Aceclidine

There are no adequate and well controlled studies of aceclidine administration in pregnant women to inform a drug associated risk. In animal reproduction studies, oral administration of aceclidine to pregnant rats and rabbits throughout organogenesis and lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant doses.

There is no information regarding the presence of aceclidine or its metabolite in human or animal milk, the effects on breastfed infants or the effects on milk production to inform the risk of aceclidine to an infant during lactation.

Systemic levels of aceclidine and its metabolites following topical ocular administration are low, and it is not known whether measurable levels of aceclidine or its metabolites would be present in human milk following topical ocular administration.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for aceclidine and any potential adverse effects on the breastfed child from aceclidine or from the underlying maternal condition.

Carcinogenesis

Long term studies in animals have not been performed to evaluate carcinogenic potential.

Mutagenesis

Aceclidine did not show any potential to cause genetic toxicity in a series of studies that included: 1) bacterial assays (Salmonella and E. coli) for reverse gene mutations; 2) an in vitro chromosome aberration assay in cultured human peripheral blood lymphocytes; and 3) an in vivo chromosome aberration assay (micronucleus test) in mice.

Impairment of Fertility

Oral administration of aceclidine produced no adverse effect on fertility in rats at doses up to 1.5 mg/kg/day (approximately 25 times the MRHOD based on body surface area).

Clinical trials experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Aceclidine dosed once daily was evaluated for safety and efficacy in 466 participants with presbyopia in 2 randomized, double-masked, controlled phase 3 studies for 42 days (CLARITY-1, NCT05656027 and CLARITY-2, NCT05728944). Aceclidine dosed once daily was also evaluated for long term safety in 217 participants with presbyopia in a separate randomized, double-masked, controlled phase 3 study (CLARITY-3, NCT05753189) for a 6-month duration.

The most common reported adverse reactions of participants were instillation site irritation (20%), dim vision (16%), and headache (13%). Adverse reactions reported in >5% of participants were conjunctival hyperemia (8%) and ocular hyperemia (7%). The majority of adverse reactions were mild, transient, and self-resolving.