Clinical Trial With Diclofenac Sodium Medicated Plaster in Patients With Impact Injuries of the Limbs

Randomized, Double Blind, Parallel-groups, Non-inferiority Versus Flector® and Superiority Versus Placebo, Phase III Clinical Trial With Diclofenac Sodium 140 mg Medicated Plaster in Patients With Impact Injuries of the Limbs

Phase III, multinational, multicentre, randomized, prospective, double blind, parallel groups, placebo-controlled study to evaluate the analgesic effects of Test Diclofenac Sodium 140mg medicated plaster, Reference DIEP 180 mg medicated plaster, Flector® and Placebo plaster in patients with painful and phlogistic disease due to acute traumatic events of the limbs.

Study Overview

• Status: Completed
• Conditions: Inflammation; Trauma Injury
• Intervention / Treatment: Drug: Diclofenac Sodium 140 mg medicated plaster; Drug: Diclofenac epolamine (DIEP) 180mg medicated plaster, Flector; Drug: Placebo

Detailed Description

This will be a Phase III, multinational, multicentre, randomized, prospective, double blind, parallel groups, placebo-controlled study to evaluate the analgesic effects of Test Diclofenac Sodium 140mg medicated plaster (once a day), Reference DIEP 180 mg medicated plaster, Flector® (once a day) and Placebo plaster once a day (i.e. the placebo arm) in patients with painful and phlogistic (inflammatory response) disease due to acute traumatic events (injury/contusion) of the limbs.

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Gilching, Germany, 82205
    • Praxis Dr. med. Helmut Pabst
  • Rheinbach, Germany, 53359
    • Praxis Dr. Jürgen Ulrich Schaale-Maas
• Hungary
  • Budapest, Hungary, 1036
    • Synexus Budapest DRC
  • Budapest, Hungary, 1134
    • Magyar Honvédség, Egészségügyi Központ Baleseti Sebészeti Osztály
  • Budapest, Hungary, 1146
    • Uzsoki utcai Kórház Ortopéd-traumatológiai Osztály
  • Debrecen, Hungary, 4025
    • Synexus Debrecen AS
  • Eger, Hungary, 3300
    • Platán Egészségcentrum
  • Gyula, Hungary, 5700
    • Synexus Magyarorszag Kft. Gyula DRS
  • Kalocsa, Hungary, 6300
    • Shawfar-med Kft
  • Kecskemét, Hungary, 6000
    • Jutrix Kft.
  • Kiskunfélegyháza, Hungary, 6101
    • Bács-Kiskun Megyei Kórház Kiskunfélegyházi Városi Kórház és Rendelőintézet
  • Makó, Hungary, 6901
    • G&V Pharma-Med Bt.
  • Nagyatád, Hungary, 7500
    • Nagyatádi Kórház Reumatológiai Osztály
  • Zalaegerszeg, Hungary, 8900
    • Synexus Magyarország EÜ szolg Kft.
• Italy
  • Genova, Italy, 16162
    • Ambulatorio MMG dott. Andrea Pedemonte
  • Genova
    • Sant'olcese chiesa, Genova, Italy, 16010
      • Ambulatorio MMG dott. Paolo Picco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, age range 18-65 years (included);
2. Patient with painful and phlogistic (inflammatory response) disease due to acute traumatic events (injury/contusion) of the limbs;
3. Patient with pain at rest in only one limb surface area affected by injury/contusion;
4. Written informed consent to participate in the study obtained according to GCP;
5. Patients able to comprehend the full nature and the purpose of the study, including possible risks and side effects, and able to cooperate with the Investigator and to comply with the requirements of the entire study (including ability to attend all the planned study visits according to the time limits), based on Investigator's judgement;
6. Good general health as determined by the Investigator based on medical history and physical examination;
7. Female of child-bearing potential (i.e. not in menopausal status from at least one year or permanently sterilized) must have a negative urine pregnancy test prior the first IMP administration;
8. Presence of pain at rest in the injured area, defined by patient with a VAS ≥40 mm and ≤80 mm at Visit 1 on a 100 mm VAS

