Bruises, Contusions, Soft Tissue Injuries, Sprains, Strains
Conditions
Keywords
Blunt Trauma
Brief summary
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.
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
Interventions
Esflurbiprofen is a cyclooxygenase (COX) inhibitor
Sponsors
ClinSearch
CRM Biometrics GmbH
Clinigen, Inc.
Teikoku Seiyaku Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Packages of Investigative Medicinal product will be non-distinguishable to patients, study site staff and monitors. Randomization data are kept strictly confidential, accessible only to authorized persons, until the time of unblinding the identity of the treatments will be concealed by the use of study drugs that are all identical in packaging, labeling, schedule of administration, appearance and odor. Unblinding will only occur in the case of patient emergencies and at the conclusion of the study.
Intervention model description
Randomized, controlled, double-blind, multi-center
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Pain-on-movement (POM) Compared to Baseline | Change from baseline to Visit 5 (72 hours after initiating treatment) | Visual Analogue Scale (VAS) 0 = no pain, 100 = Extreme pain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain-on-movement (POM) on VAS | Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment | Visual Analogue Scale (VAS) 0 = no pain, 100 = Extreme pain |
| Area-under-the-curve for POM on VAS | Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment | 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 |
| Pain-at-rest on VAS | Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment | Visual Analogue Scale (VAS) 0 = no pain, 100 = Extreme pain |
| Time to Meaningful and Optimal Reduction | Baseline and 12, 24, 48, 72, 96, 168 (192) hours after initiating treatment | 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 |
| Time to Complete Resolution of Pain | Baseline and 12, 24, 48, 72, 96, 168 (192) hours after initiating treatment | 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 |
| Responder Rate 1 | 72 hours | 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 |
| Global Efficacy Assessments 1 by Patient | 48 h, 72 h, and 168 h | 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). \[Global efficacy assessment 1\] |
| SPID of POM VAS Changes | 0-24 h, 0-48 h, 0-72 h, and 0-96 h | 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. |
| Responder Rate 2 at 168h | 168h | defined as the percentage of patients able to resume training/normal physical activity by 168 hours |
| Global Efficacy Assessments 2 by Patient | 48 h, 72 h, and 168 h | 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). \[Global efficacy assessment 2\] |
| Global Efficacy Assessments 1 by Investigator | 48 h, 72 h, and 168 h | 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). \[Global efficacy assessment 1\] |
| Use of Rescue Medication | 0-168h | 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). |
| Resolution of Soft Tissue Injury/Contusion | 168h | Resolution of soft tissue injury/contusion was assessed by the Investigator at Visit 7 (168h). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adhesive Power of the Patch | 12h for day 1, 24h for day 1-5 and 7 after application of each 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. |
| Local Tolerability | 24, 48, 72, 96, 168h | Local tolerability was assessed by the Investigator according to the following numerical scale: 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 |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Arm Esflurbiprofen Hydrogel Patch containing 165 mg Esflurbiprofen | 98 |
| Control Drug Placebo patch that does not contain the active ingredient but is otherwise indistinguishable from the investigational drug Esflurbiprofen Hydrogel Patch | 102 |
| Total | 200 |
Baseline characteristics
| Characteristic | Control Drug | Total | Active Arm |
|---|---|---|---|
| Age, Continuous | 34.3 years STANDARD_DEVIATION 10.8 | 33.7 years STANDARD_DEVIATION 10.9 | 33.2 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 124 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 36 Participants | 73 Participants | 37 Participants |
| Region of Enrollment Germany | 102 participants | 200 participants | 98 participants |
| Sex: Female, Male Female | 47 Participants | 102 Participants | 55 Participants |
| Sex: Female, Male Male | 55 Participants | 98 Participants | 43 Participants |
| Type of injury Contusions | 72 Participants | 145 Participants | 73 Participants |
| Type of injury Sprains＆Strains | 30 Participants | 55 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 98 | 0 / 102 |
| other Total, other adverse events | 9 / 98 | 16 / 102 |
| serious Total, serious adverse events | 0 / 98 | 0 / 102 |
Outcome results
Primary
Change of Pain-on-movement (POM) Compared to Baseline
Visual Analogue Scale (VAS) 0 = no pain, 100 = Extreme pain
Time frame: Change from baseline to Visit 5 (72 hours after initiating treatment)
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Arm | Change of Pain-on-movement (POM) Compared to Baseline | -50.7 units on a scale | Standard Deviation 11.1 |
| Control Drug | Change of Pain-on-movement (POM) Compared to Baseline | -21.6 units on a scale | Standard Deviation 11.9 |
p-value: <0.000195% CI: [-32.2, -26]ANCOVA
Secondary
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
Time frame: Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Arm | Area-under-the-curve for POM on VAS | 0-12 h | 814.9 AUC of POM VAS pain (mm* h) | Standard Deviation 107 |
| Active Arm | Area-under-the-curve for POM on VAS | 0-24 h | 1424.5 AUC of POM VAS pain (mm* h) | Standard Deviation 210.3 |
| Active Arm | Area-under-the-curve for POM on VAS | 0-48 h | 2397.3 AUC of POM VAS pain (mm* h) | Standard Deviation 448.7 |
| Active Arm | Area-under-the-curve for POM on VAS | 0-72 h | 3026.1 AUC of POM VAS pain (mm* h) | Standard Deviation 655.8 |
| Active Arm | Area-under-the-curve for POM on VAS | 0-96 h | 3367.6 AUC of POM VAS pain (mm* h) | Standard Deviation 818.9 |
| Active Arm | Area-under-the-curve for POM on VAS | 0-168 h | 3771.4 AUC of POM VAS pain (mm* h) | Standard Deviation 1149.6 |
| Control Drug | Area-under-the-curve for POM on VAS | 0-96 h | 5300.7 AUC of POM VAS pain (mm* h) | Standard Deviation 1166.8 |
| Control Drug | Area-under-the-curve for POM on VAS | 0-12 h | 842.9 AUC of POM VAS pain (mm* h) | Standard Deviation 109.3 |
| Control Drug | Area-under-the-curve for POM on VAS | 0-72 h | 4242.4 AUC of POM VAS pain (mm* h) | Standard Deviation 730.3 |
| Control Drug | Area-under-the-curve for POM on VAS | 0-24 h | 1556.3 AUC of POM VAS pain (mm* h) | Standard Deviation 182.6 |
| Control Drug | Area-under-the-curve for POM on VAS | 0-168 h | 7285.7 AUC of POM VAS pain (mm* h) | Standard Deviation 1952.1 |
| Control Drug | Area-under-the-curve for POM on VAS | 0-48 h | 2970.3 AUC of POM VAS pain (mm* h) | Standard Deviation 415.3 |
Secondary
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). \[Global efficacy assessment 1\]
Time frame: 48 h, 72 h, and 168 h
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active Arm | Global Efficacy Assessments 1 by Investigator | 48h | Very poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 48h | Poor | 1 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 48h | Fair | 15 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 48h | Good | 35 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 48h | Very good | 47 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 72h | Poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 72h | Fair | 8 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 72h | Good | 35 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 72h | Very good | 55 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 168h | Very poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 168h | Poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 168h | Fair | 8 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 168h | Good | 31 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 168h | Very good | 59 Participants |
| Active Arm | Global Efficacy Assessments 1 by Investigator | 72h | Very poor | 0 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 168h | Poor | 19 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 48h | Very poor | 1 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 72h | Good | 14 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 48h | Poor | 20 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 168h | Good | 19 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 48h | Fair | 45 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 72h | Very good | 20 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 48h | Good | 17 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 168h | Fair | 42 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 168h | Very good | 21 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 48h | Very good | 19 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 168h | Very poor | 1 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 72h | Poor | 22 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 72h | Very poor | 0 Participants |
