Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Ophtalmologicals, other ophtalmologicals, ATC code: S01XA21.

Mechanism of action
Cysteamine reduces corneal cystine crystal accumulation acting as a cystine-depleting agent by converting cystine to cysteine and cysteine-cysteamine mixed disulfides.

Clinical efficacy and safety
Two clinical trials were performed with Cystadrops: a single arm clinical trial on 8 children and adults (OCT-1 study) and a randomised, multi-centre, open label, active controlled phase III clinical trial (CHOC study) conducted on 32 patients.

OCT-1 study
This study assessed the safety and efficacy of Cystadrops during 5 years. Dose adaptation was performed following ocular examination. None of the patients discontinued treatment over the 5 year follow-up.
The efficacy was assessed with In-Vivo Confocal Microscopy total score (IVCM score) by quantifying the cystine crystals in the 7 layers of the cornea. After 30 days of treatment and at a median frequency of 4 instillations per day, an average 30% decrease in the IVCM total score was observed. A mean decrease in corneal cystine crystal deposits of 30%, in comparison with baseline, was maintained over time with a median dosing regimen of 3 drops/eye/day (range 1-3 drops) for 7 of the 8 patients. Photophobia tended to improve over time.

CHOC study
This study was a randomised, controlled trial to assess the efficacy and the safety profile of Cystadrops following a period of 90 days of treatment at a dose regimen of 4 drops/eye/day. The IVCM total score was the primary efficacy endpoint. 15 patients were exposed to Cystadrops. The mean IVCM total score was calculated for 11 patients. A trend towards a lower IVCM total score in Cystadrops arm was observed at day 30. The mean decrease by 40% in the Cystadrops arm was confirmed at day 90. Superiority of Cystadrops was demonstrated compared to the control arm (cysteamine hydrochloride 0.10%) p<0.001 95% CI (2.11; 5.58). Superiority of Cystadrops was also demonstrated for photophobia rated by the investigator compared to the control arm (cysteamine hydrochloride 0.10%) p< 0.048 95% CI (0.23; 1.14).

Paediatric population
Clinical data on safety and efficacy were collected during the 2 clinical trials (OCT-1 and CHOC studies). In total 15 paediatric patients were exposed to Cystadrops whereof 3 subjects (including one 2 year and one 3 year old subject) being less than 6 years of age. The efficacy and safety results are similar in both paediatric and adult populations.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties
Human pharmacokinetic assessment following ocular administration of Cystadrops was not performed.

Similarly to other topically administered ocular products, systemic absorption is likely to occur.
However it should be considered that the recommended daily dose of cysteamine applied as eye drops is no more than approximately 0.4% of the highest recommended daily oral dose of cysteamine in any age group.