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A Multicenter Efficacy Study of a Diclofenac+Menthol Gel in Subjects With Ankle Sprain

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ClinicalTrials.gov Identifier: NCT02100670
Recruitment Status : Completed
First Posted : April 1, 2014
Results First Posted : January 12, 2018
Last Update Posted : January 12, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pain
Interventions Drug: 1% diclofenac sodium plus 3% menthol
Drug: 1% diclofenac sodium plus 0.09% menthol
Drug: 3% menthol
Drug: Placebo with 0.09% menthol gel
Enrollment 385
Recruitment Details Participants were recruited at 16 centers in Germany.
Pre-assignment Details A total of 388 participants were screened, out of which 385 were randomized, 3 did not meet the study criteria. Of the 385 participants randomized, 360 participants completed the study, 25 did not complete the study.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description 1% diclofenac sodium with 3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. 1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. 3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Period Title: Overall Study
Started 118 113 78 76
Completed 105 106 74 75
Not Completed 13 7 4 1
Reason Not Completed
Adverse Event             10             3             3             0
Lost to Follow-up             1             0             0             0
Protocol Violation             0             1             0             1
Withdrawal of Consent             0             1             1             0
No swelling no pain             1             0             0             0
Poor Efficacy             0             1             0             0
Physician Decision             0             1             0             0
Withdrawal by Subject             1             0             0             0
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo Total
Hide Arm/Group Description 1% diclofenac sodium with 3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. 1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. 3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. Total of all reporting groups
Overall Number of Baseline Participants 117 112 77 75 381
Hide Baseline Analysis Population Description
Only 381 participants were included in safety population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 117 participants 112 participants 77 participants 75 participants 381 participants
32.4  (11.83) 32.1  (11.40) 33.8  (12.15) 33.2  (11.63) 32.8  (11.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 117 participants 112 participants 77 participants 75 participants 381 participants
Female
50
  42.7%
41
  36.6%
39
  50.6%
35
  46.7%
165
  43.3%
Male
67
  57.3%
71
  63.4%
38
  49.4%
40
  53.3%
216
  56.7%
1.Primary Outcome
Title Area Under the Curve From Day 1 to Day 3 (AUC1-3 Days) of Pain Intensity(PI) on Movement for Diclofenac/Methanol Gel and Placebo Gel
Hide Description AUC of PI on movement was measured by a numerical rating scale (NRS) during the 48 hour time interval from Day 1 to 3. AUC1-3 day was calculated based on trapezoidal method. Pain intensity was measured in NRS scale from 0 (no pain) to 10 (extreme pain). Participants assessed the severity of ankle pain using the NRS scale at baseline (prior to treatment) and at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing.
Time Frame up to 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium Plus (+) 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo gel was supplied in 30g tubes for each participant to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 75
Mean (Standard Deviation)
Unit of Measure: NRS Score (0 – 10 scale) * hrs
276.97  (111.356) 282.88  (100.958)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium Plus (+) 3% Menthol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4144
Comments P-value from multiple comparisons using t-test in Proc Mixed
Method ANCOVA
Comments Least squares (LS) means from mixed model analysis of covariance with treatment, site as fixed effects, pain intensity at baseline as a covariates.
Method of Estimation Estimation Parameter Difference of LS mean
Estimated Value -9.23
Confidence Interval (2-Sided) 95%
-31.45 to 12.98
Estimation Comments Difference of LS mean of first named treatment minus second named treatment. Lower values of LS mean favours a better response because of lower pain intensity over time. 95% Confidence intervals of difference between LS means.
2.Secondary Outcome
Title AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo
Hide Description AUC of PI on movement was measured by a numerical rating scale (NRS) during the 48 hour time interval from Day 1 to 3. AUC1-3 day was calculated based on trapezoidal method. Pain intensity was measured in NRS scale from 0 (no pain) to 10 (extreme pain). Participants assessed the severity of ankle pain using the NRS scale at baseline (prior to treatment) and at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing.
Time Frame up to 72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Mean (Standard Deviation)
Unit of Measure: NRS Score (0 – 10 scale) * hrs
276.97  (111.356) 261.11  (96.791) 272.65  (118.196) 282.88  (100.958)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 1% Diclofenac Sodium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8761
Comments P-value from multiple comparisons using t-test in Proc Mixed
Method ANCOVA
Comments Least squares (LS) means from mixed model analysis of covariance with treatment, site as fixed effects, pain intensity at baseline as a covariates.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
-18.34 to 21.50
Estimation Comments Difference of LS mean of first named treatment minus second named treatment. Lower values of LS mean favours a better response because of lower pain intensity over time. 95% Confidence intervals of difference between LS means.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 3% Menthol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8164
Comments P-value from multiple comparisons using t-test in Proc Mixed
Method ANCOVA
Comments Least squares (LS) means from mixed model analysis of covariance with treatment, site as fixed effects, pain intensity at baseline as a covariates.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 2.61
Confidence Interval (2-Sided) 95%
-19.46 to 24.67
Estimation Comments Difference of LS mean of first named treatment minus second named treatment. Lower values of LS mean favours a better response because of lower pain intensity over time. 95% Confidence intervals of difference between LS means.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium, 3% Menthol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9279
Comments P-value from multiple comparisons using t-test in Proc Mixed
Method ANCOVA
Comments Least squares (LS) means from mixed model analysis of covariance with treatment, site as fixed effects, pain intensity at baseline as a covariates.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
-21.27 to 23.33
Estimation Comments Difference of LS mean of first named treatment minus second named treatment. Lower values of LS mean favours a better response because of lower pain intensity over time. 95% Confidence intervals of difference between LS means.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3442
Comments P-value from multiple comparisons using t-test in Proc Mixed.
Method ANCOVA
Comments Least squares (LS) means from mixed model analysis of covariance with treatment, site as fixed effects, pain intensity at baseline as a covariates.
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -10.81
Confidence Interval (2-Sided) 95%
-33.26 to 11.64
Estimation Comments Difference of LS mean of first named treatment minus second named treatment. Lower values of LS mean favours a better response because of lower pain intensity over time. 95% Confidence intervals of difference between LS means.
3.Secondary Outcome
Title Pain Intensity Difference (PID) on Movement
Hide Description

PID on movement, calculated as PI at a given time 't' (after walking 5 steps on a flat surface) subtracted by the PI at baseline.

Participants assessed the severity of ankle pain (PI) using the NRS scale from 0 (no pain) to 10 (extreme pain). PI was measured at baseline (prior to treatment) and at 10, 30 minutes (min.) and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing.

Time Frame Baseline to 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population. n is number of participants analyzed for respective time point for this outcome.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Mean (Standard Deviation)
Unit of Measure: score on scale
PI at Baseline (n=117, 112, 77, 75) 7.8  (1.55) 7.4  (1.44) 7.8  (1.60) 7.7  (1.47)
PID at 10 min. (n=117, 112, 77, 75) 0.23  (1.078) 0.19  (0.855) 0.29  (0.886) 0.32  (1.129)
PID at 30 min. (n=117, 112, 77, 75) 0.44  (1.302) 0.36  (0.967) 0.49  (0.868) 0.55  (1.464)
PID at 1 hour (n=117, 112, 77, 75) 0.56  (1.348) 0.50  (1.022) 0.64  (1.146) 0.64  (1.521)
PID at 4 hour (n=117, 112, 77, 75) 0.71  (1.640) 0.48  (1.057) 0.79  (1.128) 0.69  (1.414)
PID at 6 hour (n=117, 112, 77, 75) 0.79  (1.706) 0.67  (1.094) 0.91  (1.227) 0.87  (1.554)
PID at 12 hour (n= 117, 112, 77, 75) 0.84  (1.692) 0.99  (1.411) 1.17  (1.542) 0.95  (1.550)
PID at 18 hour (n=117, 112, 77, 75) 1.19  (1.707) 1.32  (1.409) 1.44  (1.751) 1.16  (1.661)
PID at 24 hour (n=117, 112, 77, 75) 1.62  (1.866) 1.58  (1.505) 1.75  (1.808) 1.53  (1.639)
PID at 36 hour (n=117, 112, 77, 75) 1.59  (1.899) 1.65  (1.592) 1.55  (1.818) 1.32  (1.702)
PID at 48 hour (n=117, 112, 77, 75) 1.91  (1.914) 2.01  (1.562) 2.04  (1.874) 1.92  (1.937)
PID at 60 hour (n=117, 112, 77, 75) 2.41  (1.917) 2.26  (1.659) 2.56  (1.963) 2.05  (1.888)
PID at 72 hour (n=117, 112, 77, 75) 2.55  (1.989) 2.42  (1.631) 2.55  (1.977) 2.28  (1.935)
PID at 84 hour (n=113, 107, 75, 75) 2.84  (1.883) 2.68  (1.686) 3.08  (1.916) 2.68  (2.008)
PID at 96 hour (n=112, 107, 75, 74) 3.10  (1.865) 2.78  (1.890) 3.03  (2.027) 2.78  (1.882)
PID at 108 hour (n=112, 107, 75, 74) 3.34  (1.980) 3.01  (1.751) 3.48  (1.989) 3.18  (1.996)
PID at 120 hour (n=111, 107, 74, 74) 3.38  (1.864) 3.17  (1.871) 3.35  (2.044) 3.14  (1.947)
PID at 132 hour (n=110, 107, 74, 74) 3.70  (1.961) 3.53  (1.824) 3.72  (1.913) 3.47  (2.042)
PID at 144 hour (n=110, 107, 74, 74) 3.76  (2.058) 3.78  (1.870) 3.68  (1.994) 3.59  (1.979)
PID at 156 hour (n=109, 107, 74, 74) 4.17  (2.115) 4.05  (1.870) 3.95  (1.999) 3.88  (2.158)
PID at 168 hour (n=105, 104, 73, 74) 4.26  (2.103) 4.11  (1.935) 3.90  (2.122) 3.95  (2.067)
PID at 180 hour (n=105, 104, 73, 72) 4.58  (2.065) 4.45  (1.980) 4.37  (1.933) 4.08  (2.121)
PID at 192 hour (n=101, 102, 71, 72) 4.55  (2.081) 4.59  (1.916) 4.21  (2.197) 4.22  (2.023)
PID at 204 hour (n=101, 100, 71, 72) 5.17  (2.020) 4.94  (1.984) 4.87  (1.999) 4.56  (2.122)
PID at 216 hour (n=95, 100, 69, 72) 5.28  (2.239) 5.21  (2.100) 4.87  (2.029) 4.78  (1.987)
PID at 228 hour (n=95, 100, 69, 72) 5.71  (2.292) 5.62  (2.068) 5.28  (2.071) 5.01  (2.113)
PID at 240 hour (n=32, 43, 22, 42) 5.56  (2.961) 5.44  (2.196) 5.41  (2.282) 5.60  (1.951)
4.Secondary Outcome
Title PID at Rest
Hide Description

PID at rest was calculated as PI at a given time point’t’ (at rest) subtracted by the PI at baseline. Participants assessed the severity of ankle pain (PI) using the NRS scale from 0 (no pain) to 10 (extreme pain).

PI was measured at baseline (prior to treatment) and at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing.

