Trial Outcomes & Findings for 5% Topical Ibuprofen (IBU) for Ankle Sprain (NCT NCT01945034)

NCT ID: NCT01945034

Last Updated: 2016-05-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

304 participants

Primary outcome timeframe

Over 3 Days (0-72 hours)

Results posted on

2016-05-26

Participant Flow

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

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

Participant milestones

Participant milestones
Measure	Ibuprofen Twice Daily 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Overall Study STARTED	67	85	152
Overall Study COMPLETED	66	80	145
Overall Study NOT COMPLETED	1	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Ibuprofen Twice Daily 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Overall Study Medication Error	0	1	0
Overall Study Withdrawal by Subject	0	3	1
Overall Study Other	0	1	3
Overall Study Lost to Follow-up	0	0	2
Overall Study Protocol Violation	1	0	1

Baseline Characteristics

5% Topical Ibuprofen (IBU) for Ankle Sprain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.	Total n=304 Participants Total of all reporting groups
Age, Continuous	31.7 years STANDARD_DEVIATION 15.20 • n=5 Participants	35.2 years STANDARD_DEVIATION 14.72 • n=7 Participants	33.0 years STANDARD_DEVIATION 13.90 • n=5 Participants	33.3 years STANDARD_DEVIATION 14.43 • n=4 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	39 Participants n=7 Participants	61 Participants n=5 Participants	134 Participants n=4 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	46 Participants n=7 Participants	91 Participants n=5 Participants	170 Participants n=4 Participants
Categorical Pain Severity Rating (PSR) Moderate	43 participants 1.25 • n=5 Participants	63 participants 1.13 • n=7 Participants	102 participants 1.17 • n=5 Participants	208 participants n=4 Participants
Categorical Pain Severity Rating (PSR) Severe	24 participants n=5 Participants	22 participants n=7 Participants	50 participants n=5 Participants	96 participants n=4 Participants
Baseline Ankle Pain upon Weight Bearing	8.3 Units on a scale STANDARD_DEVIATION 1.25 • n=5 Participants	8.1 Units on a scale STANDARD_DEVIATION 1.13 • n=7 Participants	8.4 Units on a scale STANDARD_DEVIATION 1.17 • n=5 Participants	8.3 Units on a scale STANDARD_DEVIATION 1.18 • n=4 Participants
Baseline Ankle Pain at Rest	6.2 Units on a scale STANDARD_DEVIATION 1.77 • n=5 Participants	6.5 Units on a scale STANDARD_DEVIATION 1.48 • n=7 Participants	6.5 Units on a scale STANDARD_DEVIATION 1.70 • n=5 Participants	6.4 Units on a scale STANDARD_DEVIATION 1.65 • n=4 Participants
Baseline Participant's Global Assessment of Ankle Injury Very Good(1)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Baseline Participant's Global Assessment of Ankle Injury Good(2)	0 participants n=5 Participants	0 participants n=7 Participants	7 participants n=5 Participants	7 participants n=4 Participants
Baseline Participant's Global Assessment of Ankle Injury Fair(3)	34 participants n=5 Participants	56 participants n=7 Participants	77 participants n=5 Participants	167 participants n=4 Participants
Baseline Participant's Global Assessment of Ankle Injury Poor(4)	30 participants n=5 Participants	25 participants n=7 Participants	55 participants n=5 Participants	110 participants n=4 Participants
Baseline Participant's Global Assessment of Ankle Injury Very Poor(5)	3 participants n=5 Participants	4 participants n=7 Participants	13 participants n=5 Participants	20 participants n=4 Participants
Baseline Physician Global Assessment of Ankle Injury Normal(0)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Baseline Physician Global Assessment of Ankle Injury Very mild(1)	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Baseline Physician Global Assessment of Ankle Injury Mild(2)	9 participants n=5 Participants	28 participants n=7 Participants	30 participants n=5 Participants	67 participants n=4 Participants
Baseline Physician Global Assessment of Ankle Injury Moderate(3)	50 participants n=5 Participants	54 participants n=7 Participants	101 participants n=5 Participants	205 participants n=4 Participants
Baseline Physician Global Assessment of Ankle Injury Severe(4)	8 participants n=5 Participants	3 participants n=7 Participants	20 participants n=5 Participants	31 participants n=4 Participants
Baseline Physician Global Assessment of Ankle Injury Very severe(5)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Baseline Participant Assessment of Normal Function/Activity Normal walking/activity and no pain(1)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Baseline Participant Assessment of Normal Function/Activity Normal walking/activity with pain(2)	1 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants	14 participants n=4 Participants
Baseline Participant Assessment of Normal Function/Activity Mild restrict walking(3)	16 participants n=5 Participants	26 participants n=7 Participants	26 participants n=5 Participants	68 participants n=4 Participants
Baseline Participant Assessment of Normal Function/Activity Moderate restrict walking(4)	43 participants n=5 Participants	45 participants n=7 Participants	91 participants n=5 Participants	179 participants n=4 Participants
Baseline Participant Assessment of Normal Function/Activity Severe restrict walking(5)	7 participants n=5 Participants	10 participants n=7 Participants	26 participants n=5 Participants	43 participants n=4 Participants

