Clinical Trials Register

Summary
EudraCT Number:	2017-003526-32
Sponsor's Protocol Code Number:	EQI7-16-02
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-01-29
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2017-003526-32

A.3

Full title of the trial

Randomised, 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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical trial with Diclofenac Sodium 140 mg medicated plaster in patients with impact injuries of the limbs

A.3.2

Name or abbreviated title of the trial where available

Not available

A.4.1

Sponsor's protocol code number

EQI7-16-02

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fidia Farmaceutici S.p.A.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Fidia Farmaceutici S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	LB Research S.r.l.
B.5.2	Functional name of contact point	Flavia Baruzzi
B.5.3	Address:
B.5.3.1	Street Address	Via Lombardia 81
B.5.3.2	Town/ city	Cantù
B.5.3.3	Post code	22063
B.5.3.4	Country	Italy
B.5.4	Telephone number	0039031734908
B.5.5	Fax number	00390317372218
B.5.6	E-mail	flavia.baruzzi@lbresearch.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Diclofenac sodium 140 mg medicated plaster
D.3.2	Product code	EQI7
D.3.4	Pharmaceutical form	Medicated plaster
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DICLOFENAC SODIUM
D.3.9.1	CAS number	15307-79-6
D.3.9.2	Current sponsor code	EQI7
D.3.9.3	Other descriptive name	DICLOFENAC SODIUM
D.3.9.4	EV Substance Code	SUB01674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	140
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Flector 180 mg cerotto medicato
D.2.1.1.2	Name of the Marketing Authorisation holder	IBSA Farmaceutici Italia Srl
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Diclofenac epolamine
D.3.4	Pharmaceutical form	Medicated plaster
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DICLOFENAC EPOLAMINUM
D.3.9.3	Other descriptive name	DICLOFENAC EPOLAMINE
D.3.9.4	EV Substance Code	SUB20558
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Medicated plaster
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patients with painful and phlogistic (inflammatory response) disease due to acute traumatic events (injury/contusion) of the limbs

E.1.1.1

Medical condition in easily understood language

Patients with painful injury/contusion of the limbs

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this trial is to show non-inferior efficacy of Test Diclofenac Sodium 140 mg medicated plaster (once a day) over a Reference Diclofenac epolamine (DIEP) 180 mg medicated plaster, Flector® (once a day), and that both Test and Reference are superior to Placebo plaster (once a day) in improving pain at rest at 72 ± 2 hours (Day 4) after treatment start in patients with painful and phlogistic (inflammatory response) disease due to acute traumatic events (injury/contusion) of the limbs. A 100-mm Visual Analogue Scale (VAS) will be used for the assessment of pain at rest.

E.2.2

Secondary objectives of the trial

The secondary objectives of the clinical trial are to evaluate:
• The efficacy of the Test product in comparison to Reference and Placebo with regard to pain relief (pain at rest and pain on movement), consumption of rescue medication and global assessment of efficacy by patient;
• The adhesion of the Test product in the site of application in comparison to Reference and Placebo;
• The general safety and local tolerability of the Test product in comparison to Reference and Placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients who meet all of the following criteria will be enrolled in the study:
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.

E.4

Principal exclusion criteria

Patients who fulfil any of the following criteria will not be enrolled in the study:
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 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

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in VAS score for pain at rest at 72 ± 2 hours (Day 4) after treatment start.

E.5.1.1

Timepoint(s) of evaluation of this end point

72 hours ± 2 hours after treatment start

E.5.2

Secondary end point(s)

Efficacy parameters
• Area under the curve (AUC) for pain at rest at Day 4 and Day 8 (SPID0-4d and SPID0-8d);
• Change from baseline of VAS for pain at rest at the other study time-points (including patients’ home measurements);
• Time to resolution of pain at rest;
• Change from baseline in VAS score for pain on movement at 72 ± 2 hours (Day 4) and at 192 ± 2 hours (Day 8) after treatment start;
• Proportion of responder patients (defined as a decrease ≥ 50% of baseline VAS for pain at rest and on movement) at 72 ± 2 hours (Day 4) after treatment start;
• Proportion of patients that will use rescue medication (paracetamol) and consumption of rescue medication during the entire study period;
• Global assessment of efficacy by patient, performed at 72 ± 2 hours (Day 4) and at 192 ± 2 hours (Day 8) after treatment start;
• Assessment of the adhesion of the medicated plaster IMP in the site of application, performed daily by patients and at 72 ± 2 hours (Day 4) and at 192 ± 2 hours (Day 8) after treatment by the “open” member of the staff.
Safety parameters
• Summaries of adverse events (AEs) and frequency of discontinuation of treatment due to AEs;
• Local tolerability (erythema, itching, burning and local pain) at the IMP application site;
• Investigator’s and patient’s opinion on local tolerability;
• Change from baseline in vital signs (blood pressure and heart rate);
• Abnormalities in the physical examination.

E.5.2.1

Timepoint(s) of evaluation of this end point

It depends on the endpoint considered. See previous section.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

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

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

LPLV

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

205

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

210

F.4.2.2

In the whole clinical trial

210

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-04-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-03-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-10-27

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