Clinical Trials Register

Summary
EudraCT Number:	2015-001779-29
Sponsor's Protocol Code Number:	EP-DICLO/G-01-2015
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-10-20
Trial 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

2015-001779-29

A.3

Full title of the trial

Randomized, double-blind, parallel group, placebo-controlled, multicenter clinical trial to evaluate efficacy and safety of diclofenac 1% gel produced by Epifarma s.r.l. (Test) versus the originator Voltaren® Emulgel® 1% gel taken as Reference

A.3.1

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

Multicenter clinical trial to evaluate efficacy and safety of diclofenac 1% gel produced by Epifarma s.r.l. compared to Voltaren® Emulgel® 1% gel

A.4.1

Sponsor's protocol code number

EP-DICLO/G-01-2015

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	Epifarma s.r.l.
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	Epifarma s.r.l.
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	Bitrial Clinical Research
B.5.2	Functional name of contact point	János Bíró
B.5.3	Address:
B.5.3.1	Street Address	Tállya utca 23.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1121
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3618008036
B.5.5	Fax number	+3618008037
B.5.6	E-mail	janos.biro@bitrial.hu

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 1% gel
D.3.4	Pharmaceutical form	Gel
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 Diethylamine
D.3.9.1	CAS number	78213-16-8
D.3.9.3	Other descriptive name	DICLOFENAC DIETHYLAMINE
D.3.9.4	EV Substance Code	SUB01669MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	Voltaren Emulgel® 1% gel
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Farma S.p.A.
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.3.4	Pharmaceutical form	Gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous use
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	Gel
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 acute painful and flogistic (inflammatory) disease due to acute traumatic events (injury/contusion) of joints, muscles, tendons and ligaments

E.1.1.1

Medical condition in easily understood language

Patients with injury/contusion of joints, muscles, tendons and ligaments

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 the trial is to demonstrate that the Test diclofenac 1% gel produced by Epifarma s.r.l. is non-inferior to the comparator Voltaren® Emulgel® 1% gel, and that both Test and Reference are superior to Placebo gel, in improving pain at rest in patients with acute painful and flogistic (inflammatory) disease due to acute traumatic events (injury/contusion) of joints, muscles, tendons and ligaments over a treatment of maximum 1 week.

E.2.2

Secondary objectives of the trial

• Time to resolution of pain at rest;
• VAS for pain at rest at the other time points, including the area under the curve (AUC) from baseline up to 96 ± 4 hours;
• Proportion of responder patients at 96 ± 4 hours and at the end of the study;
• VAS for pain on movement measured at any time point;
• Proportion of patients that will use rescue medication and consumption of rescue medication (paracetamol) at 96 ± 4 hours and at the end of the study;
• Global assessment of efficacy by investigator;
• Tolerability and safety of the IMPs, assessed through summaries of adverse events, the frequency of discontinuation of treatment due to adverse events, vital signs (sitting heart rate, systolic/diastolic blood pressure, respiratory rate, body temperature), erythema at the IMP application site, and physical examination.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients aged 18-65 years;
2. Patients with acute painful and flogistic (inflammatory) disease due to acute traumatic events (injury/contusion) of joints, muscles, tendons and ligaments);
3. Patient with pain at rest in only one body surface area affected by injury/contusion;
4. Presence of mild to moderate pain at rest, defined as a scored VAS ≥ 20 mm and ≤ 60 mm, in the injured area;
5. Female and 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 administration;
6. Satisfactory general health status as determined by the investigator based on medical history and physical examination;
7. Patients must understand and provide written informed consent before they can participate in the study. He/she must understand the study procedures of the trial, and be willing to complete the required assessments.

E.4

Principal exclusion criteria

1. Patient unwilling to give an informed consent approval;
2. Patient with presence of pain at rest in more than one body surface area affected by the injury/contusion;
3. Patient with a chronic painful or flogistic disease (from more than three months);
4. Patient with painful or flogistic (inflammatory) disease arising from fractures or severe trauma events;
5. Pregnancy or lactation period throughout the whole study duration;
6. If female and of child-bearing potential, patient not using a highly effective method of birth control. Highly effective birth control methods include: combined (estrogen and progestogen containing) hormonal contraception 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*;
7. Presence of concurrent skin disorders or open wounds in the area to be treated;
8. History of alcohol or drug abuse;
9. History of allergy or hypersensitivity or intolerance to diclofenac and/or to active or inactive excipients of formulation;
10. Known hypersensitivity to non-steroid anti-inflammatory drugs, and in particular to paracetamol;
11. Use of non-steroid anti-inflammatory drugs (e.g. acetyl salicylic acid) and analgesics (with the exception of paracetamol) in the week before the study. Chronic intake of small doses of acetylsalicylic acid (≤ 162 mg/daily) taken for at least 30 days prior to the first dose of study medication for non-analgesic reasons may be continued for the duration of the study;
12. 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, opioids, psychotropic agents, anti H1 agents or analgesics like glucocorticosteroids, NSAIDs, etc.) in the week before the study;
13. Any other concomitant treatment (e.g. cosmetics, ointments at the treated area) or medication that can't be interrupted and interferes with the conduct of the trial;
14. History of active or suspected esophageal, gastric, pyloric channel, or duodenal ulceration or bleeding within 30 days preceding screening;
15. History of uncontrolled chronic or acute concomitant disease which, in the Investigator’s opinion, would contraindicate study participation or confound interpretation of the results;
16. Participation in any other clinical study within 30 days prior to the screening.

*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 (43).

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in VAS score for pain at rest 96 ± 4 hours after treatment start

E.5.1.1

Timepoint(s) of evaluation of this end point

96 ± 4 hours after treatment start

E.5.2

Secondary end point(s)

Efficacy
• Time to resolution of pain at rest;
• VAS for pain at rest at the other time points, including the AUC from baseline up to 96 ± 4 hours;
• Proportion of responder patients at 96 ± 4 hours and at the end of the study. A responder patient is defined as a patient with a decrease of pain at rest ≥ 50% vs. the baseline value;
• VAS for pain on movement measured at any time point;
• Proportion of patients that will use rescue medication and consumption of rescue medication (paracetamol) during the first 96 ± 4 hours and over the entire study;
• Global assessment of efficacy by investigator.
Safety
• Summaries of adverse events (AEs) and frequency of discontinuation of treatment due to AEs;
• Vital signs (sitting heart rate, systolic/diastolic blood pressure, respiratory rate, body temperature);
• Erythema at the IMP application site;
• Physical examination

E.5.2.1

Timepoint(s) of evaluation of this end point

See point E.5.2

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

Yes

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

This trial is considered closed when all e-CRFs are satisfactorily completed and the database is finally locked.

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:

749

F.1.3

Elderly (>=65 years)

Yes

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

300

F.4.2

For a multinational trial

F.4.2.1

In the EEA

749

F.4.2.2

In the whole clinical trial

749

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)

The Study medication will not be available to patients after the study termination or prematurelywithdrawn from the study. Follow-up Treatment within the scope of the study is not planned, patients will be treated according to the investigator's judgement.

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

2016-12-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-11-23

P. End of Trial
P.	End of Trial Status	Ongoing

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