PRIMARY outcome

Timeframe: Over 3 Days (0-72 hours)

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Sum of Pain Intensity Difference (SPID) on Weight Bearing Over 3 Days (SPID WB0-3)	188.9 units on a scale Standard Error 14.81	173.6 units on a scale Standard Error 13.6	165.9 units on a scale Standard Error 10.34

PRIMARY outcome

Timeframe: 0 to 24 hours

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Sum of Ankle Pain Intensity Difference on Weight Bearing Over 24 Hours After Dose 1 (SPID WB24)	46.9 units on a scale Standard Error 5.03	41.1 units on a scale Standard Error 4.62	42.1 units on a scale Standard Error 3.51

SECONDARY outcome

Timeframe: 0 to 24 hours

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Sum of Pain Intensity Difference at Rest Over 24 Hours on Day 1 (SPID R24)	44.7 units on a scale Standard Error 4.65	29.4 units on a scale Standard Error 4.29	34.7 units on a scale Standard Error 3.22

SECONDARY outcome

Timeframe: Baseline, Day 3, 10

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

Participant'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).

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Change From Baseline in Participant's Global Assessment of Ankle Injury at Day 3 and 10 Change at: Day 3	0.7 units on a scale Standard Error 0.09	0.7 units on a scale Standard Error 0.08	0.6 units on a scale Standard Error 0.06
Change From Baseline in Participant's Global Assessment of Ankle Injury at Day 3 and 10 Change at: Day 10	1.8 units on a scale Standard Error 0.09	1.7 units on a scale Standard Error 0.09	1.6 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Day 3, 10

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

The physician assessment of the severity of the ankle injury was based on the participant'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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Change From Baseline in Physician Global Assessment of Ankle Injury at Day 3 and 10 Change at: Day 3	0.7 units on a scale Standard Error 0.08	0.7 units on a scale Standard Error 0.07	0.8 units on a scale Standard Error 0.06
Change From Baseline in Physician Global Assessment of Ankle Injury at Day 3 and 10 Change at: Day 10	1.8 units on a scale Standard Error 0.09	2.0 units on a scale Standard Error 0.09	2.0 units on a scale Standard Error 0.06