Exclusion Criteria:

1. Patient with a chronic painful or phlogistic disease (from more than three months);
2. Patient with painful or phlogistic disease arising from fractures or severe trauma events;
3. Pregnancy or lactation period throughout the whole study duration;
4. If female and of child-bearing potential, patient not using a highly effective method of birth control. Highly effective birth control methods include: combined hormonal contraception (containing estrogen and progestogen) associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised partner; sexual abstinence*;
5. Presence of concurrent skin disorders or open wounds in the area to be treated;
6. History of alcohol or drug abuse;
7. History of allergy or hypersensitivity or intolerance to diclofenac and/or to active or inactive excipients of formulation;
8. Known hypersensitivity to non-steroidal anti-inflammatory drugs and to paracetamol;
9. Use of non-steroid anti-inflammatory drugs and analgesics in the week before Visit 1 (with the exception of paracetamol, which should not be taken in the previous 8 hours), oral corticosteroids within 2 weeks or intravenous corticosteroids within 4 weeks before Visit 1. Chronic intake of small doses of acetylsalicylic acid (≤ 162 mg/day) taken for at least 30 days prior to the first dose of study medication for non-analgesic reasons may be continued (with no change on dosage) for the duration of the study;
10. Any other treatment or medication for the same or other indications that, according to its pharmacological properties and in the opinion of the Investigator, can alter the perception of pain (e.g. heparinoids or other anticoagulant agents, opioids, psychotropic agents, anti H1 agents or analgesics like glucocorticosteroids, etc.) in the week before Visit 1;
11. Any other concomitant treatment (e.g. cosmetics, ointments at the treated area) or medication that cannot be interrupted and interferes with the conduct of the trial;
12. History of active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration or bleeding within 30 days before Visit 1;
13. History of uncontrolled chronic or acute concomitant disease (e.g. cardiac dysfunction, liver dysfunction, hemorrhagic diathesis, …) which, in the Investigator's opinion, would contraindicate study participation or confound interpretation of the results;
14. Known malignant diseases in the last 5 years;
15. Pre-treatment of the traumatic event (injury/contusion) target of this study. Previous cooling (with ice, cooling spray) is authorized prior to Visit 1 (but not in the three hours preceding Visit 1);
16. Anticipated poor compliance by the patient;
17. Previous participation in this clinical trial;
18. Any relevant surgical treatment during the previous 2 months or planned during the trial;
19. Patient with a history of serious psychiatric disorders;
20. Participation in any other clinical study within 30 days prior to Visit 1. *Note: According to 4.1 paragraph "Birth control methods which may be considered as highly effective" of the CTFG/Recommendations related to contraception and pregnancy testing in clinical trials

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A Test; Test product: treated once a day (morning) with the medicated plaster containing 140 mg Diclofenac Sodium for seven days Diclofenac Sodium 140 mg medicated plaster	Drug: Diclofenac Sodium 140 mg medicated plaster; Test product: Diclofenac Sodium 140 mg medicated plaster, topical application once a day; Other Names: EQI7
Active Comparator: Group B Reference; Reference product: treated once a day (morning) with the medicated plaster containing DIEP 180 mg, Flector® for seven days Diclofenac epolamine (DIEP) 180 mg medicated plaster, Flector®	Drug: Diclofenac epolamine (DIEP) 180mg medicated plaster, Flector; Reference product: Active-comparator, Diclofenac epolamine (DIEP) 180 mg medicated plaster, Flector®, topical application once a day; Other Names: Flector
Placebo Comparator: Group C Placebo; Placebo: treated once a day (morning) with the placebo plaster for seven days	Drug: Placebo; Placebo: Placebo plaster, topical application once a day.; Other Names: Placebo plaster

