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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
385
To be applied four times daily for 10 days.
To be applied four times daily for 10 days.
To be applied four times daily for 10 days.
PAREXEL International - Sites in Germany
Berlin, Germany
PAREXEL International, LLC
Berlin, Germany
pro scientia med im MARE Klinikum
Kiel, Germany
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
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
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
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.
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To be applied four times daily for 10 days.
Time frame: Baseline to 10 days
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
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
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)
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)
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
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
Skin Temperature
Skin temperature was measured by thermal imaging.
Time frame: At 10, 30, 60 minutes, 4 and 6 hours
Ankle Swelling
Ankle swelling measured by "figure of eight" method of injured ankle.
Time frame: Day 1 (baseline), 3, and 7
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
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