| Control Drug | Global Efficacy Assessments 1 by Investigator | 72h | Fair | 46 Participants |
Secondary
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). \[Global efficacy assessment 1\]
Time frame: 48 h, 72 h, and 168 h
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active Arm | Global Efficacy Assessments 1 by Patient | 48h | Fair | 15 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 48h | Good | 47 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 48h | Very good | 36 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 72h | Very poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 72h | Poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 72h | Fair | 6 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 72h | Very good | 51 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 168h | Very poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 168h | Poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 168h | Fair | 3 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 168h | Good | 36 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 168h | Very good | 59 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 48h | Very poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 48h | Poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 1 by Patient | 72h | Good | 41 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 168h | Good | 31 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 48h | Fair | 49 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 168h | Very poor | 1 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 48h | Good | 30 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 48h | Very poor | 2 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 48h | Very good | 8 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 168h | Poor | 11 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 72h | Very poor | 1 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 168h | Very good | 17 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 72h | Poor | 13 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 168h | Fair | 42 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 72h | Fair | 46 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 72h | Good | 31 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 48h | Poor | 13 Participants |
| Control Drug | Global Efficacy Assessments 1 by Patient | 72h | Very good | 11 Participants |
Secondary
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). \[Global efficacy assessment 2\]
Time frame: 48 h, 72 h, and 168 h
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active Arm | Global Efficacy Assessments 2 by Patient | 48h | Excellent | 11 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 72h | Very good | 50 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 48h | Fair | 12 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 72h | Excellent | 14 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 168h | Fair | 7 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 72h | Poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 168h | Poor | 0 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 48h | Very good | 47 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 72h | Fair | 7 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 168h | Good | 24 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 48h | Good | 28 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 168h | Very good | 46 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 72h | Good | 27 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 168h | Excellent | 21 Participants |
| Active Arm | Global Efficacy Assessments 2 by Patient | 48h | Poor | 0 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 168h | Excellent | 11 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 48h | Poor | 11 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 48h | Fair | 35 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 48h | Good | 36 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 48h | Very good | 15 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 48h | Excellent | 5 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 72h | Poor | 13 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 72h | Fair | 36 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 72h | Good | 32 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 72h | Very good | 12 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 72h | Excellent | 9 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 168h | Poor | 12 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 168h | Fair | 29 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 168h | Good | 37 Participants |
| Control Drug | Global Efficacy Assessments 2 by Patient | 168h | Very good | 13 Participants |
Secondary
Pain-at-rest on VAS
Visual Analogue Scale (VAS) 0 = no pain, 100 = Extreme pain
Time frame: Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Arm | Pain-at-rest on VAS | 24 h | 11.2 units on a scale | Standard Deviation 5.4 |
| Active Arm | Pain-at-rest on VAS | 72 h | 4.1 units on a scale | Standard Deviation 3.4 |
| Active Arm | Pain-at-rest on VAS | 12 h | 14.7 units on a scale | Standard Deviation 6.1 |
| Active Arm | Pain-at-rest on VAS | 96 h | 2.0 units on a scale | Standard Deviation 2.7 |
| Active Arm | Pain-at-rest on VAS | 48 h | 7.5 units on a scale | Standard Deviation 4.6 |
| Active Arm | Pain-at-rest on VAS | 168 h | 0.5 units on a scale | Standard Deviation 1.5 |
| Active Arm | Pain-at-rest on VAS | Baseline | 17.9 units on a scale | Standard Deviation 5.9 |
| Control Drug | Pain-at-rest on VAS | 168 h | 3.7 units on a scale | Standard Deviation 4.4 |
| Control Drug | Pain-at-rest on VAS | Baseline | 17.0 units on a scale | Standard Deviation 7.7 |
| Control Drug | Pain-at-rest on VAS | 12 h | 15.2 units on a scale | Standard Deviation 6.4 |
| Control Drug | Pain-at-rest on VAS | 24 h | 13.5 units on a scale | Standard Deviation 6.2 |
| Control Drug | Pain-at-rest on VAS | 48 h | 11.5 units on a scale | Standard Deviation 6.2 |
| Control Drug | Pain-at-rest on VAS | 72 h | 9.2 units on a scale | Standard Deviation 5.5 |
| Control Drug | Pain-at-rest on VAS | 96 h | 6.5 units on a scale | Standard Deviation 5.4 |
Secondary
Pain-on-movement (POM) on VAS
Visual Analogue Scale (VAS) 0 = no pain, 100 = Extreme pain
Time frame: Baseline and 12, 24, 48, 72, 96, 168 hours after initiating treatment
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Arm | Pain-on-movement (POM) on VAS | 24 hour | 48.8 units on a scale | Standard Deviation 12.2 |
| Active Arm | Pain-on-movement (POM) on VAS | 72 hour | 19.2 units on a scale | Standard Deviation 9.7 |
| Active Arm | Pain-on-movement (POM) on VAS | 12 hour | 61.1 units on a scale | Standard Deviation 10.3 |
| Active Arm | Pain-on-movement (POM) on VAS | 96 hour | 9.2 units on a scale | Standard Deviation 8.3 |
| Active Arm | Pain-on-movement (POM) on VAS | 48 hour | 33.3 units on a scale | Standard Deviation 11.9 |
| Active Arm | Pain-on-movement (POM) on VAS | 168 hour | 2.1 units on a scale | Standard Deviation 4.4 |
| Active Arm | Pain-on-movement (POM) on VAS | Baseline | 69.9 units on a scale | Standard Deviation 7.6 |
| Control Drug | Pain-on-movement (POM) on VAS | 168 hour | 19.4 units on a scale | Standard Deviation 17.4 |
| Control Drug | Pain-on-movement (POM) on VAS | Baseline | 70.1 units on a scale | Standard Deviation 8.3 |
| Control Drug | Pain-on-movement (POM) on VAS | 12 hour | 66.4 units on a scale | Standard Deviation 8.4 |
| Control Drug | Pain-on-movement (POM) on VAS | 24 hour | 62.8 units on a scale | Standard Deviation 10.4 |
| Control Drug | Pain-on-movement (POM) on VAS | 48 hour | 56.6 units on a scale | Standard Deviation 12 |
| Control Drug | Pain-on-movement (POM) on VAS | 72 hour | 48.5 units on a scale | Standard Deviation 14.9 |
| Control Drug | Pain-on-movement (POM) on VAS | 96 hour | 37.3 units on a scale | Standard Deviation 16.7 |
Secondary
Resolution of Soft Tissue Injury/Contusion
Resolution of soft tissue injury/contusion was assessed by the Investigator at Visit 7 (168h).
Time frame: 168h
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Arm | Resolution of Soft Tissue Injury/Contusion | 92 Participants |
| Control Drug | Resolution of Soft Tissue Injury/Contusion | 49 Participants |
Secondary
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
Time frame: 72 hours
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Arm | Responder Rate 1 | 93 Participants |
| Control Drug | Responder Rate 1 | 15 Participants |
Secondary
Responder Rate 2 at 168h
defined as the percentage of patients able to resume training/normal physical activity by 168 hours
Time frame: 168h
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Arm | Responder Rate 2 at 168h | 92 Participants |
| Control Drug | Responder Rate 2 at 168h | 49 Participants |
Secondary
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.
Time frame: 0-24 h, 0-48 h, 0-72 h, and 0-96 h
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Active Arm | SPID of POM VAS Changes | 0-24 h | 342.5 SPID of POM on VAS (mm x h) |
| Active Arm | SPID of POM VAS Changes | 0-48 h | 1211.1 SPID of POM on VAS (mm x h) |
| Active Arm | SPID of POM VAS Changes | 0-72 h | 2425.1 SPID of POM on VAS (mm x h) |
| Active Arm | SPID of POM VAS Changes | 0-96 h | 3881.4 SPID of POM on VAS (mm x h) |
| Control Drug | SPID of POM VAS Changes | 0-96 h | 1753.7 SPID of POM on VAS (mm x h) |
| Control Drug | SPID of POM VAS Changes | 0-24 h | 126.6 SPID of POM on VAS (mm x h) |
| Control Drug | SPID of POM VAS Changes | 0-72 h | 965.5 SPID of POM on VAS (mm x h) |
| Control Drug | SPID of POM VAS Changes | 0-48 h | 445.9 SPID of POM on VAS (mm x h) |
Secondary
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
Time frame: Baseline and 12, 24, 48, 72, 96, 168 (192) hours after initiating treatment
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Arm | Time to Complete Resolution of Pain | 48-72h | 2 Participants |
| Active Arm | Time to Complete Resolution of Pain | 72-96h | 10 Participants |
| Active Arm | Time to Complete Resolution of Pain | 96-192h | 45 Participants |
| Active Arm | Time to Complete Resolution of Pain | Not achieved | 41 Participants |
| Control Drug | Time to Complete Resolution of Pain | Not achieved | 92 Participants |
| Control Drug | Time to Complete Resolution of Pain | 48-72h | 0 Participants |
| Control Drug | Time to Complete Resolution of Pain | 96-192h | 10 Participants |
| Control Drug | Time to Complete Resolution of Pain | 72-96h | 0 Participants |
Secondary
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
Time frame: Baseline and 12, 24, 48, 72, 96, 168 (192) hours after initiating treatment
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active Arm | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | < 12 | 8 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 12-24 | 41 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 24-48 | 42 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 48-72 | 7 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 72-96 | 0 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 96-192 | 0 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | Not achieved | 0 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | < 12 | 2 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 12-24 | 4 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 24-48 | 51 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 48-72 | 36 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 72-96 | 5 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 96-192 | 0 Participants |
| Active Arm | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | Not achieved | 0 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 48-72 | 13 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | < 12 | 1 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | < 12 | 0 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 12-24 | 3 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 96-192 | 42 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 24-48 | 10 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 12-24 | 1 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 48-72 | 33 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 72-96 | 26 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 72-96 | 35 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | 24-48 | 1 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | 96-192 | 15 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to optimal reduction of pain (h) (50 % or more) | Not achieved | 19 Participants |
| Control Drug | Time to Meaningful and Optimal Reduction | Time to meaningful reduction of pain (h) (30% or more) | Not achieved | 5 Participants |
Secondary
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).
Time frame: 0-168h
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Arm | Use of Rescue Medication | 0 Participants |
| Control Drug | Use of Rescue Medication | 0 Participants |
Other Pre-specified
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.
Time frame: 12h for day 1, 24h for day 1-5 and 7 after application of each patch
Population: The Full Analysis Set (all randomized patients who received at least one dose of study drug).