SECONDARY outcome

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

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

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 baseline 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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 4(PM)	3.4 units on a scale Standard Error 0.27	3.4 units on a scale Standard Error 0.25	3.1 units on a scale Standard Error 0.19
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 5(PM)	3.4 units on a scale Standard Error 0.25	3.0 units on a scale Standard Error 0.23	2.8 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 5(AM)	3.3 units on a scale Standard Error 0.24	2.8 units on a scale Standard Error 0.22	2.7 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 5(AM)	3.7 units on a scale Standard Error 0.27	3.5 units on a scale Standard Error 0.24	3.3 units on a scale Standard Error 0.19
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 5 Mid-day	3.4 units on a scale Standard Error 0.25	2.9 units on a scale Standard Error 0.23	2.7 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 5 Mid-day	3.7 units on a scale Standard Error 0.27	3.7 units on a scale Standard Error 0.25	3.3 units on a scale Standard Error 0.19
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest 1 hour Day 1	1.3 units on a scale Standard Error 0.19	0.7 units on a scale Standard Error 0.17	1.2 units on a scale Standard Error 0.13
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing 1 hour Day 1	1.5 units on a scale Standard Error 0.20	1.1 units on a scale Standard Error 0.18	1.4 units on a scale Standard Error 0.14
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest 2 hour Day 1	1.7 units on a scale Standard Error 0.22	1.2 units on a scale Standard Error 0.20	1.5 units on a scale Standard Error 0.15
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing 2 hour Day 1	1.8 units on a scale Standard Error 0.23	1.5 units on a scale Standard Error 0.21	1.8 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest 3 hour Day 1	1.9 units on a scale Standard Error 0.23	1.2 units on a scale Standard Error 0.22	1.6 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing 3 hour Day 1	2.2 units on a scale Standard Error 0.25	1.7 units on a scale Standard Error 0.23	1.9 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest 4 hour Day 1	1.8 units on a scale Standard Error 0.24	1.2 units on a scale Standard Error 0.22	1.5 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing 4 hour Day 1	1.9 units on a scale Standard Error 0.25	1.8 units on a scale Standard Error 0.23	1.7 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest 5 hour Day 1	1.9 units on a scale Standard Error 0.24	1.1 units on a scale Standard Error 0.22	1.4 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Upon Weight Bearing: 5 hour Day 1	2.2 units on a scale Standard Error 0.26	1.6 units on a scale Standard Error 0.24	1.7 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest 6 hour Day 1	1.9 units on a scale Standard Error 0.24	1.1 units on a scale Standard Error 0.22	1.2 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing 6 hour Day 1	2.1 units on a scale Standard Error 0.25	1.6 units on a scale Standard Error 0.23	1.5 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 1(PM)	1.8 units on a scale Standard Error 0.22	1.1 units on a scale Standard Error 0.20	1.2 units on a scale Standard Error 0.15
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 1(PM)	2.0 units on a scale Standard Error 0.24	1.6 units on a scale Standard Error 0.22	1.6 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 2(AM)	2.0 units on a scale Standard Error 0.22	1.3 units on a scale Standard Error 0.20	1.6 units on a scale Standard Error 0.15
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 2(AM)	2.0 units on a scale Standard Error 0.24	1.8 units on a scale Standard Error 0.22	1.9 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 2 Mid-day	2.3 units on a scale Standard Error 0.23	1.7 units on a scale Standard Error 0.21	1.8 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 2 Mid-day	2.5 units on a scale Standard Error 0.24	2.1 units on a scale Standard Error 0.22	2.1 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 2(PM)	2.2 units on a scale Standard Error 0.23	1.9 units on a scale Standard Error 0.21	1.8 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 2(PM)	2.4 units on a scale Standard Error 0.24	2.4 units on a scale Standard Error 0.22	2.1 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 3(AM)	2.7 units on a scale Standard Error 0.22	2.0 units on a scale Standard Error 0.21	2.1 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 3(AM)	2.8 units on a scale Standard Error 0.25	2.7 units on a scale Standard Error 0.23	2.5 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 3(AM + 2 hours)	2.8 units on a scale Standard Error 0.24	2.2 units on a scale Standard Error 0.22	2.2 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 3(AM + 2 hours)	2.9 units on a scale Standard Error 0.26	2.9 units on a scale Standard Error 0.24	2.6 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 3 Mid-day	3.0 units on a scale Standard Error 0.23	2.2 units on a scale Standard Error 0.22	2.3 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 3 Mid-day	3.2 units on a scale Standard Error 0.26	2.9 units on a scale Standard Error 0.24	2.7 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 3(PM)	3.0 units on a scale Standard Error 0.23	2.1 units on a scale Standard Error 0.22	2.3 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 3(PM)	3.1 units on a scale Standard Error 0.25	2.8 units on a scale Standard Error 0.23	2.7 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 4(AM)	3.2 units on a scale Standard Error 0.23	2.5 units on a scale Standard Error 0.21	2.6 units on a scale Standard Error 0.16
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 4(AM)	3.4 units on a scale Standard Error 0.25	3.2 units on a scale Standard Error 0.23	3.0 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 4 Mid-day	3.2 units on a scale Standard Error 0.25	2.5 units on a scale Standard Error 0.23	2.5 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 4 Mid-day	3.5 units on a scale Standard Error 0.27	3.3 units on a scale Standard Error 0.25	3.2 units on a scale Standard Error 0.19
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 4(PM)	3.2 units on a scale Standard Error 0.24	2.7 units on a scale Standard Error 0.22	2.5 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 5(PM)	3.8 units on a scale Standard Error 0.28	3.7 units on a scale Standard Error 0.26	3.5 units on a scale Standard Error 0.19
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 6(AM)	3.5 units on a scale Standard Error 0.25	3.2 units on a scale Standard Error 0.23	3.1 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 6(AM)	3.9 units on a scale Standard Error 0.28	4.0 units on a scale Standard Error 0.26	3.8 units on a scale Standard Error 0.20
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 6 Mid-day	3.5 units on a scale Standard Error 0.25	3.3 units on a scale Standard Error 0.23	3.1 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 6 Mid-day	3.8 units on a scale Standard Error 0.28	4.1 units on a scale Standard Error 0.26	3.7 units on a scale Standard Error 0.20
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 6(PM)	3.6 units on a scale Standard Error 0.26	3.3 units on a scale Standard Error 0.24	2.9 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 6(PM)	3.9 units on a scale Standard Error 0.29	4.2 units on a scale Standard Error 0.27	3.7 units on a scale Standard Error 0.20
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 7(AM)	3.6 units on a scale Standard Error 0.25	3.5 units on a scale Standard Error 0.23	3.1 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 7(AM)	4.2 units on a scale Standard Error 0.29	4.5 units on a scale Standard Error 0.27	3.9 units on a scale Standard Error 0.20
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 7 Mid-day	4.0 units on a scale Standard Error 0.25	3.6 units on a scale Standard Error 0.23	3.2 units on a scale Standard Error 0.18
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 7 Mid-day	4.6 units on a scale Standard Error 0.29	4.5 units on a scale Standard Error 0.27	4.1 units on a scale Standard Error 0.20
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: At Rest Day 7(PM)	3.9 units on a scale Standard Error 0.25	3.7 units on a scale Standard Error 0.23	3.4 units on a scale Standard Error 0.17
Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points Change at: Upon Weight Bearing Day 7(PM)	4.5 units on a scale Standard Error 0.29	4.7 units on a scale Standard Error 0.27	4.2 units on a scale Standard Error 0.20

