metabolite, AR-13503, were eva luated in 18 healthy subjects after topical ocular administration of RHOPRESSA 0.02% once daily (one drop bilaterally in the morning) for 8 days. There were no quantifiable plasma concentrations of netarsudil (lower limit of quantitation (LLOQ) 0.100 ng/mL) post dose on Day 1 and Day 8. Only one plasma concentration at 0.11 ng/mL for the active metabolite was observed for one subject on Day 8 at 8 hours post-dose.
Metabolism
After topical ocular dosing, netarsudil is metabolized by esterases in the eye.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have not been performed to eva luate the carcinogenic potential of netarsudil. Netarsudil was not mutagenic in the Ames test, in the mouse lymphoma test, or in the in vivo rat micronucleus test. Studies to eva luate the effects of netarsudil on male or female fertility in animals have not been performed.
14 CLINICAL STUDIES
RHOPRESSA 0.02% was eva luated in three randomized and controlled clinical trials, namely AR-13324-CS301 (NCT 02207491, referred to as Study 301), AR-13324-CS302 (NCT 02207621, referred to as Study 302), and AR-13324-CS304 (NCT 02558374, referred to as Study 304), in patients with open-angle glaucoma or ocular hypertension. Studies 301 and 302 enrolled subjects with baseline IOP lower than 27 mmHg and Study 304 enrolled subjects with baseline IOP lower than 30 mmHg. The treatment duration was 3 months in Study 301, 12 months in Study 302, and 6 months in Study 304.
The three studies demonstrated up to 5 mmHg reductions in IOP for subjects treated with RHOPRESSA 0.02% once daily in the evening. For patients with baseline IOP < 25 mmHg, the IOP reductions with RHOPRESSA 0.02% dosed once daily were similar to those with timolol 0.5% dosed twice daily (see Table 1). For patients with baseline IOP equal to or above 25 mmHg, however, RHOPRESSA 0.02% resulted in smaller mean IOP reductions at the morning time points than timolol 0.5% for study visits on Days 43 and 90; the difference in mean IOP reduction between the two treatment groups was as high as 3 mmHg, favoring timolol.
Table 1: Mean IOP Change from Baseline of Study Eye (mmHg) by Visit and Time
Study 301: Subjects with Baseline IOP < 25 mmHg Study 301: Subjects with Baseline IOP >= 25 and < 27 mmHg
Study 302: Subjects with Baseline IOP < 25 mmHg Study 302: Subjects with Baseline IOP >= 25 and < 27 mmHg
Study 304: Subjects with Baseline IOP < 25 mmHg Study 304: Subjects with Baseline IOP >= 25 and < 30 mmHg
This table was produced based on the observed data from all randomized subjects who did not have major protocol violations. The treatment differences and two-sided CIs for comparing Rhopressa QD vs Timolol BID 0.5% were based on Analysis of Covariance (ANCOVA) adjusted for baseline IOP.
16 HOW SUPPLIED/STORAGE AND HANDLING
RHOPRESSA® (netarsudil ophthalmic solution) 0.02% (0.2 mg per mL) is supplied sterile in opaque white low density polyethylene bottles and tips with white polypropylene caps.
2.5 mL fill in a 4 mL container
NDC # 70727-497-25
