Pain
Conditions
Brief summary
This Phase III pivotal efficacy study will assess efficacy and onset of pain relief of MFC51123 gel vs. placebo and MFC51123 gel vs. 1% diclofenac gel and 3% menthol gel in participants with an ankle sprain to support topical MFC51123 gel registration.
Detailed description
This is a multi-center, randomized, double-blind, repeat-dose, placebo-controlled, parallel-group trial in participants with ankle sprain. Eligible participants will be randomly assigned to one of four treatment groups (1% diclofenac plus 3% menthol gel, 1% diclofenac plus 0.09% menthol gel, 3% menthol gel or placebo gel with 0.09% menthol). Treatment will be self-administered by participants four times daily on an out-patient basis. Participants will rate pain intensity score (NRS) at rest and on movement, pain relief score (PRS) and cooling and soothing sensations. After leaving the clinic, participants will continue to complete scheduled pain intensity and pain relief assessments and answer questions about cooling sensation by answering questions in a paper diary card. The investigator (or designee) will measure the ankle swelling via the 'figure-of-eight' method on treatment Days 1 (at Baseline), 3, 7 and 10. Participants will continue treatment until they are pain free or for up to 10 days, whichever occurs first. At the end of the treatment, participants will be assessed for function of the injured joint by the investigator. In addition, the participants will evaluate treatment satisfaction, sensory features of the gel and provide a global assessment of the treatment by using a questionnaire.
Interventions
DRUG1% diclofenac sodium plus 3% menthol
To be applied four times daily for 10 days.
DRUG1% diclofenac sodium plus 0.09% menthol
To be applied four times daily for 10 days.
DRUG3% menthol
To be applied four times daily for 10 days.
DRUGPlacebo with 0.09% menthol gel
To be applied four times daily for 10 days.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age: 16-65 years * Good general and mental health * Grade I or Grade II acute sprain of the lateral ankle within 24 hours of Visit 1, a pain intensity score of the ankle sprain that is ≥ 5 as measured on an 11-point numerical rating scale, and a peri-malleolar edema (sub-malleolar perimeter difference of ≥ 20mm between injured and uninjured ankle * Females of child-bearing age practicing a reliable method of contraception
Exclusion criteria
* Pregnant or breast-feeding females * If participant has treated the ankle sprain with treatment such as oral or other topical pain relief medications, massage or physical therapy since experiencing the ankle sprain * Acute or chronic pain disorders, which may confound the study pain evaluations * Participant has has injury to both ankles or to both medial and lateral ligaments of the same ankle * Known or suspected hypersensitivity, allergy, intolerance or contraindication to the use of any of the study medications * Participant has a medical history of renal or hepatic disease, a current active peptic ulcer or a history of upper gastrointestinal bleeding or perforation related to previous NSAID therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | up to 72 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity Difference (PID) on Movement | Baseline to 10 days | 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. |
| PID at Rest | Baseline to 10 days | 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. |
| Pain Relief Score (PRS) | Day 1 to Day 7 | 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. |
| Sum of Pain Intensity Difference (SPID) | Baseline to Day 7 | 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 of Onset of Pain Relief (TOPR) | Baseline to 10 days (end of study) | TOPR was measured by time when participants reported PRS ≥ 1, i.e. a little or perceptible pain relief'. |
| Time of Onset of Meaningful Pain Relief (TOMR) | up to 10 days (end of study) | TOMR was measured by time when participants reported PRS ≥ 2, i.e. some or meaningful pain relief |
| AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo | up to 72 hours | 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. |
| Total Pain Relief (TOTPAR) | Baseline to 168 hours | 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. |
| Skin Temperature | At 10, 30, 60 minutes, 4 and 6 hours | Skin temperature was measured by thermal imaging. |
| Ankle Swelling | Day 1 (baseline), 3, and 7 | Ankle swelling measured by figure of eight method of injured ankle. |
| Time to Complete Recovery | up to 240 hours | 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). |
| Patient's Global Assessment in Response to Treatment (PGART) | up to Day 10 | 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 of Onset of Cooling Sensation (TOCS) | up to 6 hours | 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? |
Countries
Germany
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 1% Diclofenac Sodium+3% Menthol 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. | 117 |
| 1% Diclofenac Sodium 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. | 112 |
| 3% Menthol 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. | 77 |
| Placebo 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. | 75 |
| Total | 381 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 10 | 3 | 3 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | No swelling no pain | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 |
| Overall Study | Poor Efficacy | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal of Consent | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | 1% Diclofenac Sodium+3% Menthol | 1% Diclofenac Sodium | 3% Menthol | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 32.4 Years STANDARD_DEVIATION 11.83 | 32.1 Years STANDARD_DEVIATION 11.4 | 33.8 Years STANDARD_DEVIATION 12.15 | 33.2 Years STANDARD_DEVIATION 11.63 | 32.8 Years STANDARD_DEVIATION 11.7 |
| Sex: Female, Male Female | 50 Participants | 41 Participants | 39 Participants | 35 Participants | 165 Participants |
| Sex: Female, Male Male | 67 Participants | 71 Participants | 38 Participants | 40 Participants | 216 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 43 / 117 | 26 / 112 | 22 / 77 | 17 / 75 |
| serious Total, serious adverse events | 0 / 117 | 0 / 112 | 0 / 77 | 0 / 75 |
Outcome results
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
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | 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 | 276.97 NRS Score (0 - 10 scale) * hrs | Standard Deviation 111.356 |
| Placebo | 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 | 282.88 NRS Score (0 - 10 scale) * hrs | Standard Deviation 100.958 |
p-value: 0.414495% CI: [-31.45, 12.98]ANCOVA
Secondary
Ankle Swelling
Ankle swelling measured by figure of eight method of injured ankle.
Time frame: Day 1 (baseline), 3, and 7
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Ankle Swelling | At Day 1 | 573.9 Millimeters | Standard Deviation 57.77 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Ankle Swelling | At Day 7 | 558.3 Millimeters | Standard Deviation 56.02 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Ankle Swelling | At Day 3 | 566.2 Millimeters | Standard Deviation 57.03 |
| Placebo | Ankle Swelling | At Day 1 | 573.6 Millimeters | Standard Deviation 50.2 |
| Placebo | Ankle Swelling | At Day 7 | 558.8 Millimeters | Standard Deviation 46.37 |
| Placebo | Ankle Swelling | At Day 3 | 566.9 Millimeters | Standard Deviation 49.55 |
| 3% Menthol | Ankle Swelling | At Day 3 | 567.0 Millimeters | Standard Deviation 56.48 |
| 3% Menthol | Ankle Swelling | At Day 1 | 577.1 Millimeters | Standard Deviation 55.35 |
| 3% Menthol | Ankle Swelling | At Day 7 | 558.4 Millimeters | Standard Deviation 56.88 |
| Placebo | Ankle Swelling | At Day 1 | 576.1 Millimeters | Standard Deviation 50.19 |
| Placebo | Ankle Swelling | At Day 7 | 557.0 Millimeters | Standard Deviation 50.85 |
| Placebo | Ankle Swelling | At Day 3 | 565.4 Millimeters | Standard Deviation 52.67 |
Secondary
AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo | 276.97 NRS Score (0 - 10 scale) * hrs | Standard Deviation 111.356 |
| Placebo | AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo | 261.11 NRS Score (0 - 10 scale) * hrs | Standard Deviation 96.791 |
| 3% Menthol | AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo | 272.65 NRS Score (0 - 10 scale) * hrs | Standard Deviation 118.196 |
| Placebo | AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo | 282.88 NRS Score (0 - 10 scale) * hrs | Standard Deviation 100.958 |
p-value: 0.876195% CI: [-18.34, 21.5]ANCOVA
p-value: 0.816495% CI: [-19.46, 24.67]ANCOVA
p-value: 0.927995% CI: [-21.27, 23.33]ANCOVA
p-value: 0.344295% CI: [-33.26, 11.64]ANCOVA
Secondary
Pain Intensity Difference (PID) on Movement
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PI at Baseline (n=117, 112, 77, 75) | 7.8 score on scale | Standard Deviation 1.55 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 18 hour (n=117, 112, 77, 75) | 1.19 score on scale | Standard Deviation 1.707 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 132 hour (n=110, 107, 74, 74) | 3.70 score on scale | Standard Deviation 1.961 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 30 min. (n=117, 112, 77, 75) | 0.44 score on scale | Standard Deviation 1.302 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 96 hour (n=112, 107, 75, 74) | 3.10 score on scale | Standard Deviation 1.865 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 24 hour (n=117, 112, 77, 75) | 1.62 score on scale | Standard Deviation 1.866 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 4 hour (n=117, 112, 77, 75) | 0.71 score on scale | Standard Deviation 1.64 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 228 hour (n=95, 100, 69, 72) | 5.71 score on scale | Standard Deviation 2.292 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 204 hour (n=101, 100, 71, 72) | 5.17 score on scale | Standard Deviation 2.02 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 36 hour (n=117, 112, 77, 75) | 1.59 score on scale | Standard Deviation 1.899 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 144 hour (n=110, 107, 74, 74) | 3.76 score on scale | Standard Deviation 2.058 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 120 hour (n=111, 107, 74, 74) | 3.38 score on scale | Standard Deviation 1.864 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 6 hour (n=117, 112, 77, 75) | 0.79 score on scale | Standard Deviation 1.706 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 48 hour (n=117, 112, 77, 75) | 1.91 score on scale | Standard Deviation 1.914 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 168 hour (n=105, 104, 73, 74) | 4.26 score on scale | Standard Deviation 2.103 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 108 hour (n=112, 107, 75, 74) | 3.34 score on scale | Standard Deviation 1.98 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 192 hour (n=101, 102, 71, 72) | 4.55 score on scale | Standard Deviation 2.081 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 60 hour (n=117, 112, 77, 75) | 2.41 score on scale | Standard Deviation 1.917 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 216 hour (n=95, 100, 69, 72) | 5.28 score on scale | Standard Deviation 2.239 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 1 hour (n=117, 112, 77, 75) | 0.56 score on scale | Standard Deviation 1.348 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 12 hour (n= 117, 112, 77, 75) | 0.84 score on scale | Standard Deviation 1.692 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 72 hour (n=117, 112, 77, 75) | 2.55 score on scale | Standard Deviation 1.989 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 156 hour (n=109, 107, 74, 74) | 4.17 score on scale | Standard Deviation 2.115 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 240 hour (n=32, 43, 22, 42) | 5.56 score on scale | Standard Deviation 2.961 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 180 hour (n=105, 104, 73, 72) | 4.58 score on scale | Standard Deviation 2.065 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 84 hour (n=113, 107, 75, 75) | 2.84 score on scale | Standard Deviation 1.883 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 10 min. (n=117, 112, 77, 75) | 0.23 score on scale | Standard Deviation 1.078 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 84 hour (n=113, 107, 75, 75) | 2.68 score on scale | Standard Deviation 1.686 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 168 hour (n=105, 104, 73, 74) | 4.11 score on scale | Standard Deviation 1.935 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 96 hour (n=112, 107, 75, 74) | 2.78 score on scale | Standard Deviation 1.89 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 108 hour (n=112, 107, 75, 74) | 3.01 score on scale | Standard Deviation 1.751 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 156 hour (n=109, 107, 74, 74) | 4.05 score on scale | Standard Deviation 1.87 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 120 hour (n=111, 107, 74, 74) | 3.17 score on scale | Standard Deviation 1.871 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 4 hour (n=117, 112, 77, 75) | 0.48 score on scale | Standard Deviation 1.057 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 132 hour (n=110, 107, 74, 74) | 3.53 score on scale | Standard Deviation 1.824 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 10 min. (n=117, 112, 77, 75) | 0.19 score on scale | Standard Deviation 0.855 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 144 hour (n=110, 107, 74, 74) | 3.78 score on scale | Standard Deviation 1.87 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 216 hour (n=95, 100, 69, 72) | 5.21 score on scale | Standard Deviation 2.1 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 6 hour (n=117, 112, 77, 75) | 0.67 score on scale | Standard Deviation 1.094 |
| Placebo | Pain Intensity Difference (PID) on Movement | PI at Baseline (n=117, 112, 77, 75) | 7.4 score on scale | Standard Deviation 1.44 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 12 hour (n= 117, 112, 77, 75) | 0.99 score on scale | Standard Deviation 1.411 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 18 hour (n=117, 112, 77, 75) | 1.32 score on scale | Standard Deviation 1.409 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 204 hour (n=101, 100, 71, 72) | 4.94 score on scale | Standard Deviation 1.984 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 24 hour (n=117, 112, 77, 75) | 1.58 score on scale | Standard Deviation 1.505 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 30 min. (n=117, 112, 77, 75) | 0.36 score on scale | Standard Deviation 0.967 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 36 hour (n=117, 112, 77, 75) | 1.65 score on scale | Standard Deviation 1.592 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 240 hour (n=32, 43, 22, 42) | 5.44 score on scale | Standard Deviation 2.196 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 192 hour (n=101, 102, 71, 72) | 4.59 score on scale | Standard Deviation 1.916 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 48 hour (n=117, 112, 77, 75) | 2.01 score on scale | Standard Deviation 1.562 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 228 hour (n=95, 100, 69, 72) | 5.62 score on scale | Standard Deviation 2.068 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 60 hour (n=117, 112, 77, 75) | 2.26 score on scale | Standard Deviation 1.659 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 180 hour (n=105, 104, 73, 72) | 4.45 score on scale | Standard Deviation 1.98 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 72 hour (n=117, 112, 77, 75) | 2.42 score on scale | Standard Deviation 1.631 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 1 hour (n=117, 112, 77, 75) | 0.50 score on scale | Standard Deviation 1.022 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 204 hour (n=101, 100, 71, 72) | 4.87 score on scale | Standard Deviation 1.999 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PI at Baseline (n=117, 112, 77, 75) | 7.8 score on scale | Standard Deviation 1.6 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 10 min. (n=117, 112, 77, 75) | 0.29 score on scale | Standard Deviation 0.886 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 30 min. (n=117, 112, 77, 75) | 0.49 score on scale | Standard Deviation 0.868 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 1 hour (n=117, 112, 77, 75) | 0.64 score on scale | Standard Deviation 1.146 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 4 hour (n=117, 112, 77, 75) | 0.79 score on scale | Standard Deviation 1.128 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 6 hour (n=117, 112, 77, 75) | 0.91 score on scale | Standard Deviation 1.227 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 12 hour (n= 117, 112, 77, 75) | 1.17 score on scale | Standard Deviation 1.542 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 18 hour (n=117, 112, 77, 75) | 1.44 score on scale | Standard Deviation 1.751 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 24 hour (n=117, 112, 77, 75) | 1.75 score on scale | Standard Deviation 1.808 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 36 hour (n=117, 112, 77, 75) | 1.55 score on scale | Standard Deviation 1.818 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 48 hour (n=117, 112, 77, 75) | 2.04 score on scale | Standard Deviation 1.874 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 60 hour (n=117, 112, 77, 75) | 2.56 score on scale | Standard Deviation 1.963 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 72 hour (n=117, 112, 77, 75) | 2.55 score on scale | Standard Deviation 1.977 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 84 hour (n=113, 107, 75, 75) | 3.08 score on scale | Standard Deviation 1.916 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 96 hour (n=112, 107, 75, 74) | 3.03 score on scale | Standard Deviation 2.027 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 108 hour (n=112, 107, 75, 74) | 3.48 score on scale | Standard Deviation 1.989 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 120 hour (n=111, 107, 74, 74) | 3.35 score on scale | Standard Deviation 2.044 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 132 hour (n=110, 107, 74, 74) | 3.72 score on scale | Standard Deviation 1.913 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 144 hour (n=110, 107, 74, 74) | 3.68 score on scale | Standard Deviation 1.994 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 156 hour (n=109, 107, 74, 74) | 3.95 score on scale | Standard Deviation 1.999 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 168 hour (n=105, 104, 73, 74) | 3.90 score on scale | Standard Deviation 2.122 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 180 hour (n=105, 104, 73, 72) | 4.37 score on scale | Standard Deviation 1.933 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 192 hour (n=101, 102, 71, 72) | 4.21 score on scale | Standard Deviation 2.197 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 216 hour (n=95, 100, 69, 72) | 4.87 score on scale | Standard Deviation 2.029 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 228 hour (n=95, 100, 69, 72) | 5.28 score on scale | Standard Deviation 2.071 |
| 3% Menthol | Pain Intensity Difference (PID) on Movement | PID at 240 hour (n=32, 43, 22, 42) | 5.41 score on scale | Standard Deviation 2.282 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 84 hour (n=113, 107, 75, 75) | 2.68 score on scale | Standard Deviation 2.008 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 240 hour (n=32, 43, 22, 42) | 5.60 score on scale | Standard Deviation 1.951 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 168 hour (n=105, 104, 73, 74) | 3.95 score on scale | Standard Deviation 2.067 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 72 hour (n=117, 112, 77, 75) | 2.28 score on scale | Standard Deviation 1.935 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 60 hour (n=117, 112, 77, 75) | 2.05 score on scale | Standard Deviation 1.888 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 228 hour (n=95, 100, 69, 72) | 5.01 score on scale | Standard Deviation 2.113 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 180 hour (n=105, 104, 73, 72) | 4.08 score on scale | Standard Deviation 2.121 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 48 hour (n=117, 112, 77, 75) | 1.92 score on scale | Standard Deviation 1.937 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 36 hour (n=117, 112, 77, 75) | 1.32 score on scale | Standard Deviation 1.702 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 10 min. (n=117, 112, 77, 75) | 0.32 score on scale | Standard Deviation 1.129 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 192 hour (n=101, 102, 71, 72) | 4.22 score on scale | Standard Deviation 2.023 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 24 hour (n=117, 112, 77, 75) | 1.53 score on scale | Standard Deviation 1.639 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 18 hour (n=117, 112, 77, 75) | 1.16 score on scale | Standard Deviation 1.661 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 12 hour (n= 117, 112, 77, 75) | 0.95 score on scale | Standard Deviation 1.55 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 204 hour (n=101, 100, 71, 72) | 4.56 score on scale | Standard Deviation 2.122 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 6 hour (n=117, 112, 77, 75) | 0.87 score on scale | Standard Deviation 1.554 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 4 hour (n=117, 112, 77, 75) | 0.69 score on scale | Standard Deviation 1.414 |
