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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Teikoku Seiyaku Co. Ltd.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

6 Mar 2025 → 30 Oct 2025

Decision date (initial)

2024-10-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Teikoku Seiyaku Co Ltd.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate that the EFTS is superior in pain reduction compared to a matching placebo in patients with acute ankle sprains based on Sum of Pain Intensity Difference (SPID) of Visual Analogue Scale (VAS) score on pain-on-movement (POM) over 0-48 hours.

Secondary objectives 4

1. To demonstrate that the EFTS is superior in pain reduction compared to a matching placebo in patients with acute ankle sprains based on pain-on-movement (POM) and pain-at-rest (PAR) assessments and derived variables as well as global efficacy assessments during the 7-day observation period.
2. Characterization of tolerability during treatment
3. Characterization of local tolerability during treatment
4. Characterization of adhesion

Conditions and MedDRA coding

Acute ankle sprains grade I

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. acute ankle sprains Grade I
2. location of injury such that pain-on-movement (POM) is elicited on active standardized movement
3. enrollment within 6 hours of the injury
4. baseline VAS score for POM of injured extremity > 50 mm on a 100 mm VAS
5. adult male or female patients
6. age 18 to 64 years (including)
7. having given written informed consent
8. satisfactory health as determined by the Investigator based on medical history and physical examination.

Exclusion criteria 22

1. 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
2. pregnant and lactating women
3. women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) who are not using an acceptable method of contraception (as defined in the clinical trial protocol)
4. known hypersensitivity to Esflurbiprofen, R-flurbiprofen or one of the excipients of the patch
5. patients with any ongoing condition that may interfere with the absorption, distribution, metabolism, or excretion of Esflurbiprofen
6. history of previous significant injury to the same extremity within 6 months
7. patients with a disease affecting the same limb, such as synovitis, rheumatoid arthritis, arthrosis, etc.
8. patients having an ongoing painful condition associated with blunt injury/contusion
9. patients suffering from symptoms of an infectious disease including swelling of any joint of the affected lower limbs
10. patients who had surgery of the affected lower limb within one year of study entry
11. 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).
12. excessively hairy skin at application site, cutting the hair in the injured site prior to patch application will qualify for inclusion
13. patients with a blood coagulation disorder
14. patients who use any impermissible medication
15. current skin disorder or shaving hair at application site
16. history of excessive sweating/hyperhidrosis inclusive of application site
17. intake of NSAIDs or analgesics within 36 hours, opioids within 7 days, or systemic corticosteroids (except inhaled corticosteroids for e.g. topical treatment of bronchial asthma) within 60 days of inclusion in the study
18. intake of long-acting NSAIDs or application of topical medication since the injury (RICE allowed)
19. participation in a clinical study within 30 days before inclusion in the study or concomitantly
20. participation in this clinical study in another center
21. drug or alcohol abuse in the opinion of the Investigator
22. known allergy to paracetamol and galenic components of the rescue medication

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Sum of Pain Intensity Difference (SPID), of 100-mm- Visual Analogue Scale (VAS) score on pain-on-movement (POM) over 0-48 hours

Secondary endpoints 15

1. VAS score on POM at 6 h, before bed time on Day 1, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 h and related PIDs and SPIDs
2. VAS score on PAR at 6 h, before bed time on Day 1, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 h and related PIDs and SPIDs
3. Time to meaningful/optimal reduction of pain defined as first at least 30% (meaningful) and 50% (optimal) reduction from baseline of VAS on POM
4. Time to complete resolution of pain-on-movement defined as POM VAS value of 0 mm
5. Time to complete resolution of pain-at-rest defined as PAR VAS value of 0 mm.
6. Responder rate 1 (defined as the number of patients achieving at least 50% reduction from baseline in the VAS score for POM at 48 hours)
7. Responder rate 2 (defined as the number of patients able to resume training / normal physical activity by 168 hours)
8. Resolution of ankle sprain (defined as the percentage of patients who showed POM=PAR=0 at 168 hours)
9. Global efficacy assessments by physician (GEA, 5-point scale: 0=no response; 1=poor response; 2=fair response; 3=good response; 4=excellent response) at 48, 72 and 168 hours
10. Global efficacy assessments by patient (GEA, 5-point scale: 0=no response; 1=poor response; 2=fair response; 3=good response; 4=excellent response) at 48, 72 and 168 hours
11. Use of rescue medication at every visit except Visit 1
12. AEs and SAEs
13. Local tolerability (skin damage/reaction according to an 8-point scale) at Visit 6
14. 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) at Visit 2-5 (24 hours after EFTS application).
15. Adhesive power of the EFTS will be visually assessed and classified by the subject 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) at before/after bed time and 24 hours after each EFTS application

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Teikoku Seiyaku Co. Ltd.

Sponsor organisation

Teikoku Seiyaku Co. Ltd.

Address

567 Sanbonmatsu

City

Higashikagawa

Postcode

769-2695

Country

Japan

Scientific contact point

Organisation

Teikoku Seiyaku Co. Ltd.

Contact name

Director, Regulatory Strategy & Intelligence

Public contact point

Organisation

Teikoku Seiyaku Co. Ltd.

Contact name

Director, Regulatory Strategy & Intelligence

Third parties 4

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications