5% Topical Ibuprofen (IBU) for Ankle Sprain

Study Overview
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Brief Summary
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This study is being conducted to evaluate the effects of IBU 5% Topical Gel versus topical placebo for the relief of pain associated with a first or second degree ankle sprain. Both twice daily and three times daily regimens will be evaluated.

Official Title
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Placebo-controlled, Double-blind Evaluation Of The Efficacy And Safety Of Ibuprofen 5% Topical Gel For The Treatment Of Ankle Sprain

Conditions
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Ankle Injuries

Intervention / Treatment
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* Drug: Topical IBU twice daily
* Drug: Placebo twice daily
* Drug: Topical IBU three times daily
* Drug: Placebo three times daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First or second degree ankle sprain within 48 hours of first dose of study medication Medically cleared to participate Exclusion Criteria: Similar injury of same joint within last 6 months Requires bed rest, surgery, or over-the-counter or prescription analgesics

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Topical IBU twice daily<br> | Drug: Topical IBU twice daily<br>* Topical gel administered as 4 inch strip twice daily for 7 days, and as needed for an additional 3 days<br>|
| Placebo Comparator: Placebo twice daily<br> | Drug: Placebo twice daily<br>* Topical gel administered as a 4 inch strip twice daily for 7 days, and as needed for an additional 3 days<br>|
| Experimental: Topical IBU three times daily<br> | Drug: Topical IBU three times daily<br>* Topical gel administered as a 4 inch strip three times daily for 7 days, and as needed for additional 3 days<br>|
| Placebo Comparator: Placebo three times daily<br> | Drug: Placebo three times daily<br>* Topical gel administered as a 4 inch strip three times daily for 7 days, and as needed for additional 3 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference (SPID) on Weight Bearing Over 3 Days (SPID WB0-3) | 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. | Over 3 Days (0-72 hours) | 
| Sum of Ankle Pain Intensity Difference on Weight Bearing Over 24 Hours After Dose 1 (SPID WB24) | 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. | 0 to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Difference at Rest Over 24 Hours on Day 1 (SPID R24) | 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. | 0 to 24 hours | 
| Change From Baseline in Participant's Global Assessment of Ankle Injury at Day 3 and 10 | 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). | Baseline, Day 3, 10 | 
| Change From Baseline in Physician Global Assessment of Ankle Injury at Day 3 and 10 | 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. | Baseline, Day 3, 10 | 
| Change From Baseline in Ankle Pain at Rest and Upon Weight Bearing (PID NRS) at Pre-specified Time Points | 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. | 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 | 
| Sum of Pain Intensity Difference at Rest and on Weight Bearing Over 6 Hours on Day 1 and Over 2 Hours on Day 3 | 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. | Over 6 hours on Day 1, over 2 hours on Day 3 | 
| Sum of Pain Intensity Difference Scores at Rest Over 3 Days | 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. | Over 3 Days (0-72 hours) | 
| Sum of Pain Intensity Difference Scores at Rest and on Weight Bearing Over 7 Days | 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. | Over 7 days (0-168 hours) | 
| Change From Baseline in Participant Assessment of Normal Function and Activity at Day 3 and 10 | 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. | Baseline, Day 3, 10 | 
| Participant's Global Assessment of Medication at End of Study | 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. | Day 10 | 
| Time to First Perceptible Relief and Meaningful Relief | 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. | 0 to 3 hours on Day 1 | 
| Time to Rescue Medication After Initial Dose, and After Each Subsequent Dose | 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. | Post-Dose on Day 1 up to Day 10 | 
| Number of Doses of Rescue Medication Used During the First 7 Days of Dosing | Participants received only acetaminophen 500 mg every 6 hours PRN as rescue medication during the course of the study. | Baseline up to Day 7 | 
| Percentage of Participants Taking Rescue Medication | 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. | Post first dose Day 1 up to Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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topical ibuprofen, ankle sprain