Regulatory Decision Summary for PAZEO

Benefit
To support the proposed indication of PAZEO (Olopatadine Ophthalmic Solution, 0.77%, once daily) for the treatment of ocular itching associated with allergic conjunctivitis, the sponsor submitted two pivotal conjunctival allergen challenge (CAC) studies (C-10-126 and C-12-053). Since both olopathdine Hydrochloride Ophthalmic Solution 0.1% (PATANOL) and olopatadine Hydrochloride Ophthalmic Solution 0.2% (PATADAY) have been approved in Canada for the treatment of ocular itching associated with allergic conjunctivitis, and efficacy and safety of olopatadine 0.1% and 0.2% for treatment of ocular itching has already been established through extensive environmental studies (i.e. five studies for PATANOL and four studies for PATADAY with a duration ranging between 4 weeks and 12 weeks), the Therapeutic Product Directorate (TPD) considered two CAC studies submitted in this New Drug Submission (NDS) are adequate to evaluate efficacy of this product.

Both pivotal studies (C-10-126 and C-12-053) shared similar study design: multicenter, randomized, double-masked, vehicle controlled, parallel-group. Study C-10-126 included PATADAY and Vehicle as comparators, and Study C-12-053 included PATADAY, PATANOL and Vehicle as comparators. Both studies enrolled patients who were at least 18 years of age with a history of seasonal and/or perennial allergic conjunctivitis. Both studies evaluated the same efficacy endpoints (patient-evaluated ocular itching and redness) for the onset of action and the 24 hours duration of action. The results of these studies consistently showed that PAZEO was superior (statistically and clinically) to Vehicle for treating ocular itching associated with allergic conjunctivitis at onset-of-action, and 24-hour duration-of action. In Study C-10-126, PAZEO demonstrated statistically significant improved relief of ocular itching when compared to PATADAY for 24-hour duration-of-action. In Study C-12-053, PAZEO demonstrated statistically significant improved relief of ocular itching when compared to PATADAY and PATANOL for 24-hour duration-of-action.

The totality of efficacy data demonstrated in two CAC studies for Olopatadine 0.77% in reducing ocular itching, as well as those demonstrated in extensive environmental confirmatory clinical trials for olopatadine 0.1% and olopatadine 0.2%, supports the conclusion that Olopatadine 0.77% dosed once daily is effective for the treatment of ocular itching associated with allergic conjunctivitis.

Risk
The safety profile of PAZEO is primarily derived from a 6-week clinical safety study (C-12-028), in which patients who were at least 2 years of age with asymptomatic eyes at the time of study entry were randomized to receive PAZEO (N=330) or Vehicle (N=169), respectively.

This study included 75 individuals between the ages of 2-17 years of age and 35% were male. The most commonly reported adverse drug reactions with a rate of equal or greater than 1% in either treatment group included blurred vision, abnormal sensation in eye, dry eye, eye irritation, corneal staining, conjunctival staining, and dysgeusia. Less common adverse drug reactions (occurred at an incidence of ≥0.1% to <1%) included eye pain, eye irritation, eye pruritus, ocular hyperaemia, eyelid margin crusting, superficial punctate keratitis, headache, and dry throat. No clinically significant changes were noted in Visual Acuity, Intraocular Pressure, Slit Lamp or Funduscopy in the trial. No overall difference in safety has been observed between pediatric and adult patients.