Clinical Trials Register

Summary
EudraCT Number:	2020-002101-25
Sponsor's Protocol Code Number:	FDA02_AIM3
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-08-06
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

Austria - BASG

A.2

EudraCT number

2020-002101-25

A.3

Full title of the trial

A SINGLE CENTER, OPEN-LABEL, CLINICAL STUDY TO EVALUATE THE ABILITY OF DERMAL OPEN FLOW MICROPERFUSION (DOFM) FOR BIOEQUIVALENCE TESTING OF TOPICALLY APPLIED DICLOFENAC SODIUM PRODUCTS IN HEALTHY SUBJECTS

EINE KLINISCHE, EXPLORATIVE STUDIE AN GESUNDEN PROBANDEN UM DIE EIGNUNG DERMALER OFFENER MIKROPERFUSION (DOFM) ZUR UNTERSUCHUNG DER BIOÄQUIVALENZ VERSCHIEDENER ÄUSSERLICH ANGEWENDETER DICLOFENAC-NATRIUMPRODUKTE ZU TESTEN

A.3.1

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

A study to investigate drug concentrations in the skin using a special dermal sampling technique

A.4.1

Sponsor's protocol code number

FDA02_AIM3

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	HEALTH – Institute for Biomedicine and Health Sciences, JOANNEUM RESEARCH Forschungsgesellschaft mbH
B.1.3.4	Country	Austria
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	HEALTH – Institute for Biomedicine and Health Sciences, JOANNEUM RESEARC GesmbHH
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	HEALTH – Institute for Biomedicine and Health Sciences, JOANNEUM RESEARC GesmbHH
B.5.2	Functional name of contact point	Katrin Tiffner
B.5.3	Address:
B.5.3.1	Street Address	Neue Stiftingtalstrasse 2
B.5.3.2	Town/ city	Graz
B.5.3.3	Post code	8010
B.5.3.4	Country	Austria
B.5.4	Telephone number	+433168764121
B.5.6	E-mail	katrin.tiffner@joanneum.at

D. IMP Identification
D.IMP: 1
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 - Diclofenac sodium gel 1%
D.2.1.1.2	Name of the Marketing Authorisation holder	Par Pharmaceutical
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Topical use (Noncurrent)
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.3.9.4	EV Substance Code	SUB01674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
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	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	Yes
D.2.1.1.1	Trade name	Diclofenac Soduim Topical Gel, 1 % - Perrigo New York Inc
D.2.1.1.2	Name of the Marketing Authorisation holder	Perrigo
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Topical use (Noncurrent)
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.3.9.4	EV Substance Code	SUB01674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
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: 3
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	Yes
D.2.1.1.1	Trade name	PENNSAID – diclofenac sodium solution, 2%
D.2.1.1.2	Name of the Marketing Authorisation holder	Horizon Therapeutics USA, INC.,
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Transdermal solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
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.3.9.4	EV Substance Code	SUB01674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Healthy Volunteers

E.1.1.1

Medical condition in easily understood language

Healthy Volunteers

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Equipment and Supplies [E07]

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

Primary Aim 1 Pilot Study: Assess dose-response relationship to define dose for the main study
Primary Aim 1 Main Study: Evaluate the ability of dOFM to assess bioequivalence (BE) between different diclofenac products

E.2.2

Secondary objectives of the trial

Secondary Aim 1 Pilot Study: Test for absence of systemic cross-talk (systemic redistribution)
Secondary Aim 2 Pilot Study: Test for absence of lateral diffusion (cross-talk between adjacent treatment sites)
Secondary Aim 3 Pilot Study: Compare non-equivalent test product with reference product

Secondary Aim 1 Main Study: Monitor systemic cross-talk (systemic redistribution)
To monitor if topically applied diclofenac is absorbed into the
systemic circulation and is redistributed back into the skin, blood
samples and dermal ISF samples from a distant untreated site on
the arm will be taken, to assess its diclofenac concentrations.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Healthy, adult volunteers of age 18 to 65 years (both inclusive).
2. Males or non-pregnant, non-breast feeding females using adequate contraceptive methods or abstinence.
3. Able to read, understand and sign the written informed consent form.
4. Willing to follow the protocol requirements and comply with protocol restrictions.

E.4

Principal exclusion criteria

1. Social habits
a. Smoker who is not willing to refrain from smoking during the in-house visit.
b. History of drug and/or alcohol abuse within one year of start of study as judged by the investigator.
2. Medications: Use of any medications other than hormonal contraceptive, hormone replacement therapy or routine vitamins within the 7 days or 5 half-life periods whichever is longer prior to the initial dose of study medication.
3. Diseases: Presence of any clinically relevant acute or chronic disease, which in the investigator´s opinion might jeopardise subject`s safety, evaluation of results or compliance with the protocol.
4. Any reason, which in the opinion of the investigator, would prevent the subject from safely participating in the study.
5. Any abnormalities found during physical examination or vital signs, unless deemed not clinically significant by the investigator.
6. Clinically significant abnormal laboratory evaluation results, as deemed by the investigator.
7. Clinically significant abnormal 12-lead ECG at screening, as deemed by the investigator.
8. Positive results to the test for hepatitis B antigen or hepatitis C antibodies.
9. Positive HIV test.
10. Positive alcohol breath test.
11. Blood donation within 30 days or significant loss of blood or plasma (more than 550 ml) within 90 days prior to screening.
12. Subjects who have received an investigational drug within 30 days prior to the initial dose of study medication.
13. Known hypersensitivity to diclofenac or any components of the drugs.
14. Tattoos or broken and/or damaged skin and/or scarring at the application areas.
15. Active skin diseases like psoriasis or atopic dermatitis, as judged by the investigator.
16. Subjects prone to keloid or hypertrophic scar formation or any known wound healing disorder.
17. Recent and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.), as judged by the investigator.
18. Not willing to avoid excessive sun exposure, steam baths, sauna, swimming and other strenuous activities for 14 days after Visit 2 to ensure good tissue regeneration.
19. Not willing to refrain from shaving the planned treatment sites or using skin care products on the planned treatment sites for at least 5 days prior to start of Visit 2.
20. Pronounced hairiness on the planned treatment sites that may negatively affect BE testing.
21. Known allergy/hypersensitivity to any of the materials/supplies used during the study.
22. Presence of needle phobia.
23. Not enough space on the thighs for the dOFM probe set-up (

E.5 End points

E.5.1

Primary end point(s)

Pilot Study:
 Skin penetration data:
 Dermal diclofenac concentrations in ISF samples
 Area under the diclofenac concentration-time curves (AUC) in the ISF samples
 Maximum observed diclofenac concentration (Cmax) in the ISF samples in the ISF samples

Main Study:
 Skin penetration data:
o Diclofenac concentrations in ISF samples
o Area under the diclofenac concentration-time curves (AUC)
o Maximum observed diclofenac concentration (Cmax)

E.5.1.1

Timepoint(s) of evaluation of this end point

not applicable

E.5.2

Secondary end point(s)

Pilot Study:
 Skin penetration data:
o Diclofenac concentrations in ISF samples
o Diclofenac concentrations in blood samples
o Area under the diclofenac concentration-time curves (AUC)
o Maximum observed diclofenac concentration (Cmax)

Main Study: Secondary Endpoints
The following additional endpoints were selected to enable the evaluation of the Secondary Aims (see section 2):

• Systemic diclofenac concentration
o Concentrations in the blood samples
o Area under the diclofenac concentration-time curves (AUC) in the blood samples
o Maximum observed diclofenac concentration (Cmax) in the blood samples
• Dermal PK profile of the untreated test sites:
o Dermal concentrations in ISF samples
o Area under the diclofenac concentration-time curves (AUC) in the ISF samples
o Maximum observed diclofenac concentration (Cmax) in the ISF samples

E.5.2.1

Timepoint(s) of evaluation of this end point

not applicable

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

Yes

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)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

Yes

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

LVLS

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

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:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

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.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)

Post trial treatment is not applicable

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

2020-09-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-07-30

P. End of Trial
P.	End of Trial Status	Completed

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