Ankle Sprain
Conditions
Brief summary
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
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.
Interventions
DRUGIndomethacin
Topical indomethacin
DRUGPlacebo
Placebo patch
Sponsors
Rundo International Pharmaceutical Research & Development Co.,Ltd.
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sum of Pain Intensity Difference (SPID)1-3 Days | Baseline (Day 1) to Day 3 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NRS for Pain on Movement Over Time | 30 mins to 144 hr post treatment | 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. |
| Change From Baseline in NRS at Rest | Baseline (Day 1) to Day 7 | 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. |
| Time to Onset of Pain Relief | Baseline (Day 1) to Day 3 | 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). |
| Assessment of Sum of Pain Intensity Difference (SPID) on Movement | Baseline (Day 1) to Day 7 | 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. |
| Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | Baseline (Day 1) to Day 7 | 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 \[0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief\] |
| Pain Relief Score (PRS) on Movement Over Time | 30 minutes (mins) to 144 hours (hrs) post treatment | 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. |
| Patients' Global Assessment to Treatment | Baseline (Day 1) to Day 14 | 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 |
| Rate of Rescue Medication Use | Baseline (Day 1) to Day 14 | Rescue medication use was monitored throughout a period of 14 days. |
| Time to First Dose of Rescue Medication Use | Baseline (Day 1) to Day 14 | Rescue medication use was monitored throughout a period of 14 days. |
| Total Dose of Rescue Medication Use | Baseline (Day 1) to Day 14 | Rescue medication use was monitored throughout a period of 14 days. |
| Total Pain Relief (TOTPAR) on Movement | Baseline (Day 1) to Day 7 | 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 \[0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief\]. |
Countries
China
Participant flow
Recruitment details
The study was conducted across multiple sites in China.
Participants by arm
| Arm | Count |
|---|---|
| Indomethacin Patch Indomethacin patch was applied on the sprained ankle BID | 135 |
| Placebo Patch Placebo patch was applied on the sprained ankle BID | 135 |
| Total | 270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 7 | 5 |
Baseline characteristics
| Characteristic | Indomethacin Patch | Total | Placebo Patch |
|---|---|---|---|
| Age, Continuous | 37.7 Years STANDARD_DEVIATION 12.73 | 36.6 Years STANDARD_DEVIATION 12.53 | 35.6 Years STANDARD_DEVIATION 12.29 |
| Sex: Female, Male Female | 76 Participants | 149 Participants | 73 Participants |
| Sex: Female, Male Male | 59 Participants | 121 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 135 | 5 / 135 |
| serious Total, serious adverse events | 0 / 135 | 0 / 135 |
Outcome results
Primary
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
Time frame: Baseline (Day 1) to Day 3
Population: Efficacy analysis was conducted on the Intent-to-Treat (ITT) population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin Patch | Sum of Pain Intensity Difference (SPID)1-3 Days | 3.981 Score on scale | Standard Error 0.2163 |
| Placebo Patch | Sum of Pain Intensity Difference (SPID)1-3 Days | 3.264 Score on scale | Standard Error 0.2163 |
p-value: 0.020195% CI: [0.1134, 1.3199]ANCOVA
Secondary
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.
Time frame: Baseline (Day 1) to Day 7
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indomethacin Patch | Assessment of Sum of Pain Intensity Difference (SPID) on Movement | SPID (1-2 day) | 1.402 Score on scale | Standard Error 0.0985 |
| Indomethacin Patch | Assessment of Sum of Pain Intensity Difference (SPID) on Movement | SPID (1-7 day) | 17.62 Score on scale | Standard Error 0.7113 |
| Placebo Patch | Assessment of Sum of Pain Intensity Difference (SPID) on Movement | SPID (1-2 day) | 1.169 Score on scale | Standard Error 0.0985 |
| Placebo Patch | Assessment of Sum of Pain Intensity Difference (SPID) on Movement | SPID (1-7 day) | 15.82 Score on scale | Standard Error 0.7113 |
Secondary
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.
Time frame: Baseline (Day 1) to Day 7
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin Patch | Change From Baseline in NRS at Rest | -3.581 Score on scale | Standard Error 0.1273 |
| Placebo Patch | Change From Baseline in NRS at Rest | -3.194 Score on scale | Standard Error 0.1228 |
Secondary
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.