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in VAS score (Visual Analogue Scale from 0 to 100 mm, where the left extreme means "No pain = 0" while the right extreme means "Worst Pain Imaginable = 100") for pain at rest at 72 ± 2 hours (Day 4) after treatment start.	Non-inferior efficacy of Test (once a day) over Reference (once a day) in reduction of pain after 3 days post-Baseline (72± 2 hours, Day 4), and superior efficacy of Test and Reference to Placebo (once a day) in improving pain at rest at 72 ± 2 hours (Day 4) after Baseline in patients with painful and phlogistic disease due to acute traumatic events of the limbs. A 100-mm Visual Analogue Scale (VAS) will be used for the assessment of pain at rest, from 0 to 100, where "No pain = 0" while "Worst Pain Imaginable = 100".	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) for pain at rest at Day 4 and Day 8 (SPID0-4d and SPID0-8d)	To compare Test to Reference and Placebo with regard to pain relief (pain at rest and pain on movement) at Day 4 and Day8, assessed through the AUC (Area Under the Curve) of VAS measurements (Visual Analogue Scale from 0 to 100 mm, where the left extreme means "No pain = 0" while the right extreme means "Worst Pain Imaginable = 100") at Day 4 and Day 8.	Day 4 and Day 8
Change from baseline of VAS (Visual Analogue Scale 0-100 mm, where "No pain = 0" and "Worst Pain Imaginable = 100") for pain at rest at the other study time-points (including patients' home measurements), from Day 1 to Day 8.	To compare efficacy of the Test product to Reference and Placebo with regard to pain relief (pain at rest and pain on movement) from Day 1 to Day 8.	Day 1, Day 2, Day 3, Day 4, Day 5,Day 6, Day 7, Day 8
Time to resolution of pain at rest, measured through VAS Scale (Visual Analogue Scale 0-100 mm, where "No pain = 0" and "Worst Pain Imaginable = 100") during from Baseline to Day 8.	To compare efficacy of Test in comparison to Reference and Placebo with regard to time to resolution of pain (pain at rest and pain on movement), measured with VAS score (Visual Analogue Scale 0-100 mm, where "No pain = 0" and "Worst Pain Imaginable = 100").	From Day 1 until the date of resolution of pain at rest (maximum Day 8)
Change from baseline in VAS score (Visual Analogue Scale 0-100 mm, where "No pain = 0" and "Worst Pain Imaginable = 100") for pain on movement at 72 ± 2 hours (Day 4) and at 168 ± 2 hours (Day 8) after treatment start	To compare efficacy of Test to Reference and Placebo with regard to pain relief (pain on movement), measured with VAS score (Visual Analogue Scale 0-100 mm, where "No pain = 0" and "Worst Pain Imaginable = 100") at Day 4 and Day 8.	Day 4 and Day 8
Proportion of responder patients (defined as a decrease ≥ 50% of baseline VAS (Visual Analogue Scale 0-100 mm, where "No pain = 0" and "Worst Pain Imaginable = 100") for pain at rest and on movement) at 72 ± 2 hours (Day 4) after treatment start	To compare efficacy of Test to Reference and Placebo with regard to proportion of responders to pain relief (pain at rest and pain on movement) at Day 4, considering a decrease as ≥ 50% of baseline VAS (Visual Analogue Scale 0-100 mm, where "No pain = 0" and "Worst Pain Imaginable = 100")	Day 4
Proportion of patients that used rescue medication (paracetamol) from Baseline to Day 8 usign a patient diary	To compare the proportion of patients that used rescue medication from Baseline to Day 8 among the three treatment arms (Test, Refrence and Placebo) using a patient diary	From Baseline to Day 8
Amount of tablets of rescue medication consumed from Baseline to Day 8, using a patient diary	To compare the amount of consumption of tablets of paracetamol among the three treatment arms (Test, Refrence and Placebo) using a patient diary	From Baseline to Day 8
IMP adhesion, performed daily by patients and at Day 4 and Day 8 by the open staff member; following 5-point ordinal scale: 0:≥90% adhered; 1:≥75% to <90% adhered; 2:≥50% to <75% adhered; 3:<50% adhered but not detached; 4:Plaster detached	To compare the adhesion of Test to Reference and Placebo in the site of application from Baseline to Day 8, 5-point ordinal scale: 0:≥90% adhered; 1:≥75% to <90% adhered; 2:≥50% to <75% adhered; 3:<50% adhered but not detached; 4:Plaster detached	Day 1, Day 2, Day 3, Day 4, Day 5,Day 6, Day 7, Day 8
