Ankle SprainsPhase 3NCT06866613
Phase III Trial to Evaluate the Efficacy and Safety in Patients With Ankle Sprains.
A Phase 3 study testing Esflurbiprofen Topical System (EFTS) in people with Ankle Sprains, run by Teikoku Seiyaku Co., Ltd. at 5 sites in Germany.
Trial summary
This study is a multi-center, double-blind, randomized controlled trial to evaluate the efficacy and safety of EFTS vs. placebo in patients with ankle sprains. The primary objective of this study is to demonstrate that the EFTS is superior in pain reduction compared to a matching placebo in patients with ankle… Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Ankle Sprains
- What is being tested?
- Esflurbiprofen Topical System (EFTS)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 5 sitesGermany
- Study dates
- 31 Mar 2025to 30 Oct 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- acute ankle sprains Grade I
- location of injury such that pain-on-movement (POM) is elicited on active standardized movement
- enrollment within 6 hours of the injury
- baseline VAS score for POM of injured extremity > 50 mm on a 100 mm VAS
- adult male or female patients
- age 18 to 64 years (including)
- having given written informed consent
- satisfactory health as determined by the Investigator based on medical history and physical examination.
Who cannot join
- significant concomitant injury in association with the index soft- tissue injury/contusion or strain; e.g. fracture, nerve injury, ligament disruption, tear of muscle or cartilage, or open wound
- current skin disorder or shaving hair at application site
- history of excessive sweating/hyperhidrosis inclusive of application site
- intake of non-steroidal anti-inflammatory drags (NSAIDs) or analgesics within 36 hours, opioids within 7 days, or corticosteroids (except inhaled corticosteroids for e.g. topical treatment of bronchial asthma) within 60 days of inclusion in the study
- intake of long-acting NSAIDs or application of topical medication since the injury (Rest, Ice, Compression, and elevation (RICE) allowed)
- participation in a clinical study within 30 days before inclusion in the study or concomitantly
Show all 26Show fewer
- participation in this clinical study in another center
- drug or alcohol abuse in the opinion of the Investigator
- pregnant and lactating women
- women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) who are not using an acceptable method of contraception defined as:
- Surgical sterilization
- Combined (estrogen and progestogen containing) hormonal contraception, e.g., oral, intravaginal, transdermal and progestogen-only hormonal contraception e.g. oral, injectable, implantable as well as intrauterine device (IUD) and intrauterine hormone-releasing system (IUS) each in combination with male condom to increase safety effect (double barrier method)
- Total abstinence throughout the study at the discretion of the Investigator
- Periodic abstinence is NOT an acceptable method of contraception. An acceptable method of contraception must be maintained throughout the study
- A woman who is post-menopausal must have a negative urine pregnancy test at screening but will not need to comply with an acceptable method of contraception. Women are considered post-menopausal and not of child bearing potential if they had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of sterilisation, salpingectomy) or 6 months of spontaneous amenorrhea with serum Follic simulating hormone (FSH) levels > 40 mIU/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- known hypersensitivity to Esflurbiprofen, R-flurbiprofen or one of the excipients of the patch
- patients with any ongoing condition that may interfere with the absorption, distribution, metabolism, or excretion of Esflurbiprofen
- history of previous significant injury to the same extremity within 6 months
- patients with a disease affecting the same limb, such as synovitis, rheumatoid arthritis, arthrosis, etc.
- patients having an ongoing painful condition associated with blunt injury/contusion
- patients suffering from symptoms of an infectious disease including swelling of any joint of the affected lower limbs
- patients who had surgery of the affected lower limb within one year of study entry
- patients with significant diseases (defined as a disease which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study; includes patients with a history of gastrointestinal bleeding, significant cardiovascular, liver or renal disease)
- patients with a blood coagulation disorder
- patients who use any impermissible medication
- known allergy to paracetamol and galenic components of the rescue medication
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
Medical Practice Gastl
Römerstraße, Gilching, 82205
Medical Practice Ebert
Siemensstr, Bonn, 53121
Medical Practice Prof. Predel
Siemensstr, Bonn, 53121
Medical Practice Schaale-Maas
Siemensstr, Bonn, 53121
Medical Practice Pabst
Sportschule Puch, Fürstenfeldbruck, 82556
About this study
Official title: Randomized, Controlled, Double-blind, Multi-center Trial to Evaluate the Efficacy and Safety of an Esflurbiprofen Topical System (EFTS) vs. Placebo in the Local Symptomatic and Short-term Treatment of Pain in Ankle Sprains.
This study is a multi-center, double-blind, randomized controlled trial to evaluate the efficacy and safety of EFTS vs. placebo in patients with ankle sprains. The primary objective of this study is to demonstrate that the EFTS is superior in pain reduction compared to a matching placebo in patients with ankle sprains.
