Título / Title

PK PROFILE OF THE PORT DELIVERY SYSTEM WITH RANIBIZUMAB IN THE PHASE 3 ARCHWAY TRIAL

Introdução / Purpose

PDS with ranibizumab (RBZ) is an investigational drug delivery system for continuous delivery of RBZ into the vitreous. In Archway trial in pts with nAMD, serum and aqueous humor samples were collected to characterize the RBZ pk delivered via the PDS

Material e Método / Methods

In the PDS Q24W and i.v. RBZ Q4W arms, serum pk samples were collected at randomization and at weeks (w) 4, 24, 36, and 96 from all pts. Samples were taken at days 2 and 7 and at w 12, 48, and 72 in the PDS arm, and 1–5 days after an injection in the RBZ arm. The pk-evaluable population included pts who did not receive RBZ as supplemental treat. in the study eye after implant insertion or in the fellow eye, or pts with prior i.v. bevacizumab treat.. Vitreous concentrations were predicted using a population pk model with a compartmental structure, including compartments for the implant, vitreous, and serum, where the dose was either administered into the vitreous or into the implant

Resultados / Results

In PDS Q24W arm (n = 94), geometric mean (CV%) serum RBZ conc. ranged from 419 (54%) pg/mL at week 4 to 340 (94%) pg/mL at week 24. In the RBZ arm (n = 79), the geometric mean serum RBZ conc. ranged from 1880 (57%) pg/mL at 1–5 days after injection (Cmax) to 58.1 (171%) pg/mL at week 4 (Ctrough). The aqueous humor pk profile reflected the same trends seen in serum, with PDS Q24W (n = 42) maintaining concentrations above monthly ranibizumab Ctrough (n = 46). Using a population pk model, in both serum and vitreous, the total RBZ exposure with PDS 100 mg/mL Q24W was predicted to be ~40% of the total RBZ exposure with i.v. RBZ 0.5 mg Q4W injections. The predicted vitreous humor conc. RBZ were estimated to decrease by half by 170 days after a refill

Discussão e Conclusões / Conclusion

PDS continuously released RBZ achieving steady concentrations. RBZ conc. with PDS Q24W were within the range experienced with monthly RBZ injections. The aqueous humor pk was consistent with the serum pk profile

Palavras Chave

Port Delivery System
Ranibizumab
Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents

Area

CLINICAL RETINA