Clinical Trials Register

Summary
EudraCT Number:	2008-004557-15
Sponsor's Protocol Code Number:	08.0278-38
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-09-16
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

Germany - BfArM

A.2

EudraCT number

2008-004557-15

A.3

Full title of the trial

10 days clinical pilot study to investigate the wound healing efficacy of Mirfulan® ointment (containing zinc oxide and cod liver) in an intra-individual comparison with a placebo, zinc oxide and cod liver oil after induction of suction blisters in 22 healthy subjects

A.3.2

Name or abbreviated title of the trial where available

Wound healing efficacy of Mirfulan® ointment in a suction blister model

A.4.1

Sponsor's protocol code number

08.0278-38

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merckle Recordati GmbH
B.1.3.4	Country	Germany
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	Yes
D.2.1.1.1	Trade name	Mirfulan
D.2.1.1.2	Name of the Marketing Authorisation holder	Merckle Recordati GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Ointment
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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.3.9.3	Other descriptive name	ZINC OXIDE
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	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	8001692
D.3.9.3	Other descriptive name	COD-LIVER OIL
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	10
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	Control 1
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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.3.9.1	CAS number	8001692
D.3.9.3	Other descriptive name	COD-LIVER OIL
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	10
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	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	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	Control 2
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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.3.9.3	Other descriptive name	ZINC OXIDE
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	10
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Ointment
D.8.4	Route of administration of the placebo	Topical use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

healthy volunteers

Mirfulan® ointment is a topical formulation for the treatment of wounds. Indications for the application of Mirfulan® are treatment of non-infectious acute and subacute skin damages with erythema, itching and pain.

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 study is to assess the efficacy in wound healing of Mirfulan® ointment in comparison to a placebo and the two ingredients zinc oxide and cod liver oil after induction of wounds (suction blisters). For this purpose TEWL measurements directly after induction of suction blisters will be compared with TEWL measurements at the last study day (day 10). Comparisons between products will be based on a repeated measures ANOVA including one within-subjects factor product.

E.2.2

Secondary objectives of the trial

•Raw TEWL values at each assessment time point. Comparison of all four test formulations.
•Difference from baseline of TEWL for each product and each assessment time point.
•Area under the curve (AUC) for TEWL ranging from day 1 to day 10
•Raw values of size of wound areas at each assessment time point. Comparison of all four test formulations.
•Comparison of wound areas at baseline with all other assessment time points after application (percent changes (reduction) to baseline will be calculated). Comparison of all four test formulations
•Area under the curve for size of wound area ranging from day 1 to day 10
•Safety parameters will be documented and analyzed

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Male or female subjects with healthy skin and skin type I to IV (Fitzpatrick et al. 1974)
•Age 18-55
•Willingness to actively participate in the study and to come to the scheduled visits
•Willingness to discontinue the use of own cleansing and cosmetic products (e.g. soaps, creams, moisturizers) in the treatment areas throughout the course of the study
•Signed written informed consent to participate in the study
•Negative urine pregnancy test (in female subjects of child bearing potential)
•Reliable methods of contraception which result in a low failure rate (i.e. less than 1% per year) for women of childbearing potential (implants, injectables, combined oral contraceptives, some intrauterine-devices, sexual abstinence or vasectomised partner)
•Willingness to avoid extended artificial as well as natural UV light two weeks before the study, during the whole course of the study and at least 3 months after the end of the study
•Willingness to avoid swimming or sauna as well as extreme sporting until the complete re-epithelization of the wounds
•Uniform skin color with no erythema in the test area

E.4

Principal exclusion criteria

•Medication

-Systemic treatment with drugs interfering with the immune system:
Corticosteroids, antibiotics 30 days prior to study day 1 and during conduct of study
Antihistamines 30 days prior to study day 1 and during conduct of study
Immunosuppressants 30 days prior to study day 1 and during conduct of study
Antiphlogistics
(minor pain relief medicine like acetaminophene if not more than 1000 mg per day is allowed) 30 days prior to study day 1 and during conduct of study

-Systemic treatment with substances affecting blood coagulation
Acetylsalicylic acid 10 days prior to study day 1 and during the 10 days of the study
Anticoagulants 30 days prior to study day 1 and during conduct of study
Diuretics 30 days prior to study day 1 and during conduct of study

-Topical treatment of test areas*:
Corticosteroids, antibiotics 2 weeks prior to study day 1 and during conduct of study
Anti-inflammatory substances 2 weeks prior to study day 1 and during conduct of study
Pretreatment with any of the test preparations tested in this study 30 days prior to study day 1 and during conduct of study
* moisturizers and sun protection are allowed until 3 days prior to study day 1 but not during the conduct of the study

•Diseases

Atopic dermatitis, eczema and/or sensitive, very dry skin
Active skin disease, e.g. skin tumors
Moderate or severe illness within the last two weeks before first exposure
Known infectious diseases (e.g. hepatitis or AIDS)

•Known hypersensitivity against:
Wool wax alcohol
Hamamelis
Glycerolmonostearate
Other ingredients of the test products
Plaster

•History of keloids and hypertrophic scars
•TEWL before induction of suction blisters > 12 g/m2/h
•pregnancy or lactation
•moles, tattoos, pigmentation or scars on the forearm that would influence the visual scoring
•intensive UV-light exposure within two weeks before the beginning of the test as well as during the study
•psychiatric conditions that might limit the participation in the trial and/or that lead to the assumption that the ability to completely understand the consequences of consent is missing
•any history of drug addiction or alcoholism in the past 3 years
•any history of severe illnesses in the past 3 years
•subjects with poor compliance
•participation in a clinical trial within the last 30 days prior to the start of this study
•subjects underlying any other restrictions due to the participation in other tests / test institutes
•employees of the study sites or of the Sponsor’s company

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint:
Comparison of test products based on differences in TEWL (day 10 – day 1)
Secondary endpoints:
Comparison of test products based on TEWL at each assessment timepoint (difference to baseline)
Comparison of test products based on wound area at each assessment timepoint (% changes from baseline)
Comparison of test products based on AUC (TEWL, Wound area)
Comparisons to baseline for each test product (TEWL, Wound area raw data)

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

Information not present in EudraCT

E.7.1.2

Bioequivalence study

Information not present in EudraCT

E.7.1.3

Other

Information not present in EudraCT

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

same as IMP but with only one active substance each

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

Information not present in EudraCT

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

end of the study is the last visit of the last subject

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 days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2008-09-16.

Yes

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)

Since only subjects with healthy skin will be enrolled in this study, a treatment after study termination is not foreseen. In case of incomplete wound healing a follow-up visit will be arranged until a stable condition of the wound is achieved.

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

2008-10-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-11-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2008-11-28

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