Safety as change from baseline to Day 8 evaluated by physical examination using observation, palpitation, percussion, and auscultation	To compare Test with Reference and Placebo in patient safety as change from baseline to Day 8 using observation, palpitation, percussion, and auscultation	Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
Safety as change from baseline to Day 8 evaluated by systolic blood pressure measured in mmHg	To compare Test with Reference and Placebo in systolic blood pressure, measured in mmHg, as change from baseline to Day 8	Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
Safety as change from baseline to Day 8 evaluated by diastolic blood pressure measured in mmHg	To compare Test with Reference and Placebo in diastolic blood pressure, measured in mmHg, as change from baseline to Day 8	Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
Safety as change from baseline to Day 8 evaluated by heart rate measured in bpm	To compare Test with Reference and Placebo in heart rate, measured in bpm, as change from baseline to Day 8	Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
Safety as change from baseline to Day 8 evaluated by tracking the number of patient withdrawals	To compare Test with Reference and Placebo in patient safety as change from baseline to Day 8, tracking the number of withdrawals	Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
Safety as change from baseline to Day 8 evaluated by tracking the number of adverse events	To compare Test with Reference and Placebo in patient safety as change from baseline to Day 8, tracking the number of adverse events	Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
Local tolerability (erythema) at the IMP application site by Investigator at Day 1, Day 4 and Day 8 based on a 8-point categorical scale, where 0=no evidence of irritation and 7=strong reaction spreading beyond test site	To compare Test with Reference and Placebo in relation to the level of irritation on the application site	Day 1, Day 4 and Day 8
Local tolerability (itching) at the IMP application site by Investigator at Day 1, Day 4 and Day 8 based on a 4-point categorical scale, where 0=absent and 3=severe	To compare Test with Reference and Placebo in relation to the level of itching on the application site	Day 1, Day 4 and Day 8
Local tolerability (burning) at the IMP application site by Investigator at Day 1, Day 4 and Day 8 based on a 4-point categorical scale, where 0=absent and 3=severe	To compare Test with Reference and Placebo in relation to the level of burning on the application site	Day 1, Day 4 and Day 8
Local tolerability (local pain) at the IMP application site by Investigator at Day 1, Day 4 and Day 8 based on a 4-point categorical scale, where 0=absent and 3=severe	To compare Test with Reference and Placebo in relation to the level of local pain on the application site	Day 1, Day 4 and Day 8
Global assessment of local tolerability at IMP administration site by Investigator and patient according to the following score: 3=excellent; 2=good; 1=fair; 0=poor, assessed at Day 4 and Day 8.	To compare Test with Reference and Placebo in relation to the global assessment of local tolerability on the application site	Day 4 and Day 8

Collaborators and Investigators

• Sponsor: Fidia Farmaceutici s.p.a.
• Investigators: Study Director: Nicola Giordan, Fidia Farmaceutici s.p.a.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2018
• Primary Completion (Actual): October 27, 2018
• Study Completion (Actual): October 27, 2018

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 26, 2021

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 29, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: traumatic
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Wounds and Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac; Diclofenac hydroxyethylpyrrolidine
• Other Study ID Numbers: EQI7_16_02

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