Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02100670
Recruitment Status : Completed
First Posted : April 1, 2014
Results First Posted : January 12, 2018
Last Update Posted : January 12, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE March 27, 2014
First Posted Date  ICMJE April 1, 2014
Results First Submitted Date  ICMJE June 2, 2016
Results First Posted Date  ICMJE January 12, 2018
Last Update Posted Date January 12, 2018
Study Start Date  ICMJE November 1, 2013
Actual Primary Completion Date March 1, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 11, 2018)
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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 27, 2014)
  • AUC (1-3 days) [ Time Frame: Baseline to 72 hours ]
    AUC of pain intensity (PI) on movement measured by a numerical rating scale (NRS) during the 48 hour time interval from Day 1 to 3. AUC1-3 day will be calculated based on trapezoidal method. Pain intensity will be measured in NRS scale from 0 (no pain) to 10 (extreme pain). Subject will assess 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.
  • Pain Intensity Difference (PID) on movement [ Time Frame: Baseline to 10 days ]
    PID on movement (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. Subject will assess 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.
  • PID at rest [ Time Frame: Baseline to 10 days ]
    PID at rest will be calculated as PI at a given time 't' at rest subtracted by the PI at baseline measured using NRS scale. Subject will assess 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.
  • Pain Relief Score (PRS) [ Time Frame: Baseline to Day 10 ]
    Pain relief will be 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 will assess 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) [ Time Frame: Baseline to Day 7 ]
    SPID will be measured 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.
  • Time of Onset of Pain Relief (TOPR) [ Time Frame: Baseline to Day 3 ]
    TOPR will be measured by time when subjects reported PRS ≥ 1, i.e. a "little" or "perceptible" pain relief'.
  • Time of Onset of Meaningful Pain Relief (TOMR) [ Time Frame: Baseline to Day 4 ]
    TOMR will be measured by time when subjects reported PRS ≥ 2, i.e. "some" or "meaningful" pain relief
  • Time of Onset of Cooling Sensation (TOCS) [ Time Frame: Baseline 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, subjects will be 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?
  • Total Pain Relief (TOTPAR) [ Time Frame: Baseline to Days 2, 3, and 7 ]
    TOTPAR will be calculated as sum of the products of PRS with time interval from one time point to the other.
  • Skin Temperature [ Time Frame: Baseline to 10, 30, 60 minutes, and 4 and 6 hours ]
    Skin temperature will be measured by thermal imaging.
  • Ankle Swelling [ Time Frame: Baseline to Days 1, 3, and 7 ]
    Reduction in ankle swelling as change from baseline measured by "figure of eight" method of injured ankle measurement
  • Time to complete Recovery [ Time Frame: Baseline to Day 10 ]
    Time to complete recovery 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)
  • Patient's Global Assessment in Response to Treatment (PGART) [ Time Frame: Baseline to Day 10 ]
    PGART will be measured at the end of study in a scale from 0-4 (Where: 0- Poor; 1- Fair; 2- Good; 3- Very Good; 4- Excellent)
Change History Complete list of historical versions of study NCT02100670 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2018)
  • AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo [ Time Frame: 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.
  • Pain Intensity Difference (PID) on Movement [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: up to 10 days (end of study) ]
    TOMR was measured by time when participants reported PRS ≥ 2, i.e. "some" or "meaningful" pain relief
  • Time of Onset of Cooling Sensation (TOCS) [ Time Frame: 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?
  • Total Pain Relief (TOTPAR) [ Time Frame: 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 [ Time Frame: At 10, 30, 60 minutes, 4 and 6 hours ]
    Skin temperature was measured by thermal imaging.
  • Ankle Swelling [ Time Frame: Day 1 (baseline), 3, and 7 ]
    Ankle swelling measured by "figure of eight" method of injured ankle.
  • Time to Complete Recovery [ Time Frame: 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) [ Time Frame: 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2014)
Adverse events (AEs) [ Time Frame: Approximately 3 weeks ]
Frequency and intensity of AEs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multicenter Efficacy Study of a Diclofenac+Menthol Gel in Subjects With Ankle Sprain
Official Title  ICMJE A Clinical Study to Assess the Efficacy and Onset of Pain Relief of Topical MFC51123 Diclofenac-Menthol Gel Versus Controls in Ankle Sprain
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Pain
Intervention  ICMJE
  • Drug: 1% diclofenac sodium plus 3% menthol
    To be applied four times daily for 10 days.
  • Drug: 1% diclofenac sodium plus 0.09% menthol
    To be applied four times daily for 10 days.
  • Drug: 3% menthol
    To be applied four times daily for 10 days.
  • Drug: Placebo with 0.09% menthol gel
    To be applied four times daily for 10 days.
Study Arms  ICMJE
  • Experimental: 1% diclofenac sodium plus 3% menthol
    1% diclofenac sodium plus 3% menthol gel supplied in 30 gram (g) tubes sufficient for each subject to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
    Intervention: Drug: 1% diclofenac sodium plus 3% menthol
  • Experimental: 1% diclofenac sodium plus 0.09% menthol
    1% diclofenac sodium plus 0.09% menthol gel supplied in 30g tubes sufficient for each subject to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
    Intervention: Drug: 1% diclofenac sodium plus 0.09% menthol
  • Experimental: 3% menthol
    3% menthol gel supplied in 30g tubes sufficient for each subject to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
    Intervention: Drug: 3% menthol
  • Placebo Comparator: Placebo with 0.09% menthol gel
    Placebo with 0.09% menthol gel supplied in 30g tubes sufficient for each subject to apply 4g of gel to the injured ankle region four times daily for up to 10 days.
    Intervention: Drug: Placebo with 0.09% menthol gel
Publications * Lai PM, Collaku A, Reed K. Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial. J Int Med Res. 2017 Apr;45(2):647-661. doi: 10.1177/0300060517700322. Epub 2017 Mar 27.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2015)
385
Original Estimated Enrollment  ICMJE
 (submitted: March 27, 2014)
400
Actual Study Completion Date  ICMJE March 22, 2015
Actual Primary Completion Date March 1, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02100670
Other Study ID Numbers  ICMJE 202179
RH01805 ( Other Identifier: GSK )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP