Both the patients and the investigators in the vast majority judged the global tolerability of verum and placebo “excellent” or “good”. Following dichotomisation of the verbal scale to „yes“ (= favourable) including „excellent“ and „good“ and „no“ (= unfavourable) including „moderate“ and „poor“ no significant difference between verum and placebo for both investigators and patients was detected.
Local tolerability of Diclofenac sodium 4% Spray Gel (DicloFlex®) respectively the vehicle was juged as being excellent. Individual cases of local symptoms as erythema, exanthema, pruritus, or dry skin were reported as also known for other topical NSAIDs. As the incidence is similar in the verum and placebo treatment group it is obvious that these adverse effects cannot be allocated to the active substance. This estimation is confirmed by positive re-exposition reactions with placebo. Clinically irrelevant shifts of laboratory parameters from one category to another were observed in a number of cases. The absence of systemic adverse events is in agreement with the very low plasma levels following the application of Diclofenac sodium 4% Spray Gel (DicloFlex®) as observed in the pharmacokinetic studies mentioned in Module 2.5.3. Patients and investigators rated the global tolerability of the product as good. The reasonable safety profile of Diclofenac sodium 4% Spray Gel (DicloFlex®) which has been documented by this study confirms the expected reduced toxicity of topical NSAIDs compared to oral dosage forms, reported in several other studies.