Efficacy of Topical Indomethacin Patch Over Placebo in Ankle Sprain Pain Relief

Study Overview
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Brief Summary
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This study will investigate the efficacy of the Indomethacin patch in pain relief of ankle sprain in adult patients, compared to a placebo patch

Detailed Description
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Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) which reduces pain, fever, stiffness and swelling in acute skeletal musculature injuries involving joints. However, oral Indomethacin formulations predisposes for some systemic side effects. To avoid the systemic side effects of oral Indomethacin, a topical Indomethacin formulations have been developed and approved in some countries as an Over the counter product. Present study is to investigate the efficacy of the Indomethacin patch in pain relief of ankle sprain in adult patients.

Official Title
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A Clinical Study to Assess the Efficacy of Pain Relief of Topical Indomethacin Patch Over Placebo in Ankle Sprain Patients

Conditions
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Ankle Sprain

Intervention / Treatment
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* Drug: Indomethacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant with Grade I or Grade II acute sprain of the lateral ankle within 24 hours before screening visit Participant with self-assessed pain intensity score after movement (5 steps) at the site of the ankle sprain that is >= 5 as measured on a 0-10 NRS rating. Participant with a peri-malleolar edema (sub-malleolar perimeter difference of >=20mm between injured and uninjured ankle) Exclusion Criteria: Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. Participant who had medication that could interfere with the subject's perception of pain since experiencing ankle sprain. Pregnancy , Breast Feeding and Substance Abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indomethacin patch<br>Indomethacin patch to be applied on the sprained ankle twice a day (BID). | Drug: Indomethacin<br>* Topical indomethacin<br>|
| Placebo Comparator: Placebo patch<br>Placebo patch to be applied on the sprained ankle BID. | Drug: Placebo<br>* Placebo patch<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)1-3 Days | SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0 hrs (Day 1, pre treatment), 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, 36 hrs and 48 hrs. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (time t - time t-1). Pain Intensity was assessed at baseline and at each time-point based on numerical rating scale (NRS) which is a horizontal line with a scale from 0-10, where 0 represents No and 10 represents the worst possible pain | Baseline (Day 1) to Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Relief Score (PRS) on Movement Over Time | PRS was assessed for pain on movement (walking 5 steps on flat surface) at 30, 60 minutes and 2, 4, 8 and 12 hrs after the first dose of treatment (indomethacin or placebo patch) and twice daily during the period from 12 hours to 24 hr, 36 hr, 48 hr, 60 hr, 72 hr, 84 hr, 96 hr, 108 hr, 120 hr, 132 hr and 144 hr between treatment groups. Participants were asked to choose a number on a scale of 0 to 4, where, 0- No pain relief; 1- A little or perceptible pain relief; 2- Meaningful pain relief; 3- A lot of relief; 4- Complete relief. The mean PRS scores were calculated on the basis of participant's response based on the above score. | 30 minutes (mins) to 144 hours (hrs) post treatment | 
| NRS for Pain on Movement Over Time | NRS was assessed for pain on movement (walking 5 steps on flat surface) at 30, 60 minutes and 2, 4, 8 and 12 hrs after the first dose of treatment (indomethacin or placebo patch) and twice daily during the period from 12 hours to 24 hr, 36 hr, 48 hr, 60 hr, 72 hr, 84 hr, 96 hr, 108 hr, 120 hr, 132 hr and 144 hr between treatment groups. The NRS is a horizontal line with a scale from 0-10. After application of patch (indomethacin or reference patch), patients were asked to choose a number that relates to their pain intensity on the scale of 0 to 10, where 0 represents no pain and 10 represents the worst possible pain. | 30 mins to 144 hr post treatment | 
| Change From Baseline in NRS at Rest | Mean changes in pain intensity at each time point at rest twice daily (in the morning and afternoon) from treatment day 1 to day 7 between treatment groups at time points 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 60 hrs, 72 hrs, 84 hrs, 96 hrs, 108 hrs, 120 hrs, 132 hrs and 144 hrs was measured using NRS. The NRS is a horizontal line with a scale from 0-10. After application of patch (indomethacin or reference patch), participants were asked to choose a number that relates to their pain intensity on the scale of 0 to 10, where 0 represents no pain and 10 represents the worst possible pain. | Baseline (Day 1) to Day 7 | 
| Time to Onset of Pain Relief | Time to onset of pain relief was measured by the time to reach a pain relief score of 1 (A little or perceptible pain relief). | Baseline (Day 1) to Day 3 | 
| Assessment of Sum of Pain Intensity Difference (SPID) on Movement | SPID was calculated as sum of products of Pain Intensity Differences (PID) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0 hrs (Day 1, pre treatment), 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 60 hrs, 72 hrs, 84 hrs, 96 hrs, 108 hrs, 120 hrs, 132 hrs and 144 hrs. Positive and higher scores indicate greater reduction in pain. SPIDt = ∑PID x (time t - time t-1). Pain Intensity was assessed at baseline and at each time-point based on numerical rating scale (NRS) which is a horizontal line with a scale from 0-10, where 0 represents No and 10 represents the worst possible pain. | Baseline (Day 1) to Day 7 | 
| Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | SPRID:Sum of Pain Intensity Difference (SPID) and Total Pain Relief (TOTPAR) at each post-dosing time-point. SPRID score ranged from -5.8 (least pain relief) to 40.3 (highest pain relief). SPID and TOTPAR were calculated as weighted sums of Pain Intensity Differences (PID) and Pain Relief Scores (PRS) at each measurement time; 0 hr (Day 1, pre treatment), 0.5 hr, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, 24 hr, 36 hr, 48 hr, 60 hr, 72 hr, 84 hr, 96 hr, 108 hr, 120 hr, 132 hr and 144 hr, respectively. PID was derived by subtracting the pain severity score at a given post-dosing time-point from the baseline [based on NRS which is a horizontal line with a scale from 0-10. where 0 represents No and 10 represents the worst possible pain]. NR scores were converted into PID scores by subtracting them from baseline pain scores. PRS was assessed on 5-point categorical pain relief rating scale [0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief] | Baseline (Day 1) to Day 7 | 
| Total Pain Relief (TOTPAR) on Movement | TOTPAR was calculated as sum of products of pain relief (PR) at a given time-point (t) with the time-interval from that time-point to the previous time-point (t-1). The time-intervals used were 0 hrs (Day 1, baseline), 0.5 hrs, 1 hr, 2 hrs, 4 hrs, 8 hrs, 12 hrs, 24 hrs, 36 hrs, 48 hrs, 60 hrs, 72 hrs, 84 hrs, 96 hrs, 108 hrs, 120 hrs, 132 hrs and 144 hrs. Higher score indicated greater pain relief. TOTPARt = ∑PR x (time t - time t-1). PR score was assessed at each of the above time-points based on a 5-point categorical scale [0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief]. | Baseline (Day 1) to Day 7 | 
| Patients' Global Assessment to Treatment | Patients global assessment in response to treatment was measured at the end of the study on a scale of 0 to 4 where: 0- Poor; 1- Fair; 2- Good; 3- Very Good; 4- Excellent | Baseline (Day 1) to Day 14 | 
| Rate of Rescue Medication Use | Rescue medication use was monitored throughout a period of 14 days. | Baseline (Day 1) to Day 14 | 
| Time to First Dose of Rescue Medication Use | Rescue medication use was monitored throughout a period of 14 days. | Baseline (Day 1) to Day 14 | 
| Total Dose of Rescue Medication Use | Rescue medication use was monitored throughout a period of 14 days. | Baseline (Day 1) to Day 14 |