Time Frame Baseline to 10 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population. n is number of participants analyzed for respective time point for this outcome.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Mean (Standard Deviation)
Unit of Measure: score on a scale
PI at Baseline (n=117, 112, 77, 75) 7.8  (1.55) 7.4  (1.44) 7.8  (1.60) 7.7  (1.47)
PID at 10 min. (n=117, 112, 77, 75) 0.34  (1.146) 0.43  (1.145) 0.17  (0.715) 0.25  (1.175)
PID at 30 min. (n=117, 112, 77, 75) 0.56  (1.185) 0.45  (1.314) 0.32  (0.818) 0.44  (1.328)
PID at 1 hour (n=117, 112, 77, 75) 0.64  (1.283) 0.62  (1.187) 0.48  (0.940) 0.41  (1.620)
PID at 4 hour (n=117, 112, 77, 75) 0.62  (1.413) 0.53  (1.115) 0.66  (1.071) 0.43  (1.678)
PID at 6 hour (n= 117, 112, 77, 75) 0.68  (1.473) 0.62  (1.180) 0.75  (1.183) 0.53  (1.554)
PID at 12 hour (n= 117, 112, 77, 75) 0.76  (1.501) 0.86  (1.432) 0.90  (1.429) 0.68  (1.535)
PID at 18 hour (n= 117, 112, 77, 75) 1.03  (1.597) 1.14  (1.482) 1.10  (1.594) 0.85  (1.666)
PID at 24 hour (n= 117, 112, 77, 75) 1.32  (1.579) 1.39  (1.448) 1.47  (1.535) 1.13  (1.711)
PID at 36 hour (n= 117, 112, 77, 75) 1.20  (1.549) 1.32  (1.490) 1.22  (1.635) 1.09  (1.787)
PID at 48 hour (n=117, 112, 77, 75) 1.43  (1.604) 1.53  (1.464) 1.51  (1.698) 1.45  (1.840)
PID at 60 hour (n= 117, 112, 77, 75) 1.91  (1.603) 1.83  (1.593) 1.88  (1.747) 1.64  (1.893)
PID at 72 hour (n= 117, 112, 77, 75) 1.91  (1.776) 1.91  (1.545) 1.86  (1.782) 1.76  (1.972)
PID at 84 hour (n= 113, 107, 75, 75) 2.11  (1.754) 2.19  (1.655) 2.19  (1.799) 2.03  (1.931)
PID at 96 hour (n= 112, 107, 75, 74) 2.26  (1.790) 2.17  (1.707) 2.23  (1.721) 2.00  (1.720)
PID at 108 hour (n=112, 107, 75, 74) 2.46  (1.795) 2.43  (1.833) 2.48  (1.743) 2.27  (1.889)
PID at 120 hour (n= 111, 107, 74, 74) 2.59  (1.836) 2.48  (1.750) 2.30  (1.856) 2.09  (1.917)
PID at 132 hour (n= 110, 107, 74, 74) 2.76  (1.877) 2.78  (1.819) 2.68  (1.873) 2.49  (1.967)
PID at 144 hour (n= 110, 107, 74, 74) 2.77  (1.989) 2.77  (1.789) 2.59  (1.965) 2.49  (1.918)
PID at 156 hour (n= 109, 107, 74, 74) 3.06  (2.011) 3.11  (1.755) 2.77  (1.884) 2.65  (2.129)
PID at 168 hour (n= 105, 104, 73, 74) 3.08  (2.037) 3.15  (1.805) 2.75  (1.869) 2.64  (2.004)
PID at 180 hour (n= 105, 104, 73, 72) 3.37  (2.100) 3.38  (1.871) 2.95  (1.747) 2.88  (2.103)
PID at 192 hour (n= 101, 102, 71, 72) 3.38  (2.240) 3.30  (2.067) 2.90  (1.928) 3.00  (2.035)
PID at 204 hour (n= 101, 100, 71, 72) 3.67  (2.250) 3.61  (2.030) 3.37  (1.853) 3.21  (2.021)
PID at 216 hour (n= 95, 100, 69, 72) 3.77  (2.372) 3.87  (2.028) 3.22  (2.306) 3.26  (1.936)
PID at 228 hour (n= 95, 100, 69, 72) 4.09  (2.348) 4.02  (2.074) 3.64  (2.000) 3.53  (2.083)
PID at 240 hour (n= 32, 43, 22, 42) 3.94  (2.862) 4.23  (2.010) 3.36  (2.610) 3.67  (2.149)
5.Secondary Outcome
Title Pain Relief Score (PRS)
Hide Description Pain relief was measured at each time point using a 5-point Pain Relief Scale ranging from 0-4 while at rest (Where: 0- No pain relief; 1- A little or perceptible pain relief; 2- Meaningful pain relief; 3- A lot of relief; 4- Complete relief). Participants assessed the degree of ankle pain relief using the PRS scores at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after the first day of treatment.
Time Frame Day 1 to Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population. n is number of participants analyzed for respective time point for this outcome.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Mean (Standard Deviation)
Unit of Measure: score on a scale
At 10 min. (n= 117, 111, 77, 74) 0.33  (0.616) 0.29  (0.609) 0.32  (0.498) 0.36  (0.610)
At 30 min. (n=117, 111, 77, 75) 0.44  (0.635) 0.36  (0.585) 0.49  (0.599) 0.44  (0.683)
At 1 hour (n=116, 112, 77, 75) 0.48  (0.625) 0.46  (0.599) 0.57  (0.677) 0.40  (0.717)
At 4 hour (n= 115, 110, 74, 71) 0.47  (0.626) 0.45  (0.552) 0.51  (0.579) 0.49  (0.673)
At 6 hour (n= 109, 105, 70, 69) 0.50  (0.603) 0.54  (0.605) 0.63  (0.618) 0.45  (0.607)
At 12 hour (n= 77, 89, 53, 58) 0.60  (0.591) 0.72  (0.707) 0.74  (0.684) 0.62  (0.745)
At 18 hour (n= 76, 78, 53, 57) 0.71  (0.689) 0.73  (0.715) 0.83  (0.753) 0.70  (0.680)
At 24 hour (n= 111, 105, 72, 72) 0.79  (0.662) 0.74  (0.680) 0.90  (0.754) 0.81  (0.642)
At 36 hour (n= 116, 112, 77, 74) 0.84  (0.709) 0.84  (0.705) 0.88  (0.760) 0.78  (0.781)
At 48 hour (n= 116, 112, 77, 75) 0.90  (0.806) 0.84  (0.651) 0.99  (0.716) 0.99  (0.846)
At 60 hour (n=115, 111, 77, 75) 1.07  (0.780) 1.00  (0.714) 1.16  (0.745) 0.96  (0.779)
At 72 hour (n= 114, 109, 75, 74) 0.93  (0.784) 1.06  (0.743) 1.16  (0.806) 0.97  (0.810)
At 84 hour (n= 113, 106, 75, 75) 1.07  (0.810) 1.00  (0.756) 1.25  (0.737) 1.11  (0.746)
At 96 hour (n= 112, 106, 75, 74) 1.09  (0.823) 1.03  (0.762) 1.01  (0.830) 1.09  (0.743)
At 108 hour (n= 111, 105, 75, 74) 1.18  (0.876) 1.13  (0.809) 1.28  (0.894) 1.15  (0.734)
At 120 hour (n= 111, 107, 74, 72) 1.11  (0.918) 1.14  (0.782) 1.24  (0.904) 1.10  (0.772)
At 132 hour (n= 110, 107, 73, 74) 1.34  (0.931) 1.24  (0.878) 1.34  (0.931) 1.30  (0.887)
At 144 hour (n= 110, 107, 74, 73) 1.21  (1.015) 1.21  (0.919) 1.30  (0.947) 1.27  (0.886)
At 156 hour (n= 109, 106, 74, 74) 1.41  (1.011) 1.30  (1.053) 1.47  (0.968) 1.32  (0.952)
At 168 hour (n= 105, 103, 73, 73) 1.41  (1.026) 1.31  (0.990) 1.34  (1.003) 1.40  (0.924)
6.Secondary Outcome
Title Sum of Pain Intensity Difference (SPID)
Hide Description SPID was calculated as the time weighted sum of pain intensity differences (PID) from 0 to 7 Days. PID was calculated as PI at a given time point 't' subtracted by the PI at baseline. PI was measured on NRS scale from 0 (no pain) to 10 (extreme pain). The possible range of SPID for 0-6 hours was from -60 to 60, for 0-12 hours was from -120 to 120, for 0-1 day was from -240 to 240, for 0-3 days was from -720 to 720, for 0-7 days was from -1680 to 1680. A higher value of SPID indicates greater pain relief.
Time Frame Baseline to Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Mean (Standard Deviation)
Unit of Measure: score on a scale
At 0-6 hours 4.16  (9.299) 3.19  (5.862) 4.72  (6.306) 4.37  (8.287)
At 0-12 hours 9.19  (18.788) 9.13  (13.284) 11.74  (14.675) 10.05  (16.706)
At 0-1 days 26.01  (38.722) 26.54  (28.497) 30.91  (34.158) 26.21  (34.877)
At 1 to 3 days 101.54  (87.184) 100.07  (71.085) 104.26  (83.689) 90.88  (82.626)
At 0 to 7 days 451.12  (265.919) 452.44  (244.488) 464.96  (281.243) 438.45  (287.369)
7.Secondary Outcome
Title Time of Onset of Pain Relief (TOPR)
Hide Description TOPR was measured by time when participants reported PRS ≥ 1, i.e. a “little” or “perceptible” pain relief’.
