E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute pain in mild/moderate ankle sprains |
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E.1.1.1 | Medical condition in easily understood language |
Acute pain in mild/moderate ankle sprains |
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E.1.1.2 | Therapeutic area | Diseases [C] - Injuries, poisonings, and occupational diseases [C21] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10024453 |
E.1.2 | Term | Ligament sprain |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10022117 |
E.1.2 | Term | Injury, poisoning and procedural complications |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028288 |
E.1.2 | Term | Muscle, tendon and ligament injuries |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess whether DHEP 2.6% medicated plaster applied once-a-day for 7 days is superior in relieving pain due to recent mild/moderate ankle sprain, as compared to a placebo (vehicle) plaster. To assess if DHEP 2.6% medicated plaster applied once-a-day for 7 days is non-inferior in relieving pain due to recent mild/moderate ankle sprain, as compared to the reference marketed product Flector®, applied twice-a-day (two applications of 12 h each) during the 7-day treatment period. |
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E.2.2 | Secondary objectives of the trial |
Evaluation the tested products in terms of: effect on ankle oedema effect on ankle joint function effect on rescue medication intake Investigator's judgment of global efficacy adhesion (including use of reinforcement with an elastic net sleeve, as needed) subject's compliance to treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Male or female outpatients, aged ≥ 18 and ≤ 65 years; 2. Acute Grade I or II ankle sprain involving the lateral ligaments (i.e., inversion mechanism); 3. Ankle sprain occurred ≤ 48 hours before inclusion in the study; 4. Ankle sprain with pain on movement (while performing normal daily activities) with a score of ≥ 5 on the Numeric Rating Scale (NRS); 5. Females of childbearing potential (i.e., not permanently sterilised - post hysterectomy or tubal ligation status – or not postmenopausal) must have a negative urine pregnancy test result at screening/inclusion visit and must use an appropriate method of contraception for at least 30 days before inclusion in the study and for 7 days after the last dose, according to the definition in ICH M3 (R2) Guidelines; 6. Subject having provided their written informed consent to study participation. |
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E.4 | Principal exclusion criteria |
1. Positive or missing pregnancy test at screening/inclusion visit, or breast-feeding women; 2. Sprain occurred > 48 h prior to study enrolment; 3. Severe (Grade III) ankle sprain or ankle sprain requiring an orthopaedic, surgical or physiotherapeutic treatment; 4. Baseline (pre-treatment) self-evaluation of pain on movement by NRS of ≤ 5; 5. Non-intact or damaged skin within the area to be treated, e.g., eczema, psoriasis, exudative dermatitis, infected lesion, burn or wound; 6. Three or more prior injuries to the affected ankle in the past; 7. Relapsing sprains already treated during the 6 months preceding the study inclusion; 8. Any other significant injury (such as fracture or torn ligament), or surgery (except for skin and nails) of the affected ankle or foot during the past 6 months; 9. Prior use of any topical medication to the affected area within 48 hours to inclusion in the study; 10. Prior use of analgesic, NSAIDs, or COX-inhibitors, by any route, within 48 hours or 5 half-lives before inclusion in the study, whichever is longer (oral paracetamol permitted until 3 hours before inclusion/baseline pain assessment). Use of stable daily doses of aspirin taken for non-analgesic reasons for at least 30 days prior to inclusion may be continued for the duration of the study; 11. Prior use of narcotic analgesics within 7 days before study entry, prior use of systemic corticosteroids by any route of administration within 60 days preceding inclusion in the study; 12. Ankle sprain treated prior to inclusion in the study with physiotherapy, ultrasound, acupuncture or physical therapy (RICE permitted until 3 hours before inclusion/baseline pain assessment); 13. Use within 30 days prior to inclusion of immunomodulators or immunosuppressive therapies or interferon; 14. Known allergy or hypersensitivity to diclofenac, aspirin or other NSAIDs, including paracetamol, or any excipient in the tested products; 15. Medical history of: - asthma, urticaria, angioedema, or bronchospasm; - ulcer disease, gastrointestinal bleeding, inflammatory bowel disease; - coagulation defects, hemorrhagic diathesis; - severe hepatic or renal impairment; - severe cardiac/cardiovascular conditions, including NYHA Class III and IV congestive heart failure (CHF), and unstable, uncontrolled hypertension; - any chronic pain disorder; - severe systemic disease (e.g., cancer, severe acute infection); 16. Major psychiatric disorders that, according to the Investigator, could compromise the subject’s participation in the study; 17. History of alcohol or drug abuse (within previous 12 months); 18. Subjects refusing to give a written informed consent; 19. Concomitant participation in other clinical trials or participation in the evaluation of any investigational product during 3 months before this study or previous participation in the same study; 20. Participation in the study is also not permitted to employees of the Investigator or study site with direct involvement in the trial or in other trials under the direction of that Investigator, as well as family members of the employees or of the Investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
The two co-primary efficacy endpoints of the study (that will be analysed according to a hierarchical approach) are: • Change in baseline of (mean) POM reduction after 3 days of DHEP 2.6% medicated plaster is greater than placebo (vehicle) plaster. • Change in baseline of (mean) POM reduction after 3 days of DHEP 2.6% medicated plaster is no worse than the comparator Flector®. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Baseline line Day 0 to Day 3 Included |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints of the study will be the comparisons between treatment groups of the following parameters: POM at in-clinic visits, POM day-by-day, evaluation of peri-malleolar oedema, affected ankle joint function, rescue medication consumption, onset of pain relief, rate of responders (proportion of subjects achieving a 50% POM reduction), overall treatment efficacy. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 15 |