| Placebo | Pain Intensity Difference (PID) on Movement | PI at Baseline (n=117, 112, 77, 75) | 7.7 score on scale | Standard Deviation 1.47 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 216 hour (n=95, 100, 69, 72) | 4.78 score on scale | Standard Deviation 1.987 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 132 hour (n=110, 107, 74, 74) | 3.47 score on scale | Standard Deviation 2.042 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 1 hour (n=117, 112, 77, 75) | 0.64 score on scale | Standard Deviation 1.521 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 144 hour (n=110, 107, 74, 74) | 3.59 score on scale | Standard Deviation 1.979 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 120 hour (n=111, 107, 74, 74) | 3.14 score on scale | Standard Deviation 1.947 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 108 hour (n=112, 107, 75, 74) | 3.18 score on scale | Standard Deviation 1.996 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 30 min. (n=117, 112, 77, 75) | 0.55 score on scale | Standard Deviation 1.464 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 156 hour (n=109, 107, 74, 74) | 3.88 score on scale | Standard Deviation 2.158 |
| Placebo | Pain Intensity Difference (PID) on Movement | PID at 96 hour (n=112, 107, 75, 74) | 2.78 score on scale | Standard Deviation 1.882 |
Secondary
Pain Relief Score (PRS)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 120 hour (n= 111, 107, 74, 72) | 1.11 score on a scale | Standard Deviation 0.918 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 72 hour (n= 114, 109, 75, 74) | 0.93 score on a scale | Standard Deviation 0.784 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 4 hour (n= 115, 110, 74, 71) | 0.47 score on a scale | Standard Deviation 0.626 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 108 hour (n= 111, 105, 75, 74) | 1.18 score on a scale | Standard Deviation 0.876 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 84 hour (n= 113, 106, 75, 75) | 1.07 score on a scale | Standard Deviation 0.81 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 10 min. (n= 117, 111, 77, 74) | 0.33 score on a scale | Standard Deviation 0.616 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 96 hour (n= 112, 106, 75, 74) | 1.09 score on a scale | Standard Deviation 0.823 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 30 min. (n=117, 111, 77, 75) | 0.44 score on a scale | Standard Deviation 0.635 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 156 hour (n= 109, 106, 74, 74) | 1.41 score on a scale | Standard Deviation 1.011 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 6 hour (n= 109, 105, 70, 69) | 0.50 score on a scale | Standard Deviation 0.603 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 12 hour (n= 77, 89, 53, 58) | 0.60 score on a scale | Standard Deviation 0.591 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 144 hour (n= 110, 107, 74, 73) | 1.21 score on a scale | Standard Deviation 1.015 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 18 hour (n= 76, 78, 53, 57) | 0.71 score on a scale | Standard Deviation 0.689 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 168 hour (n= 105, 103, 73, 73) | 1.41 score on a scale | Standard Deviation 1.026 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 24 hour (n= 111, 105, 72, 72) | 0.79 score on a scale | Standard Deviation 0.662 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 1 hour (n=116, 112, 77, 75) | 0.48 score on a scale | Standard Deviation 0.625 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 132 hour (n= 110, 107, 73, 74) | 1.34 score on a scale | Standard Deviation 0.931 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 36 hour (n= 116, 112, 77, 74) | 0.84 score on a scale | Standard Deviation 0.709 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 48 hour (n= 116, 112, 77, 75) | 0.90 score on a scale | Standard Deviation 0.806 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Pain Relief Score (PRS) | At 60 hour (n=115, 111, 77, 75) | 1.07 score on a scale | Standard Deviation 0.78 |
| Placebo | Pain Relief Score (PRS) | At 120 hour (n= 111, 107, 74, 72) | 1.14 score on a scale | Standard Deviation 0.782 |
| Placebo | Pain Relief Score (PRS) | At 60 hour (n=115, 111, 77, 75) | 1.00 score on a scale | Standard Deviation 0.714 |
| Placebo | Pain Relief Score (PRS) | At 156 hour (n= 109, 106, 74, 74) | 1.30 score on a scale | Standard Deviation 1.053 |
| Placebo | Pain Relief Score (PRS) | At 108 hour (n= 111, 105, 75, 74) | 1.13 score on a scale | Standard Deviation 0.809 |
| Placebo | Pain Relief Score (PRS) | At 12 hour (n= 77, 89, 53, 58) | 0.72 score on a scale | Standard Deviation 0.707 |
| Placebo | Pain Relief Score (PRS) | At 72 hour (n= 114, 109, 75, 74) | 1.06 score on a scale | Standard Deviation 0.743 |
| Placebo | Pain Relief Score (PRS) | At 10 min. (n= 117, 111, 77, 74) | 0.29 score on a scale | Standard Deviation 0.609 |
| Placebo | Pain Relief Score (PRS) | At 168 hour (n= 105, 103, 73, 73) | 1.31 score on a scale | Standard Deviation 0.99 |
| Placebo | Pain Relief Score (PRS) | At 48 hour (n= 116, 112, 77, 75) | 0.84 score on a scale | Standard Deviation 0.651 |
| Placebo | Pain Relief Score (PRS) | At 84 hour (n= 113, 106, 75, 75) | 1.00 score on a scale | Standard Deviation 0.756 |
| Placebo | Pain Relief Score (PRS) | At 18 hour (n= 76, 78, 53, 57) | 0.73 score on a scale | Standard Deviation 0.715 |
| Placebo | Pain Relief Score (PRS) | At 96 hour (n= 112, 106, 75, 74) | 1.03 score on a scale | Standard Deviation 0.762 |
| Placebo | Pain Relief Score (PRS) | At 36 hour (n= 116, 112, 77, 74) | 0.84 score on a scale | Standard Deviation 0.705 |
| Placebo | Pain Relief Score (PRS) | At 4 hour (n= 115, 110, 74, 71) | 0.45 score on a scale | Standard Deviation 0.552 |
| Placebo | Pain Relief Score (PRS) | At 132 hour (n= 110, 107, 73, 74) | 1.24 score on a scale | Standard Deviation 0.878 |
| Placebo | Pain Relief Score (PRS) | At 1 hour (n=116, 112, 77, 75) | 0.46 score on a scale | Standard Deviation 0.599 |
| Placebo | Pain Relief Score (PRS) | At 24 hour (n= 111, 105, 72, 72) | 0.74 score on a scale | Standard Deviation 0.68 |
| Placebo | Pain Relief Score (PRS) | At 6 hour (n= 109, 105, 70, 69) | 0.54 score on a scale | Standard Deviation 0.605 |
| Placebo | Pain Relief Score (PRS) | At 30 min. (n=117, 111, 77, 75) | 0.36 score on a scale | Standard Deviation 0.585 |
| Placebo | Pain Relief Score (PRS) | At 144 hour (n= 110, 107, 74, 73) | 1.21 score on a scale | Standard Deviation 0.919 |
| 3% Menthol | Pain Relief Score (PRS) | At 84 hour (n= 113, 106, 75, 75) | 1.25 score on a scale | Standard Deviation 0.737 |
| 3% Menthol | Pain Relief Score (PRS) | At 10 min. (n= 117, 111, 77, 74) | 0.32 score on a scale | Standard Deviation 0.498 |
| 3% Menthol | Pain Relief Score (PRS) | At 30 min. (n=117, 111, 77, 75) | 0.49 score on a scale | Standard Deviation 0.599 |
| 3% Menthol | Pain Relief Score (PRS) | At 1 hour (n=116, 112, 77, 75) | 0.57 score on a scale | Standard Deviation 0.677 |