Time Frame Baseline to 10 days (end of study)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Median (Full Range)
Unit of Measure: Hours
1.03
(0.2 to 157.0)
4.00
(0.2 to 168.0)
1.00
(0.2 to 94.3)
4.00
(0.2 to 187.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5404
Comments P-value from chi-square test of survival analysis
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.81 to 1.48
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to reach perceptible pain relief. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 3% Menthol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4639
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.67 to 1.20
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to reach perceptible pain relief. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 1% Diclofenac Sodium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5118
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.84 to 1.43
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to reach perceptible pain relief. The 95% confidence intervals of cox proportional hazard ratio.
8.Secondary Outcome
Title Time of Onset of Meaningful Pain Relief (TOMR)
Hide Description TOMR was measured by time when participants reported PRS ≥ 2, i.e. “some” or “meaningful” pain relief
Time Frame up to 10 days (end of study)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participants to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participants to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participants to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participants to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Median (Full Range)
Unit of Measure: Hours
92.50
(0.2 to 203.8)
76.83
(0.2 to 184.1)
72.00
(0.2 to 203.5)
93.50
(0.2 to 203.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6918
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.67 to 1.31
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to reach perceptible pain relief. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 3% Menthol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2389
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.87 to 1.73
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to reach perceptible pain relief. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 1% Diclofenac Sodium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9817
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.74 to 1.37
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to reach perceptible pain relief. The 95% confidence intervals of cox proportional hazard ratio.
9.Secondary Outcome
Title Time of Onset of Cooling Sensation (TOCS)
Hide Description Time of onset of cooling sensation measured by time when subjects reported to have a ‘cooling effect as an enhancement of pain relief’. To assess this endpoint, participants were asked at 10, 30 minutes and at 1, 4, 6 hours post first dose “Do you feel a cooling sensation at the injured ankle from the study gel?
Time Frame up to 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Median (Full Range)
Unit of Measure: Hours
0.17
(0.17 to 6.0)
0.17
(0.17 to 6.0)
0.17
(0.17 to 6.0)
0.17
(0.17 to 6.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7003
Comments P-value from chi-square test of survival analysis
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.79 to 1.43
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to cooling sensation. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 3% Menthol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9565
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.75 to 1.35
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to cooling sensation. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 1% Diclofenac Sodium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6216
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.82 to 1.40
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to cooling sensation. The 95% confidence intervals of cox proportional hazard ratio.
10.Secondary Outcome
Title Total Pain Relief (TOTPAR)
Hide Description TOTPAR was calculated as sum of the products of PRS with time interval from one time point to the other. PRS was measured at each time point on a scale: 0= No pain relief, 1= A little or perceptible pain relief, 2= Meaningful pain relief, 3= A lot of relief, 4= Complete relief. The possible range of TOTPAR for 0-6 hours was from 0 to 24, for 0-12 hours was from 0 to 48, for 0-24 hours was from 0 to 96, for 0-72 hours was from 0 to 288, for 24-72 hours was from 0 to 192 and for 0-168 hours was from 0 to 672.
Time Frame Baseline to 168 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Mean (Standard Deviation)
Unit of Measure: PRS Score (0 – 4 scale)
0-6 hours 2.81  (3.162) 2.64  (2.902) 3.27  (3.176) 2.75  (3.184)
0-12 hours 6.86  (6.125) 6.81  (6.178) 8.02  (7.045) 6.35  (6.732)
0- 24 hours 16.04  (12.048) 16.14  (12.479) 18.85  (14.517) 15.71  (13.146)
0-72 hours 60.14  (37.867) 61.24  (35.877) 66.69  (40.360) 58.75  (41.724)
24-72 hours 44.10  (29.344) 45.11  (26.431) 47.84  (29.102) 43.04  (31.570)
0-168 hours 172.97  (98.838) 170.73  (97.187) 184.17  (102.787) 174.00  (94.917)
11.Secondary Outcome
Title Skin Temperature
Hide Description Skin temperature was measured by thermal imaging.
Time Frame At 10, 30, 60 minutes, 4 and 6 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 11 10 6 6
Mean (Standard Deviation)
Unit of Measure: degree celsius (°C)
At 10 min. 27.69  (3.706) 29.31  (2.610) 29.92  (2.118) 30.93  (2.842)
At 30 min. 28.26  (3.161) 29.81  (2.595) 30.50  (2.117) 31.47  (3.386)
At 60 min. 28.64  (2.986) 30.74  (2.781) 30.22  (2.388) 31.78  (3.213)
At 240 min. 30.52  (2.880) 31.26  (2.981) 31.15  (3.221) 31.57  (2.700)
At 360 min. 31.02  (2.951) 31.53  (3.299) 31.27  (3.925) 32.07  (3.482)
12.Secondary Outcome
Title Ankle Swelling
Hide Description Ankle swelling measured by "figure of eight" method of injured ankle.
Time Frame Day 1 (baseline), 3, and 7
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Mean (Standard Deviation)
Unit of Measure: Millimeters
At Day 1 573.9  (57.77) 573.6  (50.20) 577.1  (55.35) 576.1  (50.19)
At Day 3 566.2  (57.03) 566.9  (49.55) 567.0  (56.48) 565.4  (52.67)
At Day 7 558.3  (56.02) 558.8  (46.37) 558.4  (56.88) 557.0  (50.85)
13.Secondary Outcome
Title Time to Complete Recovery
Hide Description Time to complete recovery measured as the day with complete relief of ankle pain (Participant-rated NRS scores were 0 for pain intensity at rest and pain) and swelling (Participants did not have any apparent swelling nor experience any pain or limitation of movement of the injured ankle as determined by the Principal Investigator or designee during the course of an ankle exam).
Time Frame up to 240 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 117 112 77 75
Median (Full Range)
Unit of Measure: Hours
240.00
(17.0 to 240.0)
240.00
(48.2 to 240.0)
240.00
(53.2 to 240.0)
240.00
(145.5 to 240.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0408
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 2.43
Confidence Interval (2-Sided) 95%
1.04 to 5.70
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to complete pain relief. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 3% Menthol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4507
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
0.65 to 2.65
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to complete pain relief. The 95% confidence intervals of cox proportional hazard ratio.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 1% Diclofenac Sodium+3% Menthol, 1% Diclofenac Sodium
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3150
Comments P-value from chi-square test of survival analysis.
Method chi-square test of survival analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox proportional hazard ratio
Estimated Value 1.38
Confidence Interval (2-Sided) 95%
0.73 to 2.61
Estimation Comments Cox proportional hazard ratio of survival time, i.e. time to complete pain relief. The 95% confidence intervals of cox proportional hazard ratio.
14.Secondary Outcome
Title Patient's Global Assessment in Response to Treatment (PGART)
Hide Description PGART was measured at the end of study in a scale from 0-4 (Where: 0- Poor; 1- Fair; 2- Good; 3- Very Good; 4- Excellent)
Time Frame up to Day 10
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who fulfilled all the study entry criteria, received the study treatment and had at least one post-baseline efficacy assessment. This analysis was conducted on ITT population.
Arm/Group Title 1% Diclofenac Sodium+3% Menthol 1% Diclofenac Sodium 3% Menthol Placebo
Hide Arm/Group Description:
1% diclofenac sodium+3% menthol gel was supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
1% diclofenac sodium with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
3% menthol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Placebo with 0.09% methanol gel was supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
Overall Number of Participants Analyzed 115 111 75 75
Measure Type: Number
Unit of Measure: Participants
Poor=0 3 13 6 9
Fair=1 24 20 12 14
Good=2 44 46 26 27
Very Good=3 35 26 26 21
Excellent=4 9 6 5 4
Time Frame Up to 3 weeks of administration of investigational product
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 1% Diclofenac Sodium Plus 3% Menthol 1% Diclofenac Sodium Plus 0.09% Menthol 3% Menthol Placebo With 0.09% Menthol Gel
Hide Arm/Group Description 1% diclofenac sodium plus 3% menthol gel supplied in 30 gram (g) tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. 1% diclofenac sodium plus 0.09% menthol gel supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. 3% menthol gel supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days. Placebo with 0.09% menthol gel supplied in 30g tubes sufficient for each participant to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
All-Cause Mortality
1% Diclofenac Sodium Plus 3% Menthol 1% Diclofenac Sodium Plus 0.09% Menthol 3% Menthol Placebo With 0.09% Menthol Gel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
1% Diclofenac Sodium Plus 3% Menthol 1% Diclofenac Sodium Plus 0.09% Menthol 3% Menthol Placebo With 0.09% Menthol Gel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/117 (0.00%)   0/112 (0.00%)   0/77 (0.00%)   0/75 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