The secondary objective is to evaluate tolerability, local tolerability, and adhesion of EFTS vs. placebo.
- Conditions
- Ankle Sprains
- Being tested
- Esflurbiprofen Topical System (EFTS), Placebo Patch
- Keywords
- Blunt trauma, Soft tissue injuries, sports injuries, NSAIDs, topical patch
- Medical subject headings
- Ankle Injuries, Wounds, Nonpenetrating, Soft Tissue Injuries, Athletic Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esflurbiprofen Topical System (EFTS)Drug
One EFTS is applied to the injured area over consecutive 7 days
Placebo PatchDrug
One placebo patch is applied to the injured area over consecutive 7 days
| Study group | Role | What they receive |
|---|---|---|
| TK-254RX | Experimental | Esflurbiprofen Topical System 165 mg Esflurbiprofen Receives: Drug: Esflurbiprofen Topical System (EFTS) |
| Placebo patch | Placebo comparator | Placebo patch does not contain active ingredients but it cannot be distinguished in terms of appearance, consistency, odor, and dosage form Receives: Drug: Placebo Patch |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sum of Pain Intensity Difference (SPID) on pain-on-movement (POM) over 0-48 hours
Calculating the area under the curve for the difference of each pain intensity score by 100-mm-Visual Analogue Scale (VAS) on movement from the baseline over 0-48 hours after patch application.
Measured: Day 1 to Day 3
Secondary outcomes (20)
100-mm- Visual Analogue Scale (VAS) score on pain-on-movement (POM)
VAS score from no pain (0 mm) to worst pain (100 mm) on pain-on-movement by a patient at each time point
Measured: Day 1 to Day 8
100-mm- Visual Analogue Scale (VAS) score on pain-at-rest (PAR)
VAS score from no pain (0 mm) to worst pain (100 mm) on PAR (at least 5 min rest) by a patient at each time point
Measured: Day 1 to Day 8
Sum of Pain Intensity Difference (SPID) on pain-on-movement (POM)
Calculating the area under the curve for the difference of each pain intensity score by 100-mm-Visual Analogue Scale (VAS) on movement from the baseline over day 1 to day 8.
Measured: Day 1 to Day 8
Sum of Pain Intensity Difference (SPID) on pain-at-rest (PAR)
Calculating the area under the curve for the difference of each pain intensity score by 100-mm-Visual Analogue Scale (VAS) at rest from the baseline over day 1 to day 8.
Measured: Day 1 to Day 8
Pain Intensity Difference (PID) on pain-on-movement (POM)
Difference of each pain intensity score by 100-mm-Visual Analogue Scale (VAS) on movement from the baseline at each time point.
Measured: Day 1 to Day 8
Pain Intensity Difference (PID) on pain-at-rest (PAR)
Difference of each pain intensity score by 100-mm-Visual Analogue Scale (VAS) on movement from the baseline at each time point.
Measured: Day 1 to Day 8
Time to meaningful/optimal reduction
Time to meaningful/optimal reduction of pain defined as first at least 30% (meaningful) and 50% (optimal) reduction from baseline of VAS on POM.
Measured: Day 1 to Day 8
Time to complete resolution
- Time to complete resolution of POM VAS value of 0 mm
- Time to complete resolution of PAR VAS value of 0 mm
Measured: Day 1 to Day 8
Responder rate 1
Responder rate is defined as the number of patients achieving at least 50% reduction from baseline in the VAS score for POM at 48 hours
Measured: Day 3
Responder rate 2
number of patients able to resume training / normal physical activity by 168 hours
Measured: Day 8
Resolution of ankle sprain
the percentage of patients who showed POM=PAR=0 at 168 hours
Measured: Day 8
Global efficacy assessments 1 by investigator
The global efficacy assessments are evaluated by the Investigator as the response to following questions: "Considering how this treatment has affected the patient since he/she started in the study, how well is he/she doing?" It is assessed on the following 5-point Likert scale: 0 = very good, 1 = good, 2 = fair, 3 = poor, 4 = very poor
Measured: Day 3, Day 4 and Day 8
Global efficacy assessments 2 by investigator
The global efficacy assessments are evaluated by the Investigator as the response to following questions: "How would you rate this medication for the treatment of this ankle sprain?" The evaluation is based on the following 5-point Likert scale: 0 = excellent, 1 = very good, 2 = good, 3 = moderate, 4 = poor
Measured: Day 3, Day 4 and Day 8
Global efficacy assessments 1 by patients