| 3% Menthol | Pain Relief Score (PRS) | At 4 hour (n= 115, 110, 74, 71) | 0.51 score on a scale | Standard Deviation 0.579 |
| 3% Menthol | Pain Relief Score (PRS) | At 6 hour (n= 109, 105, 70, 69) | 0.63 score on a scale | Standard Deviation 0.618 |
| 3% Menthol | Pain Relief Score (PRS) | At 12 hour (n= 77, 89, 53, 58) | 0.74 score on a scale | Standard Deviation 0.684 |
| 3% Menthol | Pain Relief Score (PRS) | At 18 hour (n= 76, 78, 53, 57) | 0.83 score on a scale | Standard Deviation 0.753 |
| 3% Menthol | Pain Relief Score (PRS) | At 24 hour (n= 111, 105, 72, 72) | 0.90 score on a scale | Standard Deviation 0.754 |
| 3% Menthol | Pain Relief Score (PRS) | At 36 hour (n= 116, 112, 77, 74) | 0.88 score on a scale | Standard Deviation 0.76 |
| 3% Menthol | Pain Relief Score (PRS) | At 48 hour (n= 116, 112, 77, 75) | 0.99 score on a scale | Standard Deviation 0.716 |
| 3% Menthol | Pain Relief Score (PRS) | At 60 hour (n=115, 111, 77, 75) | 1.16 score on a scale | Standard Deviation 0.745 |
| 3% Menthol | Pain Relief Score (PRS) | At 72 hour (n= 114, 109, 75, 74) | 1.16 score on a scale | Standard Deviation 0.806 |
| 3% Menthol | Pain Relief Score (PRS) | At 96 hour (n= 112, 106, 75, 74) | 1.01 score on a scale | Standard Deviation 0.83 |
| 3% Menthol | Pain Relief Score (PRS) | At 108 hour (n= 111, 105, 75, 74) | 1.28 score on a scale | Standard Deviation 0.894 |
| 3% Menthol | Pain Relief Score (PRS) | At 120 hour (n= 111, 107, 74, 72) | 1.24 score on a scale | Standard Deviation 0.904 |
| 3% Menthol | Pain Relief Score (PRS) | At 132 hour (n= 110, 107, 73, 74) | 1.34 score on a scale | Standard Deviation 0.931 |
| 3% Menthol | Pain Relief Score (PRS) | At 144 hour (n= 110, 107, 74, 73) | 1.30 score on a scale | Standard Deviation 0.947 |
| 3% Menthol | Pain Relief Score (PRS) | At 156 hour (n= 109, 106, 74, 74) | 1.47 score on a scale | Standard Deviation 0.968 |
| 3% Menthol | Pain Relief Score (PRS) | At 168 hour (n= 105, 103, 73, 73) | 1.34 score on a scale | Standard Deviation 1.003 |
| Placebo | Pain Relief Score (PRS) | At 48 hour (n= 116, 112, 77, 75) | 0.99 score on a scale | Standard Deviation 0.846 |
| Placebo | Pain Relief Score (PRS) | At 36 hour (n= 116, 112, 77, 74) | 0.78 score on a scale | Standard Deviation 0.781 |
| Placebo | Pain Relief Score (PRS) | At 156 hour (n= 109, 106, 74, 74) | 1.32 score on a scale | Standard Deviation 0.952 |
| Placebo | Pain Relief Score (PRS) | At 120 hour (n= 111, 107, 74, 72) | 1.10 score on a scale | Standard Deviation 0.772 |
| Placebo | Pain Relief Score (PRS) | At 24 hour (n= 111, 105, 72, 72) | 0.81 score on a scale | Standard Deviation 0.642 |
| Placebo | Pain Relief Score (PRS) | At 18 hour (n= 76, 78, 53, 57) | 0.70 score on a scale | Standard Deviation 0.68 |
| Placebo | Pain Relief Score (PRS) | At 30 min. (n=117, 111, 77, 75) | 0.44 score on a scale | Standard Deviation 0.683 |
| Placebo | Pain Relief Score (PRS) | At 132 hour (n= 110, 107, 73, 74) | 1.30 score on a scale | Standard Deviation 0.887 |
| Placebo | Pain Relief Score (PRS) | At 12 hour (n= 77, 89, 53, 58) | 0.62 score on a scale | Standard Deviation 0.745 |
| Placebo | Pain Relief Score (PRS) | At 6 hour (n= 109, 105, 70, 69) | 0.45 score on a scale | Standard Deviation 0.607 |
| Placebo | Pain Relief Score (PRS) | At 10 min. (n= 117, 111, 77, 74) | 0.36 score on a scale | Standard Deviation 0.61 |
| Placebo | Pain Relief Score (PRS) | At 144 hour (n= 110, 107, 74, 73) | 1.27 score on a scale | Standard Deviation 0.886 |
| Placebo | Pain Relief Score (PRS) | At 4 hour (n= 115, 110, 74, 71) | 0.49 score on a scale | Standard Deviation 0.673 |
| Placebo | Pain Relief Score (PRS) | At 84 hour (n= 113, 106, 75, 75) | 1.11 score on a scale | Standard Deviation 0.746 |
| Placebo | Pain Relief Score (PRS) | At 1 hour (n=116, 112, 77, 75) | 0.40 score on a scale | Standard Deviation 0.717 |
| Placebo | Pain Relief Score (PRS) | At 96 hour (n= 112, 106, 75, 74) | 1.09 score on a scale | Standard Deviation 0.743 |
| Placebo | Pain Relief Score (PRS) | At 72 hour (n= 114, 109, 75, 74) | 0.97 score on a scale | Standard Deviation 0.81 |
| Placebo | Pain Relief Score (PRS) | At 60 hour (n=115, 111, 77, 75) | 0.96 score on a scale | Standard Deviation 0.779 |
| Placebo | Pain Relief Score (PRS) | At 168 hour (n= 105, 103, 73, 73) | 1.40 score on a scale | Standard Deviation 0.924 |
| Placebo | Pain Relief Score (PRS) | At 108 hour (n= 111, 105, 75, 74) | 1.15 score on a scale | Standard Deviation 0.734 |
Secondary
Patient's Global Assessment in Response to Treatment (PGART)
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
Population: 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 | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Very Good=3 | 35 Participants | — |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Fair=1 | 24 Participants | — |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Excellent=4 | 9 Participants | — |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Good=2 | 44 Participants | — |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Poor=0 | 3 Participants | 0.948 |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Good=2 | 46 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Very Good=3 | 26 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Excellent=4 | 6 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Fair=1 | 20 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Poor=0 | 13 Participants | 1.051 |
| 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Good=2 | 26 Participants | — |
| 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Poor=0 | 6 Participants | 1.04 |
| 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Fair=1 | 12 Participants | — |
| 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Very Good=3 | 26 Participants | — |
| 3% Menthol | Patient's Global Assessment in Response to Treatment (PGART) | Excellent=4 | 5 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Very Good=3 | 21 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Fair=1 | 14 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Poor=0 | 9 Participants | 1.084 |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Good=2 | 27 Participants | — |
| Placebo | Patient's Global Assessment in Response to Treatment (PGART) | Excellent=4 | 4 Participants | — |
Secondary
PID at Rest
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PI at Baseline (n=117, 112, 77, 75) | 7.8 score on a scale | Standard Deviation 1.55 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 18 hour (n= 117, 112, 77, 75) | 1.03 score on a scale | Standard Deviation 1.597 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 132 hour (n= 110, 107, 74, 74) | 2.76 score on a scale | Standard Deviation 1.877 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 30 min. (n=117, 112, 77, 75) | 0.56 score on a scale | Standard Deviation 1.185 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 96 hour (n= 112, 107, 75, 74) | 2.26 score on a scale | Standard Deviation 1.79 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 24 hour (n= 117, 112, 77, 75) | 1.32 score on a scale | Standard Deviation 1.579 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 4 hour (n=117, 112, 77, 75) | 0.62 score on a scale | Standard Deviation 1.413 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 228 hour (n= 95, 100, 69, 72) | 4.09 score on a scale | Standard Deviation 2.348 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 204 hour (n= 101, 100, 71, 72) | 3.67 score on a scale | Standard Deviation 2.25 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 36 hour (n= 117, 112, 77, 75) | 1.20 score on a scale | Standard Deviation 1.549 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 144 hour (n= 110, 107, 74, 74) | 2.77 score on a scale | Standard Deviation 1.989 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 120 hour (n= 111, 107, 74, 74) | 2.59 score on a scale | Standard Deviation 1.836 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 6 hour (n= 117, 112, 77, 75) | 0.68 score on a scale | Standard Deviation 1.473 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 48 hour (n=117, 112, 77, 75) | 1.43 score on a scale | Standard Deviation 1.604 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 168 hour (n= 105, 104, 73, 74) | 3.08 score on a scale | Standard Deviation 2.037 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 108 hour (n=112, 107, 75, 74) | 2.46 score on a scale | Standard Deviation 1.795 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 192 hour (n= 101, 102, 71, 72) | 3.38 score on a scale | Standard Deviation 2.24 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 60 hour (n= 117, 112, 77, 75) | 1.91 score on a scale | Standard Deviation 1.603 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 216 hour (n= 95, 100, 69, 72) | 3.77 score on a scale | Standard Deviation 2.372 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 1 hour (n=117, 112, 77, 75) | 0.64 score on a scale | Standard Deviation 1.283 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 12 hour (n= 117, 112, 77, 75) | 0.76 score on a scale | Standard Deviation 1.501 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 72 hour (n= 117, 112, 77, 75) | 1.91 score on a scale | Standard Deviation 1.776 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 156 hour (n= 109, 107, 74, 74) | 3.06 score on a scale | Standard Deviation 2.011 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 240 hour (n= 32, 43, 22, 42) | 3.94 score on a scale | Standard Deviation 2.862 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 180 hour (n= 105, 104, 73, 72) | 3.37 score on a scale | Standard Deviation 2.1 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 84 hour (n= 113, 107, 75, 75) | 2.11 score on a scale | Standard Deviation 1.754 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | PID at Rest | PID at 10 min. (n=117, 112, 77, 75) | 0.34 score on a scale | Standard Deviation 1.146 |
| Placebo | PID at Rest | PID at 84 hour (n= 113, 107, 75, 75) | 2.19 score on a scale | Standard Deviation 1.655 |
| Placebo | PID at Rest | PID at 168 hour (n= 105, 104, 73, 74) | 3.15 score on a scale | Standard Deviation 1.805 |
| Placebo | PID at Rest | PID at 96 hour (n= 112, 107, 75, 74) | 2.17 score on a scale | Standard Deviation 1.707 |
| Placebo | PID at Rest | PID at 108 hour (n=112, 107, 75, 74) | 2.43 score on a scale | Standard Deviation 1.833 |
| Placebo | PID at Rest | PID at 156 hour (n= 109, 107, 74, 74) | 3.11 score on a scale | Standard Deviation 1.755 |
| Placebo | PID at Rest | PID at 120 hour (n= 111, 107, 74, 74) | 2.48 score on a scale | Standard Deviation 1.75 |
| Placebo | PID at Rest | PID at 4 hour (n=117, 112, 77, 75) | 0.53 score on a scale | Standard Deviation 1.115 |
| Placebo | PID at Rest | PID at 132 hour (n= 110, 107, 74, 74) | 2.78 score on a scale | Standard Deviation 1.819 |
| Placebo | PID at Rest | PID at 10 min. (n=117, 112, 77, 75) | 0.43 score on a scale | Standard Deviation 1.145 |
| Placebo | PID at Rest | PID at 144 hour (n= 110, 107, 74, 74) | 2.77 score on a scale | Standard Deviation 1.789 |
| Placebo | PID at Rest | PID at 216 hour (n= 95, 100, 69, 72) | 3.87 score on a scale | Standard Deviation 2.028 |
| Placebo | PID at Rest | PID at 6 hour (n= 117, 112, 77, 75) | 0.62 score on a scale | Standard Deviation 1.18 |
| Placebo | PID at Rest | PI at Baseline (n=117, 112, 77, 75) | 7.4 score on a scale | Standard Deviation 1.44 |
| Placebo | PID at Rest | PID at 12 hour (n= 117, 112, 77, 75) | 0.86 score on a scale | Standard Deviation 1.432 |
| Placebo | PID at Rest | PID at 18 hour (n= 117, 112, 77, 75) | 1.14 score on a scale | Standard Deviation 1.482 |
| Placebo | PID at Rest | PID at 204 hour (n= 101, 100, 71, 72) | 3.61 score on a scale | Standard Deviation 2.03 |
| Placebo | PID at Rest | PID at 24 hour (n= 117, 112, 77, 75) | 1.39 score on a scale | Standard Deviation 1.448 |
| Placebo | PID at Rest | PID at 30 min. (n=117, 112, 77, 75) | 0.45 score on a scale | Standard Deviation 1.314 |
| Placebo | PID at Rest | PID at 36 hour (n= 117, 112, 77, 75) | 1.32 score on a scale | Standard Deviation 1.49 |
| Placebo | PID at Rest | PID at 240 hour (n= 32, 43, 22, 42) | 4.23 score on a scale | Standard Deviation 2.01 |
| Placebo | PID at Rest | PID at 192 hour (n= 101, 102, 71, 72) | 3.30 score on a scale | Standard Deviation 2.067 |
| Placebo | PID at Rest | PID at 48 hour (n=117, 112, 77, 75) | 1.53 score on a scale | Standard Deviation 1.464 |
| Placebo | PID at Rest | PID at 228 hour (n= 95, 100, 69, 72) | 4.02 score on a scale | Standard Deviation 2.074 |
| Placebo | PID at Rest | PID at 60 hour (n= 117, 112, 77, 75) | 1.83 score on a scale | Standard Deviation 1.593 |
| Placebo | PID at Rest | PID at 180 hour (n= 105, 104, 73, 72) | 3.38 score on a scale | Standard Deviation 1.871 |
| Placebo | PID at Rest | PID at 72 hour (n= 117, 112, 77, 75) | 1.91 score on a scale | Standard Deviation 1.545 |
| Placebo | PID at Rest | PID at 1 hour (n=117, 112, 77, 75) | 0.62 score on a scale | Standard Deviation 1.187 |
| 3% Menthol | PID at Rest | PID at 204 hour (n= 101, 100, 71, 72) | 3.37 score on a scale | Standard Deviation 1.853 |
| 3% Menthol | PID at Rest | PI at Baseline (n=117, 112, 77, 75) | 7.8 score on a scale | Standard Deviation 1.6 |
| 3% Menthol | PID at Rest | PID at 10 min. (n=117, 112, 77, 75) | 0.17 score on a scale | Standard Deviation 0.715 |
| 3% Menthol | PID at Rest | PID at 30 min. (n=117, 112, 77, 75) | 0.32 score on a scale | Standard Deviation 0.818 |
| 3% Menthol | PID at Rest | PID at 1 hour (n=117, 112, 77, 75) | 0.48 score on a scale | Standard Deviation 0.94 |
| 3% Menthol | PID at Rest | PID at 4 hour (n=117, 112, 77, 75) | 0.66 score on a scale | Standard Deviation 1.071 |
| 3% Menthol | PID at Rest | PID at 6 hour (n= 117, 112, 77, 75) | 0.75 score on a scale | Standard Deviation 1.183 |
| 3% Menthol | PID at Rest | PID at 12 hour (n= 117, 112, 77, 75) | 0.90 score on a scale | Standard Deviation 1.429 |
| 3% Menthol | PID at Rest | PID at 18 hour (n= 117, 112, 77, 75) | 1.10 score on a scale | Standard Deviation 1.594 |
| 3% Menthol | PID at Rest | PID at 24 hour (n= 117, 112, 77, 75) | 1.47 score on a scale | Standard Deviation 1.535 |
| 3% Menthol | PID at Rest | PID at 36 hour (n= 117, 112, 77, 75) | 1.22 score on a scale | Standard Deviation 1.635 |
| 3% Menthol | PID at Rest | PID at 48 hour (n=117, 112, 77, 75) | 1.51 score on a scale | Standard Deviation 1.698 |
| 3% Menthol | PID at Rest | PID at 60 hour (n= 117, 112, 77, 75) | 1.88 score on a scale | Standard Deviation 1.747 |
| 3% Menthol | PID at Rest | PID at 72 hour (n= 117, 112, 77, 75) | 1.86 score on a scale | Standard Deviation 1.782 |
| 3% Menthol | PID at Rest | PID at 84 hour (n= 113, 107, 75, 75) | 2.19 score on a scale | Standard Deviation 1.799 |
| 3% Menthol | PID at Rest | PID at 96 hour (n= 112, 107, 75, 74) | 2.23 score on a scale | Standard Deviation 1.721 |
| 3% Menthol | PID at Rest | PID at 108 hour (n=112, 107, 75, 74) | 2.48 score on a scale | Standard Deviation 1.743 |
| 3% Menthol | PID at Rest | PID at 120 hour (n= 111, 107, 74, 74) | 2.30 score on a scale | Standard Deviation 1.856 |
| 3% Menthol | PID at Rest | PID at 132 hour (n= 110, 107, 74, 74) | 2.68 score on a scale | Standard Deviation 1.873 |
| 3% Menthol | PID at Rest | PID at 144 hour (n= 110, 107, 74, 74) | 2.59 score on a scale | Standard Deviation 1.965 |
| 3% Menthol | PID at Rest | PID at 156 hour (n= 109, 107, 74, 74) | 2.77 score on a scale | Standard Deviation 1.884 |
| 3% Menthol | PID at Rest | PID at 168 hour (n= 105, 104, 73, 74) | 2.75 score on a scale | Standard Deviation 1.869 |
| 3% Menthol | PID at Rest | PID at 180 hour (n= 105, 104, 73, 72) | 2.95 score on a scale | Standard Deviation 1.747 |
| 3% Menthol | PID at Rest | PID at 192 hour (n= 101, 102, 71, 72) | 2.90 score on a scale | Standard Deviation 1.928 |
| 3% Menthol | PID at Rest | PID at 216 hour (n= 95, 100, 69, 72) | 3.22 score on a scale | Standard Deviation 2.306 |
| 3% Menthol | PID at Rest | PID at 228 hour (n= 95, 100, 69, 72) | 3.64 score on a scale | Standard Deviation 2 |
| 3% Menthol | PID at Rest | PID at 240 hour (n= 32, 43, 22, 42) | 3.36 score on a scale | Standard Deviation 2.61 |
| Placebo | PID at Rest | PID at 84 hour (n= 113, 107, 75, 75) | 2.03 score on a scale | Standard Deviation 1.931 |
| Placebo | PID at Rest | PID at 240 hour (n= 32, 43, 22, 42) | 3.67 score on a scale | Standard Deviation 2.149 |
| Placebo | PID at Rest | PID at 168 hour (n= 105, 104, 73, 74) | 2.64 score on a scale | Standard Deviation 2.004 |
| Placebo | PID at Rest | PID at 72 hour (n= 117, 112, 77, 75) | 1.76 score on a scale | Standard Deviation 1.972 |
| Placebo | PID at Rest | PID at 60 hour (n= 117, 112, 77, 75) | 1.64 score on a scale | Standard Deviation 1.893 |
| Placebo | PID at Rest | PID at 228 hour (n= 95, 100, 69, 72) | 3.53 score on a scale | Standard Deviation 2.083 |
| Placebo | PID at Rest | PID at 180 hour (n= 105, 104, 73, 72) | 2.88 score on a scale | Standard Deviation 2.103 |
| Placebo | PID at Rest | PID at 48 hour (n=117, 112, 77, 75) | 1.45 score on a scale | Standard Deviation 1.84 |
| Placebo | PID at Rest | PID at 36 hour (n= 117, 112, 77, 75) | 1.09 score on a scale | Standard Deviation 1.787 |
| Placebo | PID at Rest | PID at 10 min. (n=117, 112, 77, 75) | 0.25 score on a scale | Standard Deviation 1.175 |
| Placebo | PID at Rest | PID at 192 hour (n= 101, 102, 71, 72) | 3.00 score on a scale | Standard Deviation 2.035 |
| Placebo | PID at Rest | PID at 24 hour (n= 117, 112, 77, 75) | 1.13 score on a scale | Standard Deviation 1.711 |
| Placebo | PID at Rest | PID at 18 hour (n= 117, 112, 77, 75) | 0.85 score on a scale | Standard Deviation 1.666 |
| Placebo | PID at Rest | PID at 12 hour (n= 117, 112, 77, 75) | 0.68 score on a scale | Standard Deviation 1.535 |
| Placebo | PID at Rest | PID at 204 hour (n= 101, 100, 71, 72) | 3.21 score on a scale | Standard Deviation 2.021 |
| Placebo | PID at Rest | PID at 6 hour (n= 117, 112, 77, 75) | 0.53 score on a scale | Standard Deviation 1.554 |
| Placebo | PID at Rest | PID at 4 hour (n=117, 112, 77, 75) | 0.43 score on a scale | Standard Deviation 1.678 |
| Placebo | PID at Rest | PI at Baseline (n=117, 112, 77, 75) | 7.7 score on a scale | Standard Deviation 1.47 |
| Placebo | PID at Rest | PID at 216 hour (n= 95, 100, 69, 72) | 3.26 score on a scale | Standard Deviation 1.936 |
| Placebo | PID at Rest | PID at 132 hour (n= 110, 107, 74, 74) | 2.49 score on a scale | Standard Deviation 1.967 |
| Placebo | PID at Rest | PID at 1 hour (n=117, 112, 77, 75) | 0.41 score on a scale | Standard Deviation 1.62 |
| Placebo | PID at Rest | PID at 144 hour (n= 110, 107, 74, 74) | 2.49 score on a scale | Standard Deviation 1.918 |
| Placebo | PID at Rest | PID at 120 hour (n= 111, 107, 74, 74) | 2.09 score on a scale | Standard Deviation 1.917 |
| Placebo | PID at Rest | PID at 108 hour (n=112, 107, 75, 74) | 2.27 score on a scale | Standard Deviation 1.889 |
| Placebo | PID at Rest | PID at 30 min. (n=117, 112, 77, 75) | 0.44 score on a scale | Standard Deviation 1.328 |
| Placebo | PID at Rest | PID at 156 hour (n= 109, 107, 74, 74) | 2.65 score on a scale | Standard Deviation 2.129 |
| Placebo | PID at Rest | PID at 96 hour (n= 112, 107, 75, 74) | 2.00 score on a scale | Standard Deviation 1.72 |
Secondary
Skin Temperature
Skin temperature was measured by thermal imaging.
Time frame: At 10, 30, 60 minutes, 4 and 6 hours
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Skin Temperature | At 240 min. | 30.52 degree celsius (°C) | Standard Deviation 2.88 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Skin Temperature | At 30 min. | 28.26 degree celsius (°C) | Standard Deviation 3.161 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Skin Temperature | At 360 min. | 31.02 degree celsius (°C) | Standard Deviation 2.951 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Skin Temperature | At 60 min. | 28.64 degree celsius (°C) | Standard Deviation 2.986 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Skin Temperature | At 10 min. | 27.69 degree celsius (°C) | Standard Deviation 3.706 |
| Placebo | Skin Temperature | At 60 min. | 30.74 degree celsius (°C) | Standard Deviation 2.781 |
| Placebo | Skin Temperature | At 240 min. | 31.26 degree celsius (°C) | Standard Deviation 2.981 |
| Placebo | Skin Temperature | At 360 min. | 31.53 degree celsius (°C) | Standard Deviation 3.299 |
| Placebo | Skin Temperature | At 30 min. | 29.81 degree celsius (°C) | Standard Deviation 2.595 |
| Placebo | Skin Temperature | At 10 min. | 29.31 degree celsius (°C) | Standard Deviation 2.61 |
| 3% Menthol | Skin Temperature | At 60 min. | 30.22 degree celsius (°C) | Standard Deviation 2.388 |
| 3% Menthol | Skin Temperature | At 10 min. | 29.92 degree celsius (°C) | Standard Deviation 2.118 |
| 3% Menthol | Skin Temperature | At 30 min. | 30.50 degree celsius (°C) | Standard Deviation 2.117 |
| 3% Menthol | Skin Temperature | At 240 min. | 31.15 degree celsius (°C) | Standard Deviation 3.221 |
| 3% Menthol | Skin Temperature | At 360 min. | 31.27 degree celsius (°C) | Standard Deviation 3.925 |
| Placebo | Skin Temperature | At 240 min. | 31.57 degree celsius (°C) | Standard Deviation 2.7 |
| Placebo | Skin Temperature | At 30 min. | 31.47 degree celsius (°C) | Standard Deviation 3.386 |
| Placebo | Skin Temperature | At 10 min. | 30.93 degree celsius (°C) | Standard Deviation 2.842 |
| Placebo | Skin Temperature | At 60 min. | 31.78 degree celsius (°C) | Standard Deviation 3.213 |
| Placebo | Skin Temperature | At 360 min. | 32.07 degree celsius (°C) | Standard Deviation 3.482 |
Secondary
