Registration Dossier

Administrative data

Endpoint:
sensitisation data (humans)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 08 - December 17, 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted in consideration of internationally recognized guidelines and procedures for Good Clinical Practice (GCP). Limited information about substance identity: no purity and no batch number.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Type of sensitisation studied:
skin
Study type:
study with volunteers
Test guideline
Qualifier:
according to
Guideline:
other: Internationally recognized guidelines and procedures for Good Clinical Practice (GCP) and of the German Drug Law and the GCP/EC-Note of Guidance of the CPMP (GCP/EG - Note of Guidance "GCP for Trials on Medicinal Products in the EU", Doc. III/3976/88).
Deviations:
yes
Remarks:
see Princilpes of method
Principles of method if other than guideline:
Protocol deviations:
Pretest and Induction were started on the same day, because of saving time and respect to the fact, that skin irritation was very unlikely considering the chemical structure of the test item. Patches for pretest and induction were applied on different spots of back or upper arm and the patch for pretesting was read for up to 72 hours after patch removal. The 72 hours reading of the challenge test was dispensed in the interest of the volunteers because of no skin reactions at all throughout the testing period.
GLP compliance:
no
Remarks:
but, GCP compliant

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):RADIAGREEN RA

Method

Type of population:
other: Adult male and female Caucasian volunteers
Ethical approval:
other: not necessary in respect to the nature of the test item and the testing procedure.
Subjects:
- Number of subjects exposed: 35
- Sex: 24 females and 11 males
- Age: 48 ± 12 years
- Race: Caucasian
- Demographic information: no data available
Clinical history:
Exclusion criteria:
- history of unknown local or systemic allergic reactions
- allergic reactions to plasters,
- intake of antiallergic or anti-imflammatory drugs during the last 2 weeks
- moderate or severe illness within the last 2 weeks before first exposure
- imflammatory, eczematous or any other clinical sign of skin alterations on possilbe test sites
- hyperpigmentation and multiple liver spots (lentigines)on possible test sites
- pregnancy and lactation
- inability to give informed consent or unwillingness to participate.
Controls:
Vaselinum album DAB6 was applied under identical conditions as negative control at the first application.
Route of administration:
dermal
Details on study design:
TYPE OF TEST(S) USED: patch test

ADMINISTRATION
- Type of application: occlusive
- Description of patch: FINN Chambers on Scanpore ® large
- Vehicle / solvent: not applicable
- Concentrations: 100% (pre-test and main test)
- Volume applied: approx. 50 mg
- Testing/scoring schedule:
Pretest:
Testing of irritant properties by applying the test items once for 48 hours (Mo.).
Main test:
Induction phase: Induction of possible sensitization by applying the test items 9 times (3-times weekly on Monday, Wednesday and Friday for 3 weeks) for 48 hours to the same spot on the upper back or arm.
Challenge: Proving of sensitization after an interval of 10 to 14 days by one challenge application (48 hours) of the test items on a naive site.
Readings:
For irritation: immediately, 24 and 48 hours after patch removal.
During induction: immediately after each patch removal (except Friday patch)
For challenge: immediately, 24 and 48 hours after patch removal

EXAMINATIONS
- Grading/Scoring system:
Readings had to be recorded on the CRF and graded in a five point scale as follows:
0 = negative (no reaction)
1 = weak reaction (well defined erythema)
2= moderate reaction (erythema with slight to moderate edema)
3 = strong reaction (vesicles or papules)
4 = extreme reaction (bullous, spreading or other severe reaction)
- Statistical analysis:
All results are analyzed descriptively and exploratively. Means and standard deviations are calculated where applicable. Intraindividual comparisons between the reactions to test items and controls are done by analysis of variance methods for each assessment time; in addition, pairwise comparison is done with the signed Wilcoxon test.
Appropriate statistical methods are applied for comparison of frequency of reactions (e.g. Cochran's Q-test, Mc Nemar test.)

Results and discussion

Results of examinations:
SYMPTOMS
- Frequency, level, duration of symptoms observed: 0

NO. OF PERSONS WITH/OUT REACTIONS COMPARED TO STUDY POPULATION
- Number of subjects with positive reactions: 0
- Number of subjects with negative reactions: 35
- Number of subjects with equivocal reactions: 0
- Number of subjects with irritating reactions: 0

Applicant's summary and conclusion

Conclusions:
In a human repeat patch test, conducted in consideration of internationally recognized guidelines and procedures for Good Clinical Practice (GCP), it can be concluded that there is no or only a minimal risk of skin sensitization when RADIAGREEN is coming in contact with human skin.