Clinical trial NCT04976088: Clinical Trial With Diclofenac Sodium Medicated Plaster in Patients With Impact Injuries of the Limbs
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Trauma Injury
Inflammation
Keywords: traumatic
Lead sponsor: Fidia Farmaceutici s.p.a.
Sponsor class: INDUSTRY
First posted: 2021-07-26
Enrollment: 214
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 72 hours
Secondary outcomes:
measure: Area under the curve (AUC) for pain at rest at Day 4 and Day 8 (SPID0-4d and SPID0-8d)
timeFrame: Day 4 and Day 8
measure: 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.
timeFrame: Day 1, Day 2, Day 3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: 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.
timeFrame: From Day 1 until the date of resolution of pain at rest (maximum Day 8)
measure: 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
timeFrame: Day 4 and Day 8
measure: 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
timeFrame: Day 4
measure: Proportion of patients that used rescue medication (paracetamol) from Baseline to Day 8 usign a patient diary
timeFrame: From Baseline to Day 8
measure: Amount of tablets of rescue medication consumed from Baseline to Day 8, using a patient diary
timeFrame: From Baseline to Day 8
measure: 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
timeFrame: Day 1, Day 2, Day 3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: Safety as change from baseline to Day 8 evaluated by physical examination using observation, palpitation, percussion, and auscultation
timeFrame: Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: Safety as change from baseline to Day 8 evaluated by systolic blood pressure measured in mmHg
timeFrame: Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: Safety as change from baseline to Day 8 evaluated by diastolic blood pressure measured in mmHg
timeFrame: Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: Safety as change from baseline to Day 8 evaluated by heart rate measured in bpm
timeFrame: Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: Safety as change from baseline to Day 8 evaluated by tracking the number of patient withdrawals
timeFrame: Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: Safety as change from baseline to Day 8 evaluated by tracking the number of adverse events
timeFrame: Day 1, Day 2, Day3, Day 4, Day 5,Day 6, Day 7, Day 8
measure: 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
timeFrame: Day 1, Day 4 and Day 8
measure: 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
timeFrame: Day 1, Day 4 and Day 8
measure: 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
timeFrame: Day 1, Day 4 and Day 8
measure: 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
timeFrame: Day 1, Day 4 and Day 8
measure: 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.
timeFrame: Day 4 and Day 8
Other outcomes:
Locations:
city: Gilching
country: Germany
facility: Praxis Dr. med. Helmut Pabst
city: Rheinbach
country: Germany
facility: Praxis Dr. Jürgen Ulrich Schaale-Maas
city: Budapest
country: Hungary
facility: Synexus Budapest DRC
city: Budapest
country: Hungary
facility: Magyar Honvédség, Egészségügyi Központ Baleseti Sebészeti Osztály
city: Budapest
country: Hungary
facility: Uzsoki utcai Kórház Ortopéd-traumatológiai Osztály
city: Debrecen
country: Hungary
facility: Synexus Debrecen AS
city: Eger
country: Hungary
facility: Platán Egészségcentrum
city: Gyula
country: Hungary
facility: Synexus Magyarország kft. Gyula DRS
city: Kalocsa
country: Hungary
facility: Shawfar-med Kft
city: Kecskemét
country: Hungary
facility: Jutrix Kft.
city: Kiskunfélegyháza
country: Hungary
facility: Bács-Kiskun Megyei Kórház Kiskunfélegyházi Városi Kórház és Rendelőintézet
city: Makó
country: Hungary
facility: G&V Pharma-Med Bt.
city: Nagyatád
country: Hungary
facility: Nagyatádi Kórház Reumatológiai Osztály
city: Zalaegerszeg
country: Hungary
facility: Synexus Magyarország EÜ szolg Kft.
city: Sant'olcese chiesa
country: Italy
facility: Ambulatorio MMG dott. Paolo Picco
state: Genova
city: Genova
country: Italy
facility: Ambulatorio MMG dott. Andrea Pedemonte
Study officials:
affiliation: Fidia Farmaceutici s.p.a.
name: Nicola Giordan
role: STUDY_DIRECTOR
References: