Efficacy and Safety of Esflurbiprofen Hydrogel Patch in the Treatment of Local Acute Pain

The Efficacy and Safety of an Esflurbiprofen Hydrogel Patch vs. Placebo in the Local Symptomatic and Short-term Treatment of Pain in Acute Strains, Sprains or Bruises of the Extremities Following Blunt Trauma, e.g. Sports Injuries.

Objective of this study is:

to determine efficacy and safety of a Esflurbiprofen Hydrogel Patch compared to placebo in patients with acute strains, sprains or bruises of the extremities following blunt trauma, e.g. sports injuries.

to demonstrate that the Esflurbiprofen Hydrogel Patch is superior to placebo, and that the patch has acceptable local tolerability.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Injuries; Sprains; Contusions; Strains; Bruises
• Intervention / Treatment: Drug: Esflurbiprofen Hydrogel Patch

Detailed Description

Study Design Randomized (1:1) (stratified by center and 2 subgroups), controlled, double-blind, multi-centric study in parallel groups. Patient Population/Sample size/Study Sites

The clinical trial population will consist of male or female patients, 18 - 60 years suffering from acute; strains, sprains or bruises of the extremities following blunt trauma, and meeting all clinical trial entry criteria.

200 patients will be enrolled (assumes a drop-out-rate of ≤10%).

The study will be performed in Germany in 3 sites

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • NRW
    • Cologne, NRW, Germany, 50933
      • Deutsche Sporthochschule Köln Institut für Kreislaufforschung und Sportmedizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. acute sports-related soft-tissue injury/contusion (strains, sprains, bruises) of the upper or lower limb
2. location of injury such that pain-on-movement (POM) is elicited on by specified exercises
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. size of injury, as assessed by investigator, ≥ 25 cm2 and ≤ 120 cm2
6. adult male or female patients
7. age 18 to 60 years
8. having given written informed consent
9. satisfactory health as determined by the Investigator based on medical history and physical examination.

Exclusion criteria

1. significant concomitant injury in association with the index acute sports-related soft- tissue injury/contusion; e.g. fracture, nerve injury, ligament disruption, tear of muscle or cartilage, or open wound
2. excessively hairy skin at application site, cutting the hair in the injured site prior to patch application will qualify for inclusion
3. current skin disorder or shaving hair at application site
4. history of excessive sweating/hyperhidrosis inclusive of application site
5. intake of NSAIDs or analgesics within 36 hours, opioids within 7 days, or corticosteroids within 60 days of inclusion in the study
6. intake of long-acting NSAIDs or application of topical medication since the injury (RICE allowed)
7. participation in a clinical study within 30 days before inclusion in the study or concomitantly
8. drug or alcohol abuse in the opinion of the investigator
9. Pregnant and lactating women

