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Clinical Trial Results:
A Clinical Study to Assess the Efficacy and Onset of Pain Relief of Topical MFC51123 Diclofenac-Menthol Gel versus Controls in Ankle Sprain

Summary
EudraCT number	2013-000992-33
Trial protocol	DE
Global end of trial date	22 Mar 2015

Results information
Results version number	v1(current)
This version publication date	14 Jul 2016
First version publication date	14 Jul 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

RH01805

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlakosmithKline

Sponsor organisation address

1500 Littleton Road, Parsippany, United States, NJ 07054

Public contact

GSK CH Clinical Trials, GlaxoSmithKline Consumer Healthcare, +44 1932826987, rd.gskch-clinical-trials@gsk.com

Scientific contact

GSK CH Clinical Trials, GlaxoSmithKline Consumer Healthcare, +44 1932826987, rd.gskch-clinical-trials@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Apr 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Mar 2015

Was the trial ended prematurely?

Main objective of the trial

To assess efficacy of MFC51123 gel over placebo as measured by Area Under the Curve of Pain Intensity on Movement (walking 5 steps on flat surface) for the period from 24 to 72 hours of treatment (AUC1-3days).

Protection of trial subjects

The study was conducted according to the ethical principles of the Declaration of Helsinki. The study drug was to be discontinued if continuing would result in a significant safety risk for the subject as per the protocol.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Sep 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 385

Worldwide total number of subjects

385

EEA total number of subjects

385

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

372

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects were recruited at 16 centers in the Germany.

Screening details

The study population consisted of a representative group of male and female subjects aged minimum of 16 years and maximum of 63 years suffering from ankle sprain. Of the 388 subjects screened, 385 were randomized in the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Diclofenac plus(+) Menthol

Arm description

1% Diclofenac sodium and 3% menthol gel was supplied in 30 gram (g) tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Arm type

Experimental

Investigational medicinal product name

1% diclofenac sodium+ 3% menthol gel

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Subjects were instructed to apply approximately 4 grams of the assigned topical gel product 4 times daily to the injured ankle. The subject were instructed to fill the circle on a the Gel Strip, a 90mm x 50mm piece of glycine paper designed to gauge the amount of gel to apply for a single dose.

Diclofenac

Arm description

1% Diclofenac sodium + 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Arm type

Experimental

Investigational medicinal product name

1% diclofenac sodium

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Menthol

Arm description

3% menthol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Arm type

Active comparator

Investigational medicinal product name

3% menthol gel

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Placebo

Arm description

Placebo with 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Gel

Routes of administration

Topical use

Dosage and administration details

Number of subjects in period 1	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Started	118	113	78	76
Completed	105	106	74	75
Not completed	13	7	4	1
Consent withdrawn by subject	-	1	1	-
Protocol violation	-	1	-	1
Other Reason	2	2	-	-
Adverse Events	10	3	3	-
Lost to follow-up	1	-	-	-

Baseline characteristics

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Reporting group title

Diclofenac plus(+) Menthol

Reporting group description

1% Diclofenac sodium and 3% menthol gel was supplied in 30 gram (g) tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

Diclofenac

Reporting group description

1% Diclofenac sodium + 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

Menthol

Reporting group description

3% menthol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

Placebo

Reporting group description

Placebo with 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo	Total
Number of subjects	118	113	78	76	385
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	32.3 ± 11.82	32.2 ± 11.43	33.7 ± 12.09	33 ± 11.61	-
Gender categorical
Units: Subjects
Female	50	41	39	36	166
Male	68	72	39	40	219

End points

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Reporting group title

Diclofenac plus(+) Menthol

Reporting group description

1% Diclofenac sodium and 3% menthol gel was supplied in 30 gram (g) tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

Diclofenac

Reporting group description

1% Diclofenac sodium + 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

Menthol

Reporting group description

3% menthol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

Placebo

Reporting group description

Placebo with 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Primary: 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

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End point 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 ^[1]

End point description

AUC of pain intensity (PI) on movement was measured by numerical rating scale (NRS) during the 48 hour time interval from Day 1 to 3. AUC1-3 day was calculated based on trapezoidal method. PI was measured in NRS scale from 0 (no pain) to 10 (extreme pain). Subjects assessed the severity of ankle pain using 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.

End point type

Primary

End point timeframe

Upto 72 hours

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint required the descriptive and statistical data for Diclofenac/Methanol gel and Placebo gel only, not for all the treatments group involved in this study.

End point values	Diclofenac plus(+) Menthol	Placebo
Number of subjects analysed	117	75
Units: Score on scale
arithmetic mean (standard deviation)	276.97 ± 111.356	282.88 ± 100.958

1% Diclofenac sodium (sod.) +3% Menthol vs Placebo

Comparison groups

Diclofenac plus(+) Menthol v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4144

Method

ANCOVA

Parameter type

Least square (LS) mean difference

Point estimate

-9.23

Confidence interval

level

95%

sides

2-sided

lower limit

-31.45

upper limit

12.98

Secondary: Pain Intensity Difference (PID) on Movement

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End point title

Pain Intensity Difference (PID) on Movement

End point description

PID on movement (after walking 5 steps on a flat surface), calculated as PI at a given time 't' subtracted by the PI at baseline, measured on movement using NRS scale. Participants assessed the severity of ankle pain using the NRS scale 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. 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.

End point type

Secondary

End point timeframe

Baseline to 10 days

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on scale
arithmetic mean (standard deviation)
At Baseline (117, 112, 77, 75)	7.8 ± 1.55	7.4 ± 1.44	7.8 ± 1.6	7.7 ± 1.47
At 10 min. (117, 112, 77, 75)	7.54 ± 1.808	7.23 ± 1.571	7.47 ± 1.854	7.37 ± 1.6
At 30 min. (117, 112, 77, 75)	7.33 ± 1.974	7.06 ± 1.689	7.26 ± 1.852	7.15 ± 1.706
At 1 hour (117, 112, 77, 75)	7.21 ± 2.05	6.92 ± 1.761	7.12 ± 2.039	7.05 ± 1.8
At 4 hour (117, 112, 77, 75)	7.06 ± 2.147	6.94 ± 1.802	6.96 ± 2.112	7 ± 1.748
At 6 hour (117, 112, 77, 75)	6.98 ± 2.141	6.75 ± 1.758	6.84 ± 2.213	6.83 ± 1.855
At 12 hour (117, 112, 77, 75)	6.93 ± 2.148	6.43 ± 1.93	6.58 ± 2.347	6.75 ± 2.08
At 18 hour (117, 112, 77, 75)	6.58 ± 2.163	6.1 ± 2.022	6.31 ± 2.429	6.53 ± 2.107
At 24 hour (117, 112, 77, 75)	6.15 ± 2.273	5.84 ± 2.078	6 ± 2.487	6.16 ± 2.137
At 36 hour (117, 112, 77, 75)	6.18 ± 2.427	5.77 ± 2.058	6.21 ± 2.478	6.37 ± 2.065
At 48 hour (117, 112, 77, 75)	5.85 ± 2.447	5.41 ± 2.099	5.71 ± 2.665	5.77 ± 2.436
At 60 hour (117, 112, 77, 75)	5.36 ± 2.398	5.16 ± 2.192	5.19 ± 2.616	5.64 ± 2.21
At 72 hour (117, 112, 77, 75)	5.22 ± 2.492	5 ± 2.144	5.21 ± 2.657	5.41 ± 2.218
At 84 hour (113, 107, 75, 75)	4.92 ± 2.342	4.77 ± 2.108	4.65 ± 2.549	5.01 ± 2.293
At 96 hour (112, 107, 75, 74)	4.64 ± 2.189	4.67 ± 2.162	4.71 ± 2.572	4.88 ± 2.196
At 108 hour (112, 107, 75, 74)	4.38 ± 2.306	4.44 ± 2.093	4.25 ± 2.526	4.49 ± 2.115
At 120 hour (111, 107, 74, 74)	4.35 ± 2.131	4.28 ± 2.145	4.36 ± 2.594	4.53 ± 1.995
At 132 hour (110, 107, 74, 74)	4.03 ± 2.178	3.92 ± 2.001	4 ± 2.449	4.19 ± 2.194
At 144 hour (110, 107, 74, 74)	3.96 ± 2.209	3.67 ± 2.05	4.04 ± 2.551	4.07 ± 2.179
At 156 hour (109, 107, 74, 74)	3.54 ± 2.154	3.4 ± 2.041	3.77 ± 2.497	3.78 ± 2.198
At 168 hour (105, 104, 73, 74)	3.5 ± 2.034	3.33 ± 1.923	3.81 ± 2.548	3.72 ± 2.123
At 180 hour (105, 104, 73, 72)	3.18 ± 2.129	2.98 ± 1.961	3.34 ± 2.341	3.6 ± 2.046
At 192 hour (101, 102, 71, 72)	3.18 ± 1.962	2.85 ± 1.9	3.56 ± 2.506	3.46 ± 2.055
At 204 hour (101, 100, 71, 72)	2.56 ± 1.824	2.51 ± 1.91	2.9 ± 2.331	3.13 ± 2.096
At 216 hour (95, 100, 69, 72)	2.48 ± 1.85	2.27 ± 1.89	2.9 ± 2.177	2.9 ± 1.944
At 228 hour (95, 100, 69, 72)	2.06 ± 1.844	1.86 ± 1.831	2.49 ± 2.266	2.67 ± 1.891
At 240 hour (32, 43, 22, 42)	2.13 ± 2.136	2 ± 2.204	1.95 ± 2.058	2.12 ± 1.626

No statistical analyses for this end point

Secondary: Pain Intensity Difference (PID) at Rest

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End point title

Pain Intensity Difference (PID) at Rest

End point description

PID at rest was calculated as PI at a given time ‘t’ at rest subtracted by the PI at baseline measured using NRS scale at baseline (prior to treatment) and at 10, 30 min. and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing.

End point type

Secondary

End point timeframe

Baseline to 10 days

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on scale
arithmetic mean (standard deviation)
At Baseline (117, 112, 77, 75)	7.8 ± 1.55	7.4 ± 1.44	7.8 ± 1.6	7.7 ± 1.47
At 10 min. (117, 112, 77, 75)	0.34 ± 1.146	0.43 ± 1.145	0.17 ± 0.715	0.25 ± 1.175
At 30 min. (117, 112, 77, 75)	0.56 ± 1.185	0.45 ± 1.314	0.32 ± 0.818	0.44 ± 1.328
At 1 hour (117, 112, 77, 75)	0.64 ± 1.283	0.62 ± 1.187	0.48 ± 0.94	0.41 ± 1.62
At 4 hour (117, 112, 77, 75)	0.62 ± 1.413	0.53 ± 1.115	0.66 ± 1.071	0.43 ± 1.678
At 6 hour (117, 112, 77, 75)	0.68 ± 1.473	0.62 ± 1.18	0.75 ± 1.183	0.53 ± 1.554
At 12 hour (117, 112, 77, 75)	0.76 ± 1.501	0.86 ± 1.432	0.9 ± 1.429	0.68 ± 1.535
At 18 hour (117, 112, 77, 75)	1.03 ± 1.597	1.14 ± 1.482	1.1 ± 1.594	0.85 ± 1.666
At 24 hour (117, 112, 77, 75)	1.32 ± 1.579	1.39 ± 1.448	1.47 ± 1.535	1.13 ± 1.711
At 36 hour (117, 112, 77, 75)	1.2 ± 1.549	1.32 ± 1.49	1.22 ± 1.635	1.09 ± 1.787
At 48 hour (117, 112, 77, 75)	1.43 ± 1.604	1.53 ± 1.464	1.51 ± 1.698	1.45 ± 1.84
At 60 hour (117, 112, 77, 75)	1.91 ± 1.603	1.83 ± 1.593	1.88 ± 1.747	1.64 ± 1.893
At 72 hour (117, 112, 77, 75)	1.91 ± 1.776	1.91 ± 1.545	1.86 ± 1.782	1.76 ± 1.972
At 84 hour (113, 107, 75, 75)	2.11 ± 1.754	2.19 ± 1.655	2.19 ± 1.799	2.03 ± 1.931
At 96 hour (112, 107, 75, 74)	2.26 ± 1.79	2.17 ± 1.707	2.23 ± 1.721	2 ± 1.72
At 108 hour (112, 107, 75, 74)	2.46 ± 1.795	2.43 ± 1.833	2.48 ± 1.743	2.27 ± 1.889
At 120 hour (111, 107, 74, 74)	2.59 ± 1.836	2.48 ± 1.75	2.3 ± 1.856	2.09 ± 1.917
At 132 hour (110, 107, 74, 74)	2.76 ± 1.877	2.78 ± 1.819	2.68 ± 1.873	2.49 ± 1.967
At 144 hour (110, 107, 74, 74)	2.77 ± 1.989	2.77 ± 1.789	2.59 ± 1.965	2.49 ± 1.918
At 156 hour (109, 107, 74, 74)	3.06 ± 2.011	3.11 ± 1.755	2.77 ± 1.884	2.65 ± 2.129
At 168 hour (105, 104, 73, 74)	3.08 ± 2.037	3.15 ± 1.805	2.75 ± 1.869	2.64 ± 2.004
At 180 hour (105, 104, 73, 72)	3.37 ± 2.1	3.38 ± 1.871	2.95 ± 1.747	2.88 ± 2.103
At 192 hour (101, 102, 71, 72)	3.38 ± 2.24	3.3 ± 2.067	2.9 ± 1.928	3 ± 2.035
At 204 hour (101, 100, 71, 72)	3.67 ± 2.25	3.61 ± 2.03	3.37 ± 1.853	3.21 ± 2.021
At 216 hour (95, 100, 69, 72)	3.77 ± 2.372	3.87 ± 2.028	3.22 ± 2.306	3.26 ± 1.936
At 228 hour (95, 100, 69, 72)	4.09 ± 2.348	4.02 ± 2.074	3.64 ± 2	3.53 ± 2.083
At 240 hour (32, 43, 22, 42)	3.94 ± 2.862	4.23 ± 2.01	3.36 ± 2.61	3.67 ± 2.149