Time frame: 30 mins to 144 hr post treatment
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indomethacin Patch | NRS for Pain on Movement Over Time | 1 hr | 6.85 Score on scale | Standard Deviation 1.51 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 96 hr | 3.21 Score on scale | Standard Deviation 1.667 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 108 hr | 3.22 Score on scale | Standard Deviation 1.571 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 0.5 hr | 6.90 Score on scale | Standard Deviation 1.558 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 2 hr | 6.55 Score on scale | Standard Deviation 1.505 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 4 hr | 6.26 Score on scale | Standard Deviation 1.547 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 8 hr | 6.30 Score on scale | Standard Deviation 1.501 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 12 hr | 5.88 Score on scale | Standard Deviation 1.619 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 24 hr | 5.27 Score on scale | Standard Deviation 1.743 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 36 hr | 4.62 Score on scale | Standard Deviation 1.875 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 48 hr | 4.40 Score on scale | Standard Deviation 1.735 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 60 hr | 4.08 Score on scale | Standard Deviation 1.86 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 72 hr | 3.76 Score on scale | Standard Deviation 1.911 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 84 hr | 3.48 Score on scale | Standard Deviation 1.719 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 120 hr | 2.95 Score on scale | Standard Deviation 1.627 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 132 hr | 2.84 Score on scale | Standard Deviation 1.461 |
| Indomethacin Patch | NRS for Pain on Movement Over Time | 144 hr | 2.70 Score on scale | Standard Deviation 1.366 |
| Placebo Patch | NRS for Pain on Movement Over Time | 84 hr | 4.13 Score on scale | Standard Deviation 1.804 |
| Placebo Patch | NRS for Pain on Movement Over Time | 36 hr | 5.12 Score on scale | Standard Deviation 1.933 |
| Placebo Patch | NRS for Pain on Movement Over Time | 96 hr | 3.97 Score on scale | Standard Deviation 1.902 |
| Placebo Patch | NRS for Pain on Movement Over Time | 108 hr | 3.66 Score on scale | Standard Deviation 1.843 |
| Placebo Patch | NRS for Pain on Movement Over Time | 48 hr | 4.86 Score on scale | Standard Deviation 1.805 |
| Placebo Patch | NRS for Pain on Movement Over Time | 0.5 hr | 6.89 Score on scale | Standard Deviation 1.329 |
| Placebo Patch | NRS for Pain on Movement Over Time | 1 hr | 6.86 Score on scale | Standard Deviation 1.407 |
| Placebo Patch | NRS for Pain on Movement Over Time | 132 hr | 3.35 Score on scale | Standard Deviation 1.804 |
| Placebo Patch | NRS for Pain on Movement Over Time | 2 hr | 6.63 Score on scale | Standard Deviation 1.485 |
| Placebo Patch | NRS for Pain on Movement Over Time | 60 hr | 4.67 Score on scale | Standard Deviation 1.886 |
| Placebo Patch | NRS for Pain on Movement Over Time | 4 hr | 6.44 Score on scale | Standard Deviation 1.609 |
| Placebo Patch | NRS for Pain on Movement Over Time | 120 hr | 3.58 Score on scale | Standard Deviation 1.814 |
| Placebo Patch | NRS for Pain on Movement Over Time | 8 hr | 6.37 Score on scale | Standard Deviation 1.667 |
| Placebo Patch | NRS for Pain on Movement Over Time | 72 hr | 4.47 Score on scale | Standard Deviation 1.825 |
| Placebo Patch | NRS for Pain on Movement Over Time | 12 hr | 6.18 Score on scale | Standard Deviation 1.757 |
| Placebo Patch | NRS for Pain on Movement Over Time | 144 hr | 3.23 Score on scale | Standard Deviation 1.713 |
| Placebo Patch | NRS for Pain on Movement Over Time | 24 hr | 5.47 Score on scale | Standard Deviation 1.876 |
Secondary
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.
Time frame: 30 minutes (mins) to 144 hours (hrs) post treatment
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 1 hr | 0.40 Score on scale | Standard Deviation 0.665 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 60 hr | 2.09 Score on scale | Standard Deviation 0.965 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 12 hr | 1.22 Score on scale | Standard Deviation 0.9 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 72 hr | 2.18 Score on scale | Standard Deviation 0.934 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 4 hr | 0.80 Score on scale | Standard Deviation 0.862 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 84 hr | 2.33 Score on scale | Standard Deviation 0.886 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 24 hr | 1.64 Score on scale | Standard Deviation 0.933 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 96 hr | 2.37 Score on scale | Standard Deviation 0.92 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 2 hr | 0.58 Score on scale | Standard Deviation 0.806 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 108 hr | 2.36 Score on scale | Standard Deviation 0.856 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 36 hr | 1.93 Score on scale | Standard Deviation 0.95 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 120 hr | 2.46 Score on scale | Standard Deviation 0.954 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 8 hr | 0.84 Score on scale | Standard Deviation 0.82 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 132 hr | 2.47 Score on scale | Standard Deviation 0.928 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 48 hr | 1.94 Score on scale | Standard Deviation 0.963 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 144 hr | 2.56 Score on scale | Standard Deviation 0.895 |