10. 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
    • Hormonal contraception
    • Intra Uterine Device
    • Double barrier method
    • Total abstinence throughout the study at the discretion of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Arm; Esflurbiprofen Hydrogel Patch containing 165 mg Esflurbiprofen	Drug: Esflurbiprofen Hydrogel Patch; Esflurbiprofen is a cyclooxygenase (COX) inhibitor
Placebo Comparator: Control Drug; Placebo patch that does not contain the active ingredient but is otherwise indistinguishable from the investigational drug Esflurbiprofen Hydrogel Patch	Drug: Esflurbiprofen Hydrogel Patch; Esflurbiprofen is a cyclooxygenase (COX) inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Pain-on-movement (POM) Compared to Baseline	Visual Analogue Scale (VAS) 0 = "no pain", 100 = "Extreme pain"	Change from baseline to Visit 5 (72 hours after initiating treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain-on-movement (POM) on VAS	Visual Analogue Scale (VAS) 0 = "no pain", 100 = "Extreme pain"	Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment
Area-under-the-curve for POM on VAS	Area-under-the-curve (AUC) over time during first 12, 24, 48, 72, 96 and 168 hours for Pain on movement (POM) measured using a VAS Visual Analogue Scale (VAS) 0 = "no pain", 100 = "Extreme pain"	Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment
Pain-at-rest on VAS	Visual Analogue Scale (VAS) 0 = "no pain", 100 = "Extreme pain"	Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment
Time to Meaningful and Optimal Reduction	The time taken to achieve a meaningful (30 %) and optimal (50 %) reduction of pain measured on the VAS for POM Visual Analogue Scale (VAS) 0 = "no pain", 100 = "Extreme pain"	Baseline and 12, 24, 48, 72, 96, 168 (192) hours after initiating treatment
Time to Complete Resolution of Pain	Time to complete resolution of pain, i. e. reaching a POM VAS value of 0 mm after start of study treatment Visual Analogue Scale (VAS) 0 = "no pain", 100 = "Extreme pain"	Baseline and 12, 24, 48, 72, 96, 168 (192) hours after initiating treatment
Responder Rate 1	defined as the percentage of patients achieving ≥50% reduction from baseline in the VAS score for POM at 72 hours Visual Analogue Scale (VAS) 0 = "no pain", 100 = "Extreme pain"	72 hours
Global Efficacy Assessments 1 by Patient	The global efficacy was assessed by the patients. The patients answered question below; -Considering all the ways this treatment has affected you since you started the clinical trial, how well are you doing? (5-point Likert scale: 0 = very good, 1 = good, 2 = fair, 3 = poor, and 4 = very poor). [Global efficacy assessment 1]	48 h, 72 h, and 168 h
Global Efficacy Assessments 2 by Patient	The global efficacy was assessed by the patients. The patients answered question below -How do you rate this medication as treatment for your soft injury/contusion? (5-point Likert scale: 0 = excellent, 1 = very good, 2 = good, 3 = fair, and 4 = poor). [Global efficacy assessment 2]	48 h, 72 h, and 168 h
Global Efficacy Assessments 1 by Investigator	The global efficacy was assessed by the investigator. -Considering all the ways this treatment has affected you since you started the clinical trial, how well are you doing? (5-point Likert scale: 0 = very good, 1 = good, 2 = fair, 3 = poor, and 4 = very poor). [Global efficacy assessment 1]	48 h, 72 h, and 168 h
Use of Rescue Medication	Rescue medication (paracetamol, 500 mg tablets, up to 3000 mg daily) was allowed during the study, except for the 6 hours prior to V5 (72 h).	0-168h
Resolution of Soft Tissue Injury/Contusion	Resolution of soft tissue injury/contusion was assessed by the Investigator at Visit 7 (168h).	168h
SPID of POM VAS Changes	The sum of pain intensity difference (SPID) of POM on VAS changes over 0-24 h, 0-48 h, 0-72 h, and 0-96 h were calculated. SPID was calculated as the area under the curve of the VAS difference from baseline value.	0-24 h, 0-48 h, 0-72 h, and 0-96 h
Responder Rate 2 at 168h	defined as the percentage of patients able to resume training/normal physical activity by 168 hours	168h

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adhesive Power of the Patch	Adhesive power of the patch measured by a 5 point numerical scale (0= ≥ 90 % adhered, 1= ≥ 75 % to < 90 % adhered, 2= ≥ 50 % to < 75 % adhered, 3= > 0 % to <50 % adhered, 4=completely detached) at every visit except V1.	12h for day 1, 24h for day 1-5 and 7 after application of each patch
Local Tolerability	Local tolerability was assessed by the Investigator according to the following numerical scale: 0: No evidence of irritation; Minimal erythema, barely perceptible; Definite erythema, readily visible, minimal edema or minimal papular response; Erythema and papules; Definite edema; Erythema, edema and papules; Vesicular eruption; Strong reaction spreading beyond test site	24, 48, 72, 96, 168h

Collaborators and Investigators

• Sponsor: Teikoku Seiyaku Co., Ltd.
• Collaborators: ClinSearch; Clinigen, Inc.; CRM Biometrics GmbH
• Investigators: Study Chair: Hiroshi Aoki, Teikoku Seiyaku Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Actual): November 9, 2021
• Study Completion (Actual): December 15, 2021

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Blunt Trauma
• Additional Relevant MeSH Terms: Wounds and Injuries; Wounds, Nonpenetrating; Soft Tissue Injuries; Sprains and Strains; Contusions
• Other Study ID Numbers: TK-254R-0201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No