Sum of Pain Intensity Difference (SPID)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 1 to 3 days | 101.54 score on a scale | Standard Deviation 87.184 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0-12 hours | 9.19 score on a scale | Standard Deviation 18.788 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0 to 7 days | 451.12 score on a scale | Standard Deviation 265.919 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0-1 days | 26.01 score on a scale | Standard Deviation 38.722 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0-6 hours | 4.16 score on a scale | Standard Deviation 9.299 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0-1 days | 26.54 score on a scale | Standard Deviation 28.497 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 1 to 3 days | 100.07 score on a scale | Standard Deviation 71.085 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0 to 7 days | 452.44 score on a scale | Standard Deviation 244.488 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0-12 hours | 9.13 score on a scale | Standard Deviation 13.284 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0-6 hours | 3.19 score on a scale | Standard Deviation 5.862 |
| 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0-1 days | 30.91 score on a scale | Standard Deviation 34.158 |
| 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0-6 hours | 4.72 score on a scale | Standard Deviation 6.306 |
| 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0-12 hours | 11.74 score on a scale | Standard Deviation 14.675 |
| 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 1 to 3 days | 104.26 score on a scale | Standard Deviation 83.689 |
| 3% Menthol | Sum of Pain Intensity Difference (SPID) | At 0 to 7 days | 464.96 score on a scale | Standard Deviation 281.243 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 1 to 3 days | 90.88 score on a scale | Standard Deviation 82.626 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0-12 hours | 10.05 score on a scale | Standard Deviation 16.706 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0-6 hours | 4.37 score on a scale | Standard Deviation 8.287 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0-1 days | 26.21 score on a scale | Standard Deviation 34.877 |
| Placebo | Sum of Pain Intensity Difference (SPID) | At 0 to 7 days | 438.45 score on a scale | Standard Deviation 287.369 |
Secondary
Time of Onset of Cooling Sensation (TOCS)
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Time of Onset of Cooling Sensation (TOCS) | 0.17 Hours |
| Placebo | Time of Onset of Cooling Sensation (TOCS) | 0.17 Hours |
| 3% Menthol | Time of Onset of Cooling Sensation (TOCS) | 0.17 Hours |
| Placebo | Time of Onset of Cooling Sensation (TOCS) | 0.17 Hours |
p-value: 0.700395% CI: [0.79, 1.43]chi-square test of survival analysis
p-value: 0.956595% CI: [0.75, 1.35]chi-square test of survival analysis
p-value: 0.621695% CI: [0.82, 1.4]chi-square test of survival analysis
Secondary
Time of Onset of Meaningful Pain Relief (TOMR)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Time of Onset of Meaningful Pain Relief (TOMR) | 92.50 Hours |
| Placebo | Time of Onset of Meaningful Pain Relief (TOMR) | 76.83 Hours |
| 3% Menthol | Time of Onset of Meaningful Pain Relief (TOMR) | 72.00 Hours |
| Placebo | Time of Onset of Meaningful Pain Relief (TOMR) | 93.50 Hours |
p-value: 0.981795% CI: [0.74, 1.37]chi-square test of survival analysis
p-value: 0.691895% CI: [0.67, 1.31]chi-square test of survival analysis
p-value: 0.238995% CI: [0.87, 1.73]chi-square test of survival analysis
Secondary
Time of Onset of Pain Relief (TOPR)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Time of Onset of Pain Relief (TOPR) | 1.03 Hours |
| Placebo | Time of Onset of Pain Relief (TOPR) | 4.00 Hours |
| 3% Menthol | Time of Onset of Pain Relief (TOPR) | 1.00 Hours |
| Placebo | Time of Onset of Pain Relief (TOPR) | 4.00 Hours |
p-value: 0.540495% CI: [0.81, 1.48]chi-square test of survival analysis
p-value: 0.463995% CI: [0.67, 1.2]chi-square test of survival analysis
p-value: 0.511895% CI: [0.84, 1.43]chi-square test of survival analysis
Secondary
Time to Complete Recovery
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Time to Complete Recovery | 240.00 Hours |
| Placebo | Time to Complete Recovery | 240.00 Hours |
| 3% Menthol | Time to Complete Recovery | 240.00 Hours |
| Placebo | Time to Complete Recovery | 240.00 Hours |
p-value: 0.040895% CI: [1.04, 5.7]chi-square test of survival analysis
p-value: 0.450795% CI: [0.65, 2.65]chi-square test of survival analysis
p-value: 0.31595% CI: [0.73, 2.61]chi-square test of survival analysis
Secondary
Total Pain Relief (TOTPAR)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Total Pain Relief (TOTPAR) | 0-6 hours | 2.81 PRS Score (0 - 4 scale) | Standard Deviation 3.162 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Total Pain Relief (TOTPAR) | 0-12 hours | 6.86 PRS Score (0 - 4 scale) | Standard Deviation 6.125 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Total Pain Relief (TOTPAR) | 0- 24 hours | 16.04 PRS Score (0 - 4 scale) | Standard Deviation 12.048 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Total Pain Relief (TOTPAR) | 0-72 hours | 60.14 PRS Score (0 - 4 scale) | Standard Deviation 37.867 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Total Pain Relief (TOTPAR) | 24-72 hours | 44.10 PRS Score (0 - 4 scale) | Standard Deviation 29.344 |
| 1% Diclofenac Sodium Plus (+) 3% Menthol | Total Pain Relief (TOTPAR) | 0-168 hours | 172.97 PRS Score (0 - 4 scale) | Standard Deviation 98.838 |
| Placebo | Total Pain Relief (TOTPAR) | 0-168 hours | 170.73 PRS Score (0 - 4 scale) | Standard Deviation 97.187 |
| Placebo | Total Pain Relief (TOTPAR) | 0-72 hours | 61.24 PRS Score (0 - 4 scale) | Standard Deviation 35.877 |
| Placebo | Total Pain Relief (TOTPAR) | 0-6 hours | 2.64 PRS Score (0 - 4 scale) | Standard Deviation 2.902 |
| Placebo | Total Pain Relief (TOTPAR) | 0- 24 hours | 16.14 PRS Score (0 - 4 scale) | Standard Deviation 12.479 |
| Placebo | Total Pain Relief (TOTPAR) | 0-12 hours | 6.81 PRS Score (0 - 4 scale) | Standard Deviation 6.178 |
| Placebo | Total Pain Relief (TOTPAR) | 24-72 hours | 45.11 PRS Score (0 - 4 scale) | Standard Deviation 26.431 |
| 3% Menthol | Total Pain Relief (TOTPAR) | 0-12 hours | 8.02 PRS Score (0 - 4 scale) | Standard Deviation 7.045 |
| 3% Menthol | Total Pain Relief (TOTPAR) | 0- 24 hours | 18.85 PRS Score (0 - 4 scale) | Standard Deviation 14.517 |
| 3% Menthol | Total Pain Relief (TOTPAR) | 0-72 hours | 66.69 PRS Score (0 - 4 scale) | Standard Deviation 40.36 |
| 3% Menthol | Total Pain Relief (TOTPAR) | 0-168 hours | 184.17 PRS Score (0 - 4 scale) | Standard Deviation 102.787 |
| 3% Menthol | Total Pain Relief (TOTPAR) | 24-72 hours | 47.84 PRS Score (0 - 4 scale) | Standard Deviation 29.102 |
| 3% Menthol | Total Pain Relief (TOTPAR) | 0-6 hours | 3.27 PRS Score (0 - 4 scale) | Standard Deviation 3.176 |
| Placebo | Total Pain Relief (TOTPAR) | 24-72 hours | 43.04 PRS Score (0 - 4 scale) | Standard Deviation 31.57 |
| Placebo | Total Pain Relief (TOTPAR) | 0-168 hours | 174.00 PRS Score (0 - 4 scale) | Standard Deviation 94.917 |
| Placebo | Total Pain Relief (TOTPAR) | 0-12 hours | 6.35 PRS Score (0 - 4 scale) | Standard Deviation 6.732 |
| Placebo | Total Pain Relief (TOTPAR) | 0-72 hours | 58.75 PRS Score (0 - 4 scale) | Standard Deviation 41.724 |
| Placebo | Total Pain Relief (TOTPAR) | 0-6 hours | 2.75 PRS Score (0 - 4 scale) | Standard Deviation 3.184 |
| Placebo | Total Pain Relief (TOTPAR) | 0- 24 hours | 15.71 PRS Score (0 - 4 scale) | Standard Deviation 13.146 |