondary: Time to First Perceptible Relief and Meaningful Relief

Secondary: Time to Rescue Medication After Initial Dose, and After Each Subsequent Dose

Secondary: Time to Rescue Medication After Initial Dose, and After Each Subsequent Dose

Secondary: Number of Doses of Rescue Medication Used During the First 7 Days of Dosing

Secondary: Number of Doses of Rescue Medication Used During the First 7 Days of Dosing

Secondary: Percentage of Subjects Taking Rescue Medication

Secondary: Percentage of Subjects Taking Rescue Medication

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Placebo-controlled, double-blind evaluation of the efficacy and safety of ibuprofen 5% topical gel for the treatment of ankle sprain