The global efficacy assessments are evaluated by the Investigator as the response to following questions: "Considering how this treatment has affected you since you started in the study, how well are you doing?" It is assessed on the following 5-point Likert scale: 0 = very good, 1 = good, 2 = fair, 3 = poor, 4 = very poor
Measured: Day 3, Day 4 and Day 8
Global efficacy assessments 2 by patients
The global efficacy assessments are evaluated by the patient as the response to following questions: "How do you rate this medication as a treatment for your ankle sprain?" It is assessed on the following 5-point Likert scale: 0 = excellent, 1 = very good, 2 = good, 3 = fair, 4 = poor
Measured: Day 3, Day 4 and Day 8
Number of use of rescue medication
Number of resucue medication use during clinical study
Measured: Day 1 to Day 8
Number of patients who experience adverse event and serious adverse event
Characterization of occurrence of adverse events or serious adverse events of TK-254RX or placebo patch
Measured: Day 1 to Day 8
Characterization of local tolerability
Assessing the local tolerability by using the 8-point dermal response (0: No evidence of irritation, 1: Minimal erythema, barely perceptible, 2: Definite erythema, readily visible, minimal edema or minimal papular response, 3: Erythema and papules, 4: Definite edema, 5: Erythema, edema, and papules, 6: Vesicular eruption, 7: Strong reaction spreading beyond test site) and other effects score (0: No other effect detected, A(0): Slightly glazed appearance, B(1): Markedly glazed appearance, C(2): Glazing with peeling and cracking, F(3): Glazing with fissures, G(3): Film of dried serous exudates covering all or part of the application site, H(3): Small petechial erosions and/or scabs) according to FDA recommendation
Measured: Day 8
Patch adhesion assessed by the site staff
Adhesive power of the EFTS will be visually assessed and classified by the site staff in a 5-point-score (0=≥ 90% adhered / 1= ≥75% to <90% adhered / 2=≥50% to <75% adhered / 3=>0% to <50% adhered / 4=completely detached)
Measured: Day 2 to Day 5
Patch adhesion assessed by patient
Adhesive power of the EFTS will be visually assessed and classified by a patient in a 5-point-score (0=≥ 90% adhered / 1= ≥75% to <90% adhered / 2=≥50% to <75% adhered / 3=>0% to <50% adhered / 4=completely detached)
Measured: Day 1 to Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2025
- Study start31 Mar 2025
- Primary completion18 Oct 2025
- Study completion30 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ankle SprainsStudies of the same condition, open and under way.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teikoku Seiyaku Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CRM Biometrics GmbH, SocraTec R&D GmbH, SocraMetrics GmbH, HWI pharma services GmbH, Clinsearch GmbH
- Responsible party
- Sponsor
- Investigators
- Kenichi Nishiyama, Study chair, Teikoku Seiyaku Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06866613
- Sponsor's protocol ID
- TK-254RX-0301
- Other IDs
- 2024-513063-45-00
- Status last verified
- Apr 2025
- First submitted
- 10 Feb 2025
- Last updated
- 26 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Controlled, Double-blind, Multi-center Trial to Evaluate the Efficacy and Safety of an Esflurbiprofen Topical System (EFTS) vs. Placebo in the Local Symptomatic and Short-term Treatment of Pain in Ankle Sprains.
- ClinicalTrials.gov ID
- NCT06866613
- Acronym / sponsor ID
- TK-254RX-0301
- Conditions
- Ankle Sprains
- Keywords
- Blunt trauma, Soft tissue injuries, sports injuries, NSAIDs, topical patch
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Teikoku Seiyaku Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- CRM Biometrics GmbH, SocraTec R&D GmbH, SocraMetrics GmbH, HWI pharma services GmbH, Clinsearch GmbH
- Study start
- 31 Mar 2025 (actual)
- Primary completion
- 18 Oct 2025 (actual)
- Study completion
- 30 Oct 2025 (actual)
- First posted
- 10 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multi-center, double-blind, randomized controlled trial to evaluate the efficacy and safety of EFTS vs. placebo in patients with ankle sprains. The primary objective of this study is to demonstrate that the EFTS is superior in pain reduction compared to a matching placebo in patients with ankle sprains.
The secondary objective is to evaluate tolerability, local tolerability, and adhesion of EFTS vs. placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TK-254RX | Experimental | Drug: Esflurbiprofen Topical System (EFTS)Esflurbiprofen Topical System 165 mg Esflurbiprofen |
| Placebo patch | Placebo comparator | Drug: Placebo PatchPlacebo patch does not contain active ingredients but it cannot be distinguished in terms of appearance, consistency, odor, and dosage form |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- acute ankle sprains Grade I
- location of injury such that pain-on-movement (POM) is elicited on active standardized movement
- enrollment within 6 hours of the injury
- baseline VAS score for POM of injured extremity > 50 mm on a 100 mm VAS
- adult male or female patients
Key exclusion criteria (26 listed)
- significant concomitant injury in association with the index soft- tissue injury/contusion or strain; e.g. fracture, nerve injury, ligament disruption, tear of muscle or cartilage, or open wound
- current skin disorder or shaving hair at application site
- history of excessive sweating/hyperhidrosis inclusive of application site
- intake of non-steroidal anti-inflammatory drags (NSAIDs) or analgesics within 36 hours, opioids within 7 days, or corticosteroids (except inhaled corticosteroids for e.g. topical treatment of bronchial asthma) within 60 days of inclusion in the study
- intake of long-acting NSAIDs or application of topical medication since the injury (Rest, Ice, Compression, and elevation (RICE) allowed)
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 |
|---|---|---|
| Esflurbiprofen Topical System (EFTS)One EFTS is applied to the injured area over consecutive 7 days | Drug | TK-254RX |
| Placebo PatchOne placebo patch is applied to the injured area over consecutive 7 days | Drug | Placebo patch |
Primary outcome
Sum of Pain Intensity Difference (SPID) on pain-on-movement (POM) over 0-48 hours
Time frame: Day 1 to Day 3
Calculating the area under the curve for the difference of each pain intensity score by 100-mm-Visual Analogue Scale (VAS) on movement from the baseline over 0-48 hours after patch application.
20 secondary outcomes
100-mm- Visual Analogue Scale (VAS) score on pain-on-movement (POM)
Time frame: Day 1 to Day 8
100-mm- Visual Analogue Scale (VAS) score on pain-at-rest (PAR)
Time frame: Day 1 to Day 8
Sum of Pain Intensity Difference (SPID) on pain-on-movement (POM)
Time frame: Day 1 to Day 8
Sum of Pain Intensity Difference (SPID) on pain-at-rest (PAR)
Time frame: Day 1 to Day 8
Pain Intensity Difference (PID) on pain-on-movement (POM)
Time frame: Day 1 to Day 8
Pain Intensity Difference (PID) on pain-at-rest (PAR)
Time frame: Day 1 to Day 8
Time to meaningful/optimal reduction
Time frame: Day 1 to Day 8
Time to complete resolution
Time frame: Day 1 to Day 8
Responder rate 1
Time frame: Day 3
Responder rate 2
Time frame: Day 8
Resolution of ankle sprain
Time frame: Day 8
Global efficacy assessments 1 by investigator
Time frame: Day 3, Day 4 and Day 8
Global efficacy assessments 2 by investigator
Time frame: Day 3, Day 4 and Day 8
Global efficacy assessments 1 by patients
Time frame: Day 3, Day 4 and Day 8
Global efficacy assessments 2 by patients
Time frame: Day 3, Day 4 and Day 8
Number of use of rescue medication
Time frame: Day 1 to Day 8
Number of patients who experience adverse event and serious adverse event
Time frame: Day 1 to Day 8
Characterization of local tolerability
Time frame: Day 8
Patch adhesion assessed by the site staff
Time frame: Day 2 to Day 5
Patch adhesion assessed by patient
Time frame: Day 1 to Day 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
- Individual participant dataSharing planned: No
Related trials for Ankle Sprains
Not yet recruiting
Functional Recovery After a Recent Lateral Ankle Sprain With Early Initiation of Rehabilitation: Changes in the Ankle-GO Score and Its Association With Return to Sport and Recurrent Sprains.
Ankle Sprain
Recruiting
Enovis High Ankle Sprain Brace Testing
Athletes in Cutting Sports
Recruiting
The Effects of Vestibulo-Ocular Reflex Exercises Added to Postural Stabilization Training in Amateur Athletes With Chronic Ankle Instability
Ankle Sprain, Ankle Sprain Strain
Recruiting
The Effects of Vestibulo-Ocular Reflex Exercises Added to Postural Stabilization Training in Chronic Ankle Instability
Ankle Sprains, Ankle Sprain Strain
Not yet recruiting
Collagen Scaffold Bioaugmentation for ATFL Repair in Chronic Ankle Instability
Chronic Ankle Instability, Ankle Sprain
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.
Kenichi Nishiyama study chair
Teikoku Seiyaku Co., Ltd.
5 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 Esflurbiprofen Topical System (EFTS) in people with Ankle Sprains, run by Teikoku Seiyaku Co., Ltd. at 5 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 8 inclusion and 26 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 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Sum of Pain Intensity Difference (SPID) on pain-on-movement (POM) over 0-48 hours (time frame: Day 1 to Day 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Nov 2025.