| Indomethacin Patch | Pain Relief Score (PRS) on Movement Over Time | 0.5 hours | 0.24 Score on scale | Standard Deviation 0.539 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 144 hr | 2.16 Score on scale | Standard Deviation 0.982 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 0.5 hours | 0.21 Score on scale | Standard Deviation 0.546 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 1 hr | 0.42 Score on scale | Standard Deviation 0.775 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 2 hr | 0.53 Score on scale | Standard Deviation 0.791 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 4 hr | 0.68 Score on scale | Standard Deviation 0.942 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 8 hr | 0.68 Score on scale | Standard Deviation 0.861 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 12 hr | 0.94 Score on scale | Standard Deviation 1.006 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 24 hr | 1.29 Score on scale | Standard Deviation 1.055 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 36 hr | 1.55 Score on scale | Standard Deviation 1.093 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 48 hr | 1.63 Score on scale | Standard Deviation 1.006 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 60 hr | 1.65 Score on scale | Standard Deviation 0.988 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 72 hr | 1.69 Score on scale | Standard Deviation 1.006 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 84 hr | 1.84 Score on scale | Standard Deviation 0.995 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 96 hr | 1.84 Score on scale | Standard Deviation 1.018 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 108 hr | 2.07 Score on scale | Standard Deviation 0.989 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 120 hr | 1.97 Score on scale | Standard Deviation 1.026 |
| Placebo Patch | Pain Relief Score (PRS) on Movement Over Time | 132 hr | 2.14 Score on scale | Standard Deviation 1.072 |
Secondary
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
Time frame: Baseline (Day 1) to Day 14
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indomethacin Patch | Patients' Global Assessment to Treatment | 2.7 Score on scale | Standard Error 0.88 |
| Placebo Patch | Patients' Global Assessment to Treatment | 2.2 Score on scale | Standard Error 0.08 |
Secondary
Rate of Rescue Medication Use
Rescue medication use was monitored throughout a period of 14 days.
Time frame: Baseline (Day 1) to Day 14
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Indomethacin Patch | Rate of Rescue Medication Use | 4 Number of participants |
| Placebo Patch | Rate of Rescue Medication Use | 7 Number of participants |
Secondary
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 \[0-no relief, 1-little relief, 2-some relief, 3-a lot of relief, 4-complete relief\]
Time frame: Baseline (Day 1) to Day 7
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Indomethacin Patch | Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | SPRID (1-2 days) | 2.594 Score on scale | Standard Error 0.1608 |
| Indomethacin Patch | Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | SPRID (1-3 days) | 7.025 Score on scale | Standard Error 0.3409 |
| Indomethacin Patch | Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | SPRID (1-7 days) | 28.85 Score on scale | Standard Error 1.1045 |
| Placebo Patch | Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | SPRID (1-2 days) | 2.099 Score on scale | Standard Error 0.1608 |
| Placebo Patch | Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | SPRID (1-3 days) | 5.695 Score on scale | Standard Error 0.3409 |
| Placebo Patch | Sum of Pain Intensity Difference and Pain Relief (SPRID) on Movement | SPRID (1-7 days) | 25.43 Score on scale | Standard Error 1.1045 |
Secondary
Time to First Dose of Rescue Medication Use
Rescue medication use was monitored throughout a period of 14 days.
Time frame: Baseline (Day 1) to Day 14
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Indomethacin Patch | Time to First Dose of Rescue Medication Use | 0.198 Days |
| Placebo Patch | Time to First Dose of Rescue Medication Use | 0.681 Days |
Secondary
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).
Time frame: Baseline (Day 1) to Day 3
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Indomethacin Patch | Time to Onset of Pain Relief | 0.168 Days |
| Placebo Patch | Time to Onset of Pain Relief | 0.208 Days |
Secondary
Total Dose of Rescue Medication Use
Rescue medication use was monitored throughout a period of 14 days.
Time frame: Baseline (Day 1) to Day 14
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Indomethacin Patch | Total Dose of Rescue Medication Use | 3 Dose |
| Placebo Patch | Total Dose of Rescue Medication Use | 4 Dose |
Secondary
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 \[0-no relief, 1-little relief, 2-meaningful relief, 3-a lot of relief, 4-complete relief\].
Time frame: Baseline (Day 1) to Day 7
Population: Efficacy analysis was conducted on ITT population, defined as those participants who received study treatment and had at least one post-baseline efficacy measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Indomethacin Patch | Total Pain Relief (TOTPAR) on Movement | TOPTAR (1-2 days) | 1.197 Score on scale | Standard Error 0.0695 |
| Indomethacin Patch | Total Pain Relief (TOTPAR) on Movement | TOPTAR (1-3 days) | 3.057 Score on scale | Standard Error 1.389 |
| Indomethacin Patch | Total Pain Relief (TOTPAR) on Movement | TOPTAR (1-7 days) | 11.27 Score on scale | Standard Error 0.4234 |
| Placebo Patch | Total Pain Relief (TOTPAR) on Movement | TOPTAR (1-2 days) | 0.935 Score on scale | Standard Error 0.0692 |
| Placebo Patch | Total Pain Relief (TOTPAR) on Movement | TOPTAR (1-3 days) | 2.44 Score on scale | Standard Error 0.1384 |
| Placebo Patch | Total Pain Relief (TOTPAR) on Movement | TOPTAR (1-7 days) | 9.649 Score on scale | Standard Error 0.4218 |