1% Diclofenac Sodium Plus 3% Menthol 1% Diclofenac Sodium Plus 0.09% Menthol 3% Menthol Placebo With 0.09% Menthol Gel
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   43/117 (36.75%)   26/112 (23.21%)   22/77 (28.57%)   17/75 (22.67%) 
Ear and labyrinth disorders         
VERTIGO   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
Gastrointestinal disorders         
ABDOMINAL PAIN   0/117 (0.00%)  1/112 (0.89%)  0/77 (0.00%)  0/75 (0.00%) 
DIARRHOEA   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
NAUSEA   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
VOMITING   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
General disorders         
APPLICATION SITE DRYNESS   15/117 (12.82%)  7/112 (6.25%)  3/77 (3.90%)  4/75 (5.33%) 
APPLICATION SITE PAIN   7/117 (5.98%)  0/112 (0.00%)  2/77 (2.60%)  1/75 (1.33%) 
APPLICATION SITE PRURITUS   5/117 (4.27%)  3/112 (2.68%)  1/77 (1.30%)  1/75 (1.33%) 
APPLICATION SITE ERYTHEMA   4/117 (3.42%)  1/112 (0.89%)  2/77 (2.60%)  0/75 (0.00%) 
APPLICATION SITE ECZEMA   2/117 (1.71%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
APPLICATION SITE DISCOLOURATION   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
APPLICATION SITE RASH   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
APPLICATION SITE REACTION   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
APPLICATION SITE VESICLES   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
ASTHENIA   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
NECROSIS   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
APPLICATION SITE BURN   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
APPLICATION SITE HYPERSENSITIVITY   0/117 (0.00%)  1/112 (0.89%)  0/77 (0.00%)  0/75 (0.00%) 
APPLICATION SITE SWELLING   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
Immune system disorders         
HYPERSENSITIVITY   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
Infections and infestations         
NASOPHARYNGITIS   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
PYODERMA   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
SINUSITIS   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
Injury, poisoning and procedural complications         
SKIN ABRASION   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
ARTHROPOD STING   0/117 (0.00%)  1/112 (0.89%)  0/77 (0.00%)  0/75 (0.00%) 
MUSCLE INJURY   0/117 (0.00%)  0/112 (0.00%)  0/77 (0.00%)  1/75 (1.33%) 
Musculoskeletal and connective tissue disorders         
ARTHRALGIA   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
BACK PAIN   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  2/75 (2.67%) 
BONE SWELLING   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
EXOSTOSIS   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
OSTEOARTHRITIS   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
Nervous system disorders         
HEADACHE   4/117 (3.42%)  2/112 (1.79%)  4/77 (5.19%)  3/75 (4.00%) 
BURNING SENSATION   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  1/75 (1.33%) 
HYPOAESTHESIA   0/117 (0.00%)  1/112 (0.89%)  0/77 (0.00%)  0/75 (0.00%) 
Skin and subcutaneous tissue disorders         
DRY SKIN   10/117 (8.55%)  10/112 (8.93%)  10/77 (12.99%)  4/75 (5.33%) 
PRURITUS   7/117 (5.98%)  4/112 (3.57%)  3/77 (3.90%)  1/75 (1.33%) 
ERYTHEMA   6/117 (5.13%)  2/112 (1.79%)  3/77 (3.90%)  1/75 (1.33%) 
BLISTER   1/117 (0.85%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
DERMATITIS   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
DERMATITIS CONTACT   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
SKIN EXFOLIATION   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
SKIN WRINKLING   1/117 (0.85%)  0/112 (0.00%)  0/77 (0.00%)  0/75 (0.00%) 
ECZEMA   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
RASH   0/117 (0.00%)  1/112 (0.89%)  0/77 (0.00%)  0/75 (0.00%) 
RASH VESICULAR   0/117 (0.00%)  0/112 (0.00%)  0/77 (0.00%)  1/75 (1.33%) 
SKIN REACTION   0/117 (0.00%)  0/112 (0.00%)  1/77 (1.30%)  0/75 (0.00%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02100670     History of Changes
Other Study ID Numbers: 202179
RH01805 ( Other Identifier: GSK )
First Submitted: March 27, 2014
First Posted: April 1, 2014
Results First Submitted: June 2, 2016
Results First Posted: January 12, 2018
Last Update Posted: January 12, 2018