| Arm | Measure | Group | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|---|
| Active Arm | Adhesive Power of the Patch | 12h | Completely detached | 1 Number of patches |
| Active Arm | Adhesive Power of the Patch | 12h | ≥ 0 % to < 50 % adhered | 0 Number of patches |
| Active Arm | Adhesive Power of the Patch | 12h | ≥ 50 % to < 75 % adhered | 23 Number of patches |
| Active Arm | Adhesive Power of the Patch | 12h | ≥ 75 % to < 90 % adhered | 46 Number of patches |
| Active Arm | Adhesive Power of the Patch | 12h | ≥ 90 % adhered | 28 Number of patches |
| Active Arm | Adhesive Power of the Patch | 24h | Completely detached | 0 Number of patches |
| Active Arm | Adhesive Power of the Patch | 24h | ≥ 0 % to < 50 % adhered | 10 Number of patches |
| Active Arm | Adhesive Power of the Patch | 24h | ≥ 50 % to < 75 % adhered | 101 Number of patches |
| Active Arm | Adhesive Power of the Patch | 24h | ≥ 75 % to < 90 % adhered | 202 Number of patches |
| Active Arm | Adhesive Power of the Patch | 24h | ≥ 90 % adhered | 177 Number of patches |
| Control Drug | Adhesive Power of the Patch | 24h | ≥ 50 % to < 75 % adhered | 145 Number of patches |
| Control Drug | Adhesive Power of the Patch | 12h | Completely detached | 0 Number of patches |
| Control Drug | Adhesive Power of the Patch | 24h | Completely detached | 1 Number of patches |
| Control Drug | Adhesive Power of the Patch | 12h | ≥ 0 % to < 50 % adhered | 4 Number of patches |
| Control Drug | Adhesive Power of the Patch | 24h | ≥ 90 % adhered | 148 Number of patches |
| Control Drug | Adhesive Power of the Patch | 12h | ≥ 50 % to < 75 % adhered | 27 Number of patches |
| Control Drug | Adhesive Power of the Patch | 24h | ≥ 0 % to < 50 % adhered | 10 Number of patches |
| Control Drug | Adhesive Power of the Patch | 12h | ≥ 75 % to < 90 % adhered | 51 Number of patches |
| Control Drug | Adhesive Power of the Patch | 24h | ≥ 75 % to < 90 % adhered | 206 Number of patches |
| Control Drug | Adhesive Power of the Patch | 12h | ≥ 90 % adhered | 20 Number of patches |
Other Pre-specified
Local Tolerability
Local tolerability was assessed by the Investigator according to the following numerical scale: 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
Time frame: 24, 48, 72, 96, 168h
Population: Safety Set (SAF) The safety set included all randomized patients who received at least one dose of the study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active Arm | Local Tolerability | 48h | No evidence of irritation (0) | 95 Participants |
| Active Arm | Local Tolerability | 96h | Minimal erythema (1) | 1 Participants |
| Active Arm | Local Tolerability | 48h | Minimal erythema (1) | 3 Participants |
| Active Arm | Local Tolerability | 96h | No evidence of irritation (0) | 97 Participants |
| Active Arm | Local Tolerability | 72h | Minimal erythema (1) | 4 Participants |
| Active Arm | Local Tolerability | 168h | Minimal erythema (1) | 4 Participants |
| Active Arm | Local Tolerability | 24h | No evidence of irritation (0) | 95 Participants |
| Active Arm | Local Tolerability | 168h | No evidence of irritation (0) | 94 Participants |
| Active Arm | Local Tolerability | 72h | No evidence of irritation (0) | 94 Participants |
| Active Arm | Local Tolerability | 24h | Minimal erythema (1) | 3 Participants |
| Control Drug | Local Tolerability | 24h | Minimal erythema (1) | 4 Participants |
| Control Drug | Local Tolerability | 24h | No evidence of irritation (0) | 98 Participants |
| Control Drug | Local Tolerability | 48h | Minimal erythema (1) | 9 Participants |
| Control Drug | Local Tolerability | 48h | No evidence of irritation (0) | 93 Participants |
| Control Drug | Local Tolerability | 72h | Minimal erythema (1) | 6 Participants |
| Control Drug | Local Tolerability | 72h | No evidence of irritation (0) | 96 Participants |
| Control Drug | Local Tolerability | 96h | Minimal erythema (1) | 4 Participants |
| Control Drug | Local Tolerability | 96h | No evidence of irritation (0) | 98 Participants |
| Control Drug | Local Tolerability | 168h | Minimal erythema (1) | 4 Participants |
| Control Drug | Local Tolerability | 168h | No evidence of irritation (0) | 98 Participants |