No statistical analyses for this end point

Secondary: Pain Relief Score (PRS)

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End point title

Pain Relief Score (PRS)

End point description

PRS 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). Subjects assessed the degree of ankle pain relief using the PRS scores at 10, 30 min. and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after the first day of treatment.

End point type

Secondary

End point timeframe

Day 1 to Day 7

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on scale
arithmetic mean (standard deviation)
At 10 min. (117, 111, 77, 74)	0.33 ± 0.616	0.29 ± 0.609	0.32 ± 0.498	0.36 ± 0.61
At 30 min. (117, 111, 77, 75)	0.44 ± 0.635	0.36 ± 0.585	0.49 ± 0.599	0.44 ± 0.683
At 1 hour (116, 112, 77, 75)	0.48 ± 0.625	0.46 ± 0.599	0.57 ± 0.677	0.4 ± 0.717
At 4 hour (115, 110, 74, 71)	0.47 ± 0.626	0.45 ± 0.552	0.51 ± 0.579	0.49 ± 0.673
At 6 hour (109, 105, 70, 69)	0.5 ± 0.603	0.54 ± 0.605	0.63 ± 0.618	0.45 ± 0.607
At 12 hour (77, 89, 53, 58)	0.6 ± 0.591	0.72 ± 0.707	0.74 ± 0.684	0.62 ± 0.745
At 18 hour (76, 78, 53, 57)	0.71 ± 0.689	0.73 ± 0.715	0.83 ± 0.753	0.7 ± 0.68
At 24 hour (111, 105, 72, 72)	0.79 ± 0.662	0.74 ± 0.68	0.9 ± 0.754	0.81 ± 0.642
At 36 hour (116, 112, 77, 74)	0.84 ± 0.709	0.84 ± 0.705	0.88 ± 0.76	0.78 ± 0.781
At 48 hour (116, 112, 77, 75)	0.9 ± 0.806	0.84 ± 0.651	0.99 ± 0.716	0.99 ± 0.846
At 60 hour (115, 111, 77, 75)	1.07 ± 0.78	1 ± 0.714	1.16 ± 0.745	0.96 ± 0.779
At 72 hour (114, 109, 75, 74)	0.93 ± 0.784	1.06 ± 0.743	1.16 ± 0.806	0.97 ± 0.81
At 84 hour (113, 106, 75, 75)	1.07 ± 0.81	1 ± 0.756	1.25 ± 0.737	1.11 ± 0.746
At 96 hour (112, 106, 75, 74)	1.09 ± 0.823	1.03 ± 0.762	1.01 ± 0.83	1.09 ± 0.743
At 108 hour (111, 105, 75, 74)	1.18 ± 0.876	1.13 ± 0.809	1.28 ± 0.894	1.15 ± 0.734
At 120 hour (111, 107, 74, 72)	1.11 ± 0.918	1.14 ± 0.782	1.24 ± 0.904	1.1 ± 0.772
At 132 hour (110, 107, 73, 74)	1.34 ± 0.931	1.24 ± 0.878	1.34 ± 0.931	1.3 ± 0.887
At 144 hour (110, 107, 74, 73)	1.21 ± 1.015	1.21 ± 0.919	1.3 ± 0.947	1.27 ± 0.886
At 156 hour (109, 106, 74, 74)	1.41 ± 1.011	1.3 ± 1.053	1.47 ± 0.968	1.32 ± 0.952
At 168 hour (105, 103, 73, 73)	1.41 ± 1.026	1.31 ± 0.99	1.34 ± 1.003	1.4 ± 0.924