SECONDARY outcome

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

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

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 (higher pain relief) to 36 (lower pain relief). 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 (higher pain relief) to 12 (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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3 At Rest over 6 Hours on Day 1	10.4 units on a scale Standard Error 1.24	6.6 units on a scale Standard Error 1.14	8.4 units on a scale Standard Error 0.86
Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3 Weight Bearing over 6 Hours on Day 1	11.7 units on a scale Standard Error 1.31	9.4 units on a scale Standard Error 1.20	9.9 units on a scale Standard Error 0.91
Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3 At Rest over 2 Hours on Day 3	109.6 units on a scale Standard Error 9.54	79.4 units on a scale Standard Error 8.80	84.7 units on a scale Standard Error 6.60
Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3 Weight Bearing over 2 Hours on Day 3	116.1 units on a scale Standard Error 10.11	106.8 units on a scale Standard Error 9.29	102.4 units on a scale Standard Error 7.06

SECONDARY outcome

Timeframe: Over 3 Days (0-72 hours)

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

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 (higher pain relief) to 432 (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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Sum of Pain Intensity Difference Scores at Rest Over 3 Days	177.6 Units on a scale Standard Error 13.90	131.1 Units on a scale Standard Error 12.83	139.0 Units on a scale Standard Error 9.62

SECONDARY outcome

Timeframe: Over 7 days (0-168 hours)

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

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 baseline 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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Sum of Pain Intensity Difference Scores at Rest and on Weight Bearing Over 7 Days At Rest: Over 7 Days	472.5 Units on a scale Standard Error 31.60	396.6 Units on a scale Standard Error 29.16	384.8 Units on a scale Standard Error 21.88
Sum of Pain Intensity Difference Scores at Rest and on Weight Bearing Over 7 Days Weight Bearing: Over 7 Days	516.4 Units on a scale Standard Error 34.52	507.7 Units on a scale Standard Error 31.70	470.4 Units on a scale Standard Error 24.09

SECONDARY outcome

Timeframe: Baseline, Day 3, 10

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

Participant 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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Change From Baseline in Participant Assessment of Normal Function and Activity at Day 3 and 10 Change at: Day 3	1.0 Units on a scale Standard Error 0.10	0.9 Units on a scale Standard Error 0.09	0.7 Units on a scale Standard Error 0.07
Change From Baseline in Participant Assessment of Normal Function and Activity at Day 3 and 10 Change at: Day 10	2.1 Units on a scale Standard Error 0.07	2.1 Units on a scale Standard Error 0.09	2.1 Units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Day 10

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment. Number of participants analyzed 'N' signifies those participants who were evaluable for the measure.

Participants Global Assessment of Medication was used to rate the medication as a pain reliever. The responses of participants were recorded using 5-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.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=62 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=75 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=141 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Participant's Global Assessment of Medication at End of Study	3.8 Units on a scale Standard Deviation 1.18	4 Units on a scale Standard Deviation 0.94	4 Units on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: 0 to 3 hours on Day 1

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

Participants evaluated time to first perceptible relief by stopping a stopwatch labelled 'first perceptible relief' at moment participant first began to experience any relief, exact question asked was: "Stop stopwatch when you first begin to feel any pain-relieving effect whatsoever of product; that is, when you first feel a little relief". First perceptible relief was considered confirmed by meaningful relief if participant achieved both "first perceptible" and "meaningful" relief by either pressing second stopwatch or by indicating that his/her "first perceptible" relief was also "meaningful". For "time to meaningful relief," exact question asked was: "Stop this stopwatch when you have meaningful relief; that is, when relief from pain is meaningful to you." Stopwatches were active up to 3 hours after dosing or until stopped by participant, or rescue medication was administered.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Time to First Perceptible Relief and Meaningful Relief First Perceptible Relief	12.9 Minutes Interval 10.1 to 15.7	36.4 Minutes Interval 24.7 to 56.4	22.7 Minutes Interval 15.7 to 30.3
Time to First Perceptible Relief and Meaningful Relief Meaningful Relief	41.6 Minutes Interval 31.6 to 67.5	NA Minutes Median and Confidence interval (CI) was not analyzed, as median was greater than 180 minutes.	72.6 Minutes Interval 58.1 to 116.1

SECONDARY outcome

Timeframe: Post-Dose on Day 1 up to Day 10

Population: Data was not analyzed since \<20% participants used rescue medication.

Participants 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. Participants who used acetaminophen were to record its use, and date and time of administration in the participant diary. Time to rescue medication after initial dose, after each subsequent dose, provided that in each dose interval at least 25% of the participants take rescue medication was analyzed using the proportional hazard model with site, treatment group, and baseline categorical ankle pain terms in the model.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Day 7

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

Participants received only acetaminophen 500 mg every 6 hours PRN as rescue medication during the course of the study.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Number of Doses of Rescue Medication Used During the First 7 Days of Dosing	1.7 Doses Standard Deviation 3.83	0.6 Doses Standard Deviation 1.41	1.2 Doses Standard Deviation 3.96

SECONDARY outcome

Timeframe: Post first dose Day 1 up to Day 10

Population: The full analysis set included all randomized participants who dosed with the study medication and provided a baseline assessment.

Participants used only acetaminophen at a dose of 500 mg every 6 hours PRN as analgesia or rescue therapy during the course of the study. Participants who used acetaminophen were to record its use, and date and time of administration in the participant diary.

Outcome measures

Outcome measures
Measure	Ibuprofen Twice Daily n=67 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 Participants 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 Participants Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Percentage of Participants Taking Rescue Medication	28.4 Percentage of participants	18.8 Percentage of participants	25.7 Percentage of participants

Adverse Events

Ibuprofen Twice Daily

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Ibuprofen Thrice Daily

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo Combined

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ibuprofen Twice Daily n=67 participants at risk 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 participants at risk 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 participants at risk Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Social circumstances Pregnancy of partner	1.5% 1/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/152 • Baseline up to 14 days after last study drug dose administration (Day 10)

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Ibuprofen Twice Daily n=67 participants at risk 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Ibuprofen Thrice Daily n=85 participants at risk 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, participants were permitted to use the study medication on an optional basis, according to the assigned dosing regimen.	Placebo Combined n=152 participants at risk Placebo matched to Ibuprofen twice daily or thrice daily regimen was applied for first 7 days.
Eye disorders Eye irritation	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Gastrointestinal disorders Constipation	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Gastrointestinal disorders Dyspepsia	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Gastrointestinal disorders Toothache	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	1.2% 1/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
General disorders Oedema peripheral	1.5% 1/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
General disorders Application site erythema	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
General disorders Influenza like illness	1.5% 1/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Infections and infestations Gastroenteritis	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	1.2% 1/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Injury, poisoning and procedural complications Contusion	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Musculoskeletal and connective tissue disorders Metatarsalgia	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Nervous system disorders Headache	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	1.2% 1/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	2.6% 4/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Nervous system disorders Dizziness	1.5% 1/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Nervous system disorders Hypoaesthesia	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Skin and subcutaneous tissue disorders Dry skin	1.5% 1/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	2.4% 2/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)
Skin and subcutaneous tissue disorders Sticky skin	0.00% 0/67 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.00% 0/85 • Baseline up to 14 days after last study drug dose administration (Day 10)	0.66% 1/152 • Baseline up to 14 days after last study drug dose administration (Day 10)