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

Ankle Sprain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01957215
• Other study ID #: 202177
• Secondary ID: RH01778
• Status: Completed
• Phase: Phase 4
• First received: October 4, 2013
• Last updated: May 21, 2015
• Start date: October 2013
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ankle Injuries
• Ankle Sprain

Intervention

Drug:
• Indomethacin
Topical indomethacin
• Placebo
Placebo patch

Locations

Country	Name	City	State
China	Changzhou NO.2 People's Hospital	Changzhou	Jiangsu
China	Changzhou NO.2 People?s Hospital	Changzhou	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	Ruijin Hospital Luwan Branch	Shanghai	Shanghai
China	Shanghai East Hospital	Shanghai	Shanghai
China	Shanghai First People's Hospital	Shanghai	Shanghai
China	Shanghai First People?s Hospital	Shanghai	Shanghai
China	Shanghai First Peoples Hospital	Shanghai	Shanghai
China	Shanghai Ruijin Hospital	Shanghai	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai	Shanghai
China	Shanghai Tenth People?s Hospital	Shanghai	Shanghai
China	Shanghai Tenth Peoples Hospital	Shanghai	Shanghai
China	Shanghai Xuhui Centre Hospital	Shanghai	Shanghai
China	Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	Rundo International Pharmaceutical Research & Development Co.,Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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"	Baseline (Day 1) to Day 3	No
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.	30 minutes (mins) to 144 hours (hrs) post treatment	No
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.	30 mins to 144 hr post treatment	No
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.	Baseline (Day 1) to Day 7	No
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").	Baseline (Day 1) to Day 3	No
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".	Baseline (Day 1) to Day 7	No
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]	Baseline (Day 1) to Day 7	No
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].	Baseline (Day 1) to Day 7	No
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	Baseline (Day 1) to Day 14	No
Secondary	Rate of Rescue Medication Use	Rescue medication use was monitored throughout a period of 14 days.	Baseline (Day 1) to Day 14	No
Secondary	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	No
Secondary	Total Dose of Rescue Medication Use	Rescue medication use was monitored throughout a period of 14 days.	Baseline (Day 1) to Day 14	No