PainPhase 3NCT02100670
A Multicenter Efficacy Study of a Diclofenac+Menthol Gel in Subjects With Ankle Sprain
A Phase 3 study testing 1% diclofenac sodium plus 3% menthol, 1% diclofenac sodium plus 0.09% menthol and 3% menthol in people with Pain, run by GlaxoSmithKline at 3 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Pain
- What is being tested?
- 1% diclofenac sodium plus 3% menthol, 1% diclofenac sodium plus 0.09% menthol and 3% menthol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 385 participants
- Where
- 3 sitesGermany
- Study dates
- 1 Nov 2013to 22 Mar 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
PAREXEL International - Sites in Germany
Berlin, D-14050
PAREXEL International, LLC
Berlin, D-14050
pro scientia med im MARE Klinikum
Kiel, 24119
About this study
Official title: A Clinical Study to Assess the Efficacy and Onset of Pain Relief of Topical MFC51123 Diclofenac-Menthol Gel Versus Controls in Ankle Sprain
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.
Read the 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.
- Conditions
- Pain
- Being tested
- 1% diclofenac sodium plus 3% menthol, 1% diclofenac sodium plus 0.09% menthol, 3% menthol, Placebo with 0.09% menthol gel
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1% diclofenac sodium plus 3% mentholDrug
To be applied four times daily for 10 days.
1% diclofenac sodium plus 0.09% mentholDrug
To be applied four times daily for 10 days.
3% mentholDrug
To be applied four times daily for 10 days.
Placebo with 0.09% menthol gelDrug
To be applied four times daily for 10 days.
| Study group | Role | What they receive |
|---|---|---|
| 1% diclofenac sodium plus 3% menthol | Experimental | 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. Receives: Drug: 1% diclofenac sodium plus 3% menthol |
| 1% diclofenac sodium plus 0.09% menthol | Experimental | 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. Receives: Drug: 1% diclofenac sodium plus 0.09% menthol |
| 3% menthol | Experimental | 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. Receives: Drug: 3% menthol |
| Placebo with 0.09% menthol gel | Placebo comparator | 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. Receives: Drug: Placebo with 0.09% menthol gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 72 hours
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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'.
Measured: 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
Measured: 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?
Measured: 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.
Measured: Baseline to 168 hours
Skin Temperature
Skin temperature was measured by thermal imaging.
Measured: At 10, 30, 60 minutes, 4 and 6 hours
Ankle Swelling
Ankle swelling measured by "figure of eight" method of injured ankle.
Measured: 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).
Measured: 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)
Measured: up to Day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2014 (estimated)
- Study start1 Nov 2013
- Primary completion1 Mar 2015
- Study completion22 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 385 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100670
- Sponsor's protocol ID
- 202179
- Other IDs
- RH01805
- Status last verified
- May 2017
- First submitted
- 27 Mar 2014
- Last updated
- 12 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 28345425
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study to Assess the Efficacy and Onset of Pain Relief of Topical MFC51123 Diclofenac-Menthol Gel Versus Controls in Ankle Sprain
- ClinicalTrials.gov ID
- NCT02100670
- Acronym / sponsor ID
- 202179
- Conditions
- Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 385 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2013
- Primary completion
- 1 Mar 2015 (actual)
- Study completion
- 22 Mar 2015 (actual)
- First posted
- 1 Apr 2014 (estimated)
- Results
- Posted 12 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1% diclofenac sodium plus 3% menthol | Experimental | Drug: 1% diclofenac sodium plus 3% menthol1% 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. |
| 1% diclofenac sodium plus 0.09% menthol | Experimental | Drug: 1% diclofenac sodium plus 0.09% menthol1% 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. |
| 3% menthol | Experimental | Drug: 3% menthol3% 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. |
| Placebo with 0.09% menthol gel | Placebo comparator | Drug: Placebo with 0.09% menthol gelPlacebo 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. |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1% diclofenac sodium plus 3% mentholTo be applied four times daily for 10 days. | Drug | 1% diclofenac sodium plus 3% menthol |
| 1% diclofenac sodium plus 0.09% mentholTo be applied four times daily for 10 days. | Drug | 1% diclofenac sodium plus 0.09% menthol |
| 3% mentholTo be applied four times daily for 10 days. | Drug | 3% menthol |
| Placebo with 0.09% menthol gelTo be applied four times daily for 10 days. | Drug | Placebo with 0.09% menthol gel |
Primary outcome
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.
13 secondary outcomes
AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo
Time frame: up to 72 hours
Pain Intensity Difference (PID) on Movement
Time frame: Baseline to 10 days
PID at Rest
Time frame: Baseline to 10 days
Pain Relief Score (PRS)
Time frame: Day 1 to Day 7
Sum of Pain Intensity Difference (SPID)
Time frame: Baseline to Day 7
Time of Onset of Pain Relief (TOPR)
Time frame: Baseline to 10 days (end of study)
Time of Onset of Meaningful Pain Relief (TOMR)
Time frame: up to 10 days (end of study)
Time of Onset of Cooling Sensation (TOCS)
Time frame: up to 6 hours
Total Pain Relief (TOTPAR)
Time frame: Baseline to 168 hours
Skin Temperature
Time frame: At 10, 30, 60 minutes, 4 and 6 hours
Ankle Swelling
Time frame: Day 1 (baseline), 3, and 7
Time to Complete Recovery
Time frame: up to 240 hours
Patient's Global Assessment in Response to Treatment (PGART)
Time frame: up to Day 10
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28345425Lai 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 1% diclofenac sodium plus 3% menthol, 1% diclofenac sodium plus 0.09% menthol and 3% menthol in people with Pain, run by GlaxoSmithKline at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02100670, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2018.