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

This study has been completed.
Sponsor:
Collaborator:
Rundo International Pharmaceutical Research & Development Co.,Ltd.
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01957215
First received: October 4, 2013
Last updated: May 21, 2015
Last verified: April 2015
  Purpose

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


Condition Intervention Phase
Ankle Sprain
Drug: Indomethacin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Clinical Study to Assess the Efficacy of Pain Relief of Topical Indomethacin Patch Over Placebo in Ankle Sprain Patients

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Sum of Pain Intensity Difference (SPID)1-3 Days [ Time Frame: Baseline (Day 1) to Day 3 ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • Pain Relief Score (PRS) on Movement Over Time [ Time Frame: 30 minutes (mins) to 144 hours (hrs) post treatment ] [ Designated as safety issue: No ]

    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.


  • NRS for Pain on Movement Over Time [ Time Frame: 30 mins to 144 hr post treatment ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline (Day 1) to Day 7 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Day 1) to Day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Day 1) to Day 7 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline (Day 1) to Day 7 ] [ Designated as safety issue: No ]

    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]


  • Total Pain Relief (TOTPAR) on Movement [ Time Frame: Baseline (Day 1) to Day 7 ] [ Designated as safety issue: No ]

    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].


  • Patients' Global Assessment to Treatment [ Time Frame: Baseline (Day 1) to Day 14 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline (Day 1) to Day 14 ] [ Designated as safety issue: No ]
    Rescue medication use was monitored throughout a period of 14 days.

  • Time to First Dose of Rescue Medication Use [ Time Frame: Baseline (Day 1) to Day 14 ] [ Designated as safety issue: No ]
    Rescue medication use was monitored throughout a period of 14 days.

  • Total Dose of Rescue Medication Use [ Time Frame: Baseline (Day 1) to Day 14 ] [ Designated as safety issue: No ]
    Rescue medication use was monitored throughout a period of 14 days.


Enrollment: 270
Study Start Date: October 2013
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indomethacin patch
Indomethacin patch to be applied on the sprained ankle twice a day (BID).
Drug: Indomethacin
Topical indomethacin
Placebo Comparator: Placebo patch
Placebo patch to be applied on the sprained ankle BID.
Drug: Placebo
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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01957215

Locations
China, Jiangsu
Changzhou NO.2 People's Hospital
Changzhou, Jiangsu, China, 213003
Changzhou NO.2 People?s Hospital
Changzhou, Jiangsu, China, 213003
Zhongda Hospital Southeast University
Nanjing, Jiangsu, China, 210009
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China, 215006
China, Shanghai
Shanghai First People?s Hospital
Shanghai, Shanghai, China, 201620
Shanghai East Hospital
Shanghai, Shanghai, China, 200120
Shanghai First People's Hospital
Shanghai, Shanghai, China, 201620
Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai, China, 200092
Shanghai First Peoples Hospital
Shanghai, Shanghai, China, 201620
Shanghai Ruijin Hospital
Shanghai, Shanghai, China, 200025
Shanghai Tenth People's Hospital
Shanghai, Shanghai, China, 200072
Shanghai Tenth People?s Hospital
Shanghai, Shanghai, China, 200072
Shanghai Tenth Peoples Hospital
Shanghai, Shanghai, China, 200072
Shanghai Xuhui Centre Hospital
Shanghai, Shanghai, China, 200031
Ruijin Hospital Luwan Branch
Shanghai, Shanghai, China, 200020
Sponsors and Collaborators
GlaxoSmithKline
Rundo International Pharmaceutical Research & Development Co.,Ltd.
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01957215     History of Changes
Other Study ID Numbers: 202177, RH01778
Study First Received: October 4, 2013
Results First Received: March 26, 2015
Last Updated: May 21, 2015
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Ankle Injuries
Leg Injuries
Wounds and Injuries
Indomethacin
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Gout Suppressants
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Sensory System Agents
Therapeutic Uses
Tocolytic Agents

ClinicalTrials.gov processed this record on August 31, 2015