Toleriane Ultra Reno in Allergic Subjects With Skin Intolerance to Their Usual Cosmetic

The evaluation of Toleriane Ultra in allergic subjects having skin intolerance to their usual cosmetic care has been conducted under cosmetic form and dermatological control by Dermscan that is certified by the International Standards Organization (ISO) 9001-2015.

Each study report is subjected to a quality inspection by a member of Dermscan. A certificate of quality inspection signed by a proofreader (not involved in the audited study) is enclosed in each study. The inspection of the study report allows to confirm that the results reflect exactly the study raw data and that the study fulfills any standard and regulatory requirements.

With regard to the statistical analysis, the continuous data is summarized using the following statistics by time point (Day0, Day14, Day28): number of values, mean, median, standard deviation, minimum value, maximum value. For each continuous data obtained from devices (Tewameter for Transepidermal water loss, Corneometer for cutaneous hydration measurements), a mixed linear model for repeated measurements is adjusted to raw data, including the factor "time" as fixed (with 3 levels: Day0, Day14, Day28) and the factor "subject" as random. Using the adjusted means obtained from this model (LS-Means), the contrast of interest is built to assess the change from baseline (Day0) at each point (Day14 and D28). For the categorical data, the global tolerance scores by both the investigator and the participant assessed using a 4-point scale are summarized in frequency (N) and percentage (%) by time point (Day14, D28) with associated 95% confidential interval. For other categorical data, a Wilcoxon signed rank test is carried out for each parameter assessed using an ordinal scale:

• Sensiscore (erythema, irritation, stinging, itching, burning, tightening, discomfort) assessed using a 5-point structured scale of frequency and intensity of the functional signs.
• Composite score of the skin state (redness, pruritus, dryness, burning sensation, tingling) assessed using a 4-point structured scale.
• Smoothing effect assessed using a 4-point structured scale.

The participants have the right to exit from the study at any time and for any motive, in compliance with the Helsinki Declaration (1964) and its successive updates. The investigator can also interrupt the person's participation in the study prematurely in the case of a disease occurrence, a pregnancy or the occurrence of an adverse reaction.

Every premature exit must be classified under one of the following headings:

• presence of non-inclusion criteria;
• Undesirable Effect / Adverse Event occurrence;
• Serious Adverse Event / Serious Adverse Effect occurrence;
• withdrawal of consent;
• lost to follow-up;
• the appearance of non-inclusion criteria;
• non-adherence to the protocol;
• other reason.

All the adverse events and serious adverse events are reported in the case report form and the study report.

No replacement is foreseen as 10% additional participants are planned to be included in the study (110 included participants in order to obtain results on 100 (+/- 10%) participants minimum.). An identification code is attributed to each participant for the purpose to keep his/her identity confidential.

The personnel in charge of the study collects data into individual case report forms in electronic or paper format and/or directly from measurement software. When information is collected in paper format, the double data entry is then done from these supports by the designed operator(s), without any interpretation, in specific EXCEL databases. The Project Manager or assistant checks the double data entry by comparing both databases. Then the coherence of the whole data set is checked as well as formulas used in the EXCEL tables (calculation formulas, selected data…). When all the controls are done, the database is locked.