No statistical analyses for this end point

Secondary: Sum of Pain Intensity Difference (SPID)

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End point title

Sum of Pain Intensity Difference (SPID)

End point description

SPID was measured as SPIDt = ∑PIDt x (timet - timet-1) (h) by PID for periods 0-6, 0-12 hours and 0 to 1, 1 to 3 and 0 to 7 days after initial treatment between treatment groups.

End point type

Secondary

End point timeframe

0-6, 0-12 hours, 0 to 1, 1-3 days, 0-7 days

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on a scale
arithmetic mean (standard deviation)
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

No statistical analyses for this end point

Secondary: Time of Onset of Pain Relief (TOPR)

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End point title

Time of Onset of Pain Relief (TOPR)

End point description

TOPR was measured by the time when subjects reported PRS ≥ 1, i.e. a “little” or “perceptible” pain relief.

End point type

Secondary

End point timeframe

Baseline to Day 3

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on a scale
median (full range (min-max))	1.03 (0.2 to 157)	4 (0.2 to 168)	1 (0.2 to 94.3)	4 (0.2 to 187.5)

1% Diclofenac sod. +3% Menthol vs Placebo

Comparison groups

Diclofenac plus(+) Menthol v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5404

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

0.81

upper limit

1.48

1% Diclofenac sod. +3% Menthol vs 3% Menthol

Comparison groups

Diclofenac plus(+) Menthol v Menthol

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4639

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.2

1% Diclofenac sod. +3% Menthol vs 1% Diclofenac

Comparison groups

Diclofenac plus(+) Menthol v Diclofenac

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5118

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

1.09

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.43

Secondary: Time of Onset of meaningful Pain Relief (TOMR)

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End point title

Time of Onset of meaningful Pain Relief (TOMR)

End point description

TOMR was measured by the time when subjects reported PRS ≥ 2, i.e. “some” or “meaningful” pain relief.

End point type

Secondary

End point timeframe

Baseline to Day 4

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on a scale
median (full range (min-max))	92.5 (0.2 to 203.8)	76.83 (0.2 to 184.1)	72 (0.2 to 203.5)	93.5 (0.2 to 203)

1% Diclofenac sod. +3% Menthol vs Placebo

Comparison groups

Diclofenac plus(+) Menthol v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6918

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.67

upper limit

1.31

1% Diclofenac sod. +3% Menthol vs 3% Menthol

Comparison groups

Diclofenac plus(+) Menthol v Menthol

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2389

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

1.23

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.73

1%Diclofenac sod.+3% Menthol vs 1% Diclofenac sod.

Comparison groups

Diclofenac plus(+) Menthol v Diclofenac

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9817

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.74

upper limit

1.37

Secondary: Time of Onset of Cooling Sensation (TOCS)

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End point title

Time of Onset of Cooling Sensation (TOCS)

End point description

Time of onset of cooling sensation was measured by the time when subjects reported to have a ‘cooling effect as an enhancement of pain relief’. To assess this endpoint subjects were asked at 10, 30 min. and at 1, 4, 6 hours post first dose “Have you felt a cooling sensation at the injured ankle from the study gel?”

End point type

Secondary

End point timeframe

Baseline to 6 hours

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on a scale
median (full range (min-max))	0.17 (0.17 to 6)	0.17 (0.17 to 6)	0.17 (0.17 to 6)	0.17 (0.17 to 6)

1% Diclofenac sod. +3% Menthol vs Placebo

Comparison groups

Diclofenac plus(+) Menthol v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.7003

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.79

upper limit

1.43

1% Diclofenac sod.+3% Menthol vs 3% Menthol

Comparison groups

Menthol v Diclofenac plus(+) Menthol

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9565

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

1.01

Confidence interval

level

95%

sides

2-sided

lower limit

0.75

upper limit

1.35

1% Diclofenac Sod +3% Menthol vs 1%Diclofenac Sod

Comparison groups

Diclofenac plus(+) Menthol v Diclofenac

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.6216

Method

Chi-squared

Parameter type

Cox proportional hazard

Point estimate

1.07

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

1.4

Secondary: Total Pain Relief (TOTPAR)

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End point title

Total Pain Relief (TOTPAR)

End point description

TOTPAR was calculated as sum of the products of PRS with time interval from one time point to other. Descriptive analysis was provided for each time point.

End point type

Secondary

End point timeframe

0 - 6, 0 - 12 hours and 0 - 1, 1 - 3, and 0 - 7 days

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on a scale
arithmetic mean (standard deviation)
At 0 - 6 hours	2.81 ± 3.162	2.64 ± 2.902	3.27 ± 3.176	2.75 ± 3.184
At 0 - 12 hours	6.86 ± 6.125	6.81 ± 6.178	8.02 ± 7.045	6.35 ± 6.732
At 0 - 1 days	16.04 ± 12.048	16.14 ± 12.479	18.85 ± 14.517	15.71 ± 13.146
At 1 - 3 days	44.1 ± 29.344	45.11 ± 26.431	47.84 ± 29.102	43.04 ± 31.57
At 0 - 7 days	172.97 ± 98.838	170.73 ± 97.187	184.17 ± 102.787	174 ± 94.917

No statistical analyses for this end point

Secondary: Skin Temperature

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End point title

Skin Temperature

End point description

Skin temperature was measured by thermal imaging.

End point type

Secondary

End point timeframe

At 10, 30, 60 minute (min.) and 4 and 6 hours

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	11	10	6	6
Units: degree Celsius (°C)
arithmetic mean (standard deviation)
At 10 min.	27.69 ± 3.706	29.31 ± 2.61	29.92 ± 2.118	30.93 ± 2.842
At 30 min.	28.26 ± 3.161	29.81 ± 2.595	30.5 ± 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 4 hours	30.52 ± 2.88	31.26 ± 2.981	31.15 ± 3.221	31.57 ± 2.7
At 6 hours	31.02 ± 2.951	31.53 ± 3.299	31.27 ± 3.925	32.07 ± 3.482

No statistical analyses for this end point

Secondary: Ankle Swelling

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End point title

Ankle Swelling

End point description

Reduction in ankle swelling as change from baseline measured by “figure of eight” method of injured ankle measurement. No overall statistical analyses for this endpoint.

End point type

Secondary

End point timeframe

Days 1, 3 and 7

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: Score on a scale
arithmetic mean (standard deviation)
Day 1	573.9 ± 57.77	573.6 ± 50.2	577.1 ± 55.35	576.1 ± 50.19
Day 3	566.2 ± 57.03	566.9 ± 49.55	567 ± 56.48	565.4 ± 52.67
Day 7	558.3 ± 56.02	558.8 ± 46.37	558.4 ± 56.88	557 ± 50.85

No statistical analyses for this end point

Secondary: Time to Complete Recovery

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End point title

Time to Complete Recovery

End point description

Time to complete recovery was measured as the day with complete relief of ankle pain (subject-rated NRS scores were 0 for pain intensity at rest and pain) and swelling (subject 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).

End point type

Secondary

End point timeframe

Baseline to Day 10

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: score on a scale
median (full range (min-max))	240 (17 to 240)	240 (48.2 to 240)	240 (53.2 to 240)	240 (145.5 to 240)

% Diclofenac Sod+3% Menthol vs Placebo

Comparison groups

Diclofenac plus(+) Menthol v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0408

Method

t-test, 2-sided

Parameter type

Cox proportional hazard

Point estimate

2.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

5.7

1% Diclofenac Sod+3% Menthol vs 3% Menthol

Comparison groups

Diclofenac plus(+) Menthol v Menthol

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4507

Method

t-test, 2-sided

Parameter type

Cox proportional hazard

Point estimate

1.31

Confidence interval

level

95%

sides

2-sided

lower limit

0.65

upper limit

2.65

1% Diclofenac Sod+3% Menthol vs 1% Diclofenac Sod

Comparison groups

Diclofenac plus(+) Menthol v Diclofenac

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.315

Method

t-test, 2-sided

Parameter type

Cox proportional hazard

Point estimate

1.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

2.61

Secondary: Patient’s Global Assessment in Response to Treatment (PGART)

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End point title

Patient’s Global Assessment in Response to Treatment (PGART)

End point 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)

End point type

Secondary

End point timeframe

Baseline to Day 10

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: number of 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

Diclofenac Sodium + Methanol vs Placebo

Comparison groups

Diclofenac plus(+) Menthol v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.1114

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.23

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.52

Diclofenac + Methanol vs Methanol

Comparison groups

Diclofenac plus(+) Menthol v Menthol

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.5808

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.37

Diclofenac + Methanol vs Diclofenac

Comparison groups

Diclofenac plus(+) Menthol v Placebo

Number of subjects included in analysis

192

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.03

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

0.29

Confidence interval

level

95%

sides

2-sided

lower limit

0.03

upper limit

0.55

Secondary: AUC1-3 days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo

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End point title

AUC1-3 days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo

End point 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.

End point type

Secondary

End point timeframe

Baseline to 72 hours

End point values	Diclofenac plus(+) Menthol	Diclofenac	Menthol	Placebo
Number of subjects analysed	117	112	77	75
Units: score on a scale
arithmetic mean (standard deviation)	276.97 ± 111.356	261.11 ± 96.791	272.65 ± 118.196	282.88 ± 100.958

1% diclofenac+3% menthol vs 1% diclofenac

Comparison groups

Diclofenac plus(+) Menthol v Diclofenac

Number of subjects included in analysis

229

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8761

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.58

Confidence interval

level

95%

sides

2-sided

lower limit

-18.34

upper limit

21.5

1% diclofenac+3% menthol vs 3% menthol

Comparison groups

Diclofenac plus(+) Menthol v Menthol

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.8164

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

2.61

Confidence interval

level

95%

sides

2-sided

lower limit

-19.46

upper limit

24.67

1% diclofenac vs 3% menthol

Comparison groups

Diclofenac v Menthol

Number of subjects included in analysis

189

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.9279

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

1.03

Confidence interval

level

95%

sides

2-sided

lower limit

-21.27

upper limit

23.33

1% Diclofenac vs Placebo

Comparison groups

Diclofenac v Placebo

Number of subjects included in analysis

187

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.3442

Method

ANCOVA

Parameter type

LS mean difference

Point estimate

-10.81

Confidence interval

level

95%

sides

2-sided

lower limit

-33.26

upper limit

11.64

Adverse events

Top of page

Timeframe for reporting adverse events

Baseline upto Day 10 of administration of investigational product

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

0.0

Reporting group title

1% Diclofenac plus + 3% Menthol

Reporting group description

1% Diclofenac sodium+ 3% menthol gel was supplied in 30 gram (g) tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

1% Diclofenac

Reporting group description

1% Diclofenac sodium + 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

3% Menthol

Reporting group description

3% menthol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Reporting group title

Placebo

Reporting group description

Placebo with 0.09% methanol gel was supplied in 30g tubes for each subject to apply 4g of gel topically to the injured ankle region four times daily for up to 10 days.

Serious adverse events	1% Diclofenac plus + 3% Menthol	1% Diclofenac	3% Menthol	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	1% Diclofenac plus + 3% Menthol	1% Diclofenac	3% Menthol	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	43 / 117 (36.75%)	26 / 112 (23.21%)	22 / 77 (28.57%)	17 / 75 (22.67%)
Injury, poisoning and procedural complications
Arthropod Sting
subjects affected / exposed	0 / 117 (0.00%)	1 / 112 (0.89%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	0	2	0	0
Skin Abrasion
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Muscle Injury
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	0 / 77 (0.00%)	1 / 75 (1.33%)
occurrences all number	0	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	4 / 117 (3.42%)	2 / 112 (1.79%)	4 / 77 (5.19%)	3 / 75 (4.00%)
occurrences all number	4	2	4	3
Hypoaesthesia
subjects affected / exposed	0 / 117 (0.00%)	1 / 112 (0.89%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	0	1	0	0
Burning Sensation
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	1 / 75 (1.33%)
occurrences all number	1	0	0	1
General disorders and administration site conditions
Application Site Dryness
subjects affected / exposed	15 / 117 (12.82%)	7 / 112 (6.25%)	3 / 77 (3.90%)	4 / 75 (5.33%)
occurrences all number	15	7	3	4
Application site pain
subjects affected / exposed	7 / 117 (5.98%)	0 / 112 (0.00%)	2 / 77 (2.60%)	1 / 75 (1.33%)
occurrences all number	7	0	2	1
Application site pruritus
subjects affected / exposed	5 / 117 (4.27%)	3 / 112 (2.68%)	1 / 77 (1.30%)	1 / 75 (1.33%)
occurrences all number	5	3	1	1
Application Site Erythema
subjects affected / exposed	4 / 117 (3.42%)	1 / 112 (0.89%)	2 / 77 (2.60%)	0 / 75 (0.00%)
occurrences all number	4	1	2	0
Application Site Eczema
subjects affected / exposed	2 / 117 (1.71%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	2	0	0	0
Application Site Discolouration
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Application Site Rash
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Application Site Reaction
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Application Site Vesicles
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Asthenia
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Necrosis
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Application Site Hypersensitivity
subjects affected / exposed	0 / 117 (0.00%)	1 / 112 (0.89%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	0	2	0	0
Application Site Burn
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Application Site Swelling
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	0 / 117 (0.00%)	1 / 112 (0.89%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	0	1	0	0
Diarrhoea
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	2	0
Nausea
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Vomiting
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Skin and subcutaneous tissue disorders
Dry Skin
subjects affected / exposed	10 / 117 (8.55%)	10 / 112 (8.93%)	10 / 77 (12.99%)	4 / 75 (5.33%)
occurrences all number	10	10	10	4
Pruritus
subjects affected / exposed	7 / 117 (5.98%)	4 / 112 (3.57%)	3 / 77 (3.90%)	1 / 75 (1.33%)
occurrences all number	8	5	3	1
Erythema
subjects affected / exposed	6 / 117 (5.13%)	2 / 112 (1.79%)	3 / 77 (3.90%)	1 / 75 (1.33%)
occurrences all number	6	2	3	1
Blister
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	1	0	1	0
Dermatitis
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Dermatitis Contact
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Skin Exfoliation
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Skin Wrinkling
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Eczema
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Rash
subjects affected / exposed	0 / 117 (0.00%)	1 / 112 (0.89%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	0	1	0	0
Rash Vesicular
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	0 / 77 (0.00%)	1 / 75 (1.33%)
occurrences all number	0	0	0	1
Skin Reaction
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Back Pain
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	2 / 75 (2.67%)
occurrences all number	0	0	1	2
Bone Swelling
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Exostosis
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Osteoarthritis
subjects affected / exposed	0 / 117 (0.00%)	0 / 112 (0.00%)	1 / 77 (1.30%)	0 / 75 (0.00%)
occurrences all number	0	0	1	0
Infections and infestations
Nasopharyngitis
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Pyoderma
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0
Sinusitis
subjects affected / exposed	1 / 117 (0.85%)	0 / 112 (0.00%)	0 / 77 (0.00%)	0 / 75 (0.00%)
occurrences all number	1	0	0	0

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Clinical Study to Assess the Efficacy and Onset of Pain Relief of Topical MFC51123 Diclofenac-Menthol Gel versus Controls in Ankle Sprain

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 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

Primary: 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

Secondary: Pain Intensity Difference (PID) on Movement

Secondary: Pain Intensity Difference (PID) on Movement

Secondary: Pain Intensity Difference (PID) at Rest

Secondary: Pain Intensity Difference (PID) at Rest

Secondary: Pain Relief Score (PRS)

Secondary: Pain Relief Score (PRS)

Secondary: Sum of Pain Intensity Difference (SPID)

Secondary: Sum of Pain Intensity Difference (SPID)

Secondary: Time of Onset of Pain Relief (TOPR)

Secondary: Time of Onset of Pain Relief (TOPR)

Secondary: Time of Onset of meaningful Pain Relief (TOMR)

Secondary: Time of Onset of meaningful Pain Relief (TOMR)

Secondary: Time of Onset of Cooling Sensation (TOCS)

Secondary: Time of Onset of Cooling Sensation (TOCS)

Secondary: Total Pain Relief (TOTPAR)

Secondary: Total Pain Relief (TOTPAR)

Secondary: Skin Temperature

Secondary: Skin Temperature

Secondary: Ankle Swelling

Secondary: Ankle Swelling

Secondary: Time to Complete Recovery

Secondary: Time to Complete Recovery

Secondary: Patient’s Global Assessment in Response to Treatment (PGART)

Secondary: Patient’s Global Assessment in Response to Treatment (PGART)

Secondary: AUC1-3 days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo

Secondary: AUC1-3 days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Clinical Study to Assess the Efficacy and Onset of Pain Relief of Topical MFC51123 Diclofenac-Menthol Gel versus Controls in Ankle Sprain