Effectiveness and long-term safety of repeated oral administrations of molidustat in the management of anemia associated with chronic kidney disease in cats.

Abstract

BACKGROUND: Erythropoietic effects of molidustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, occur in anemic cats with chronic kidney disease (CKD). HYPOTHESIS/OBJECTIVES: To evaluate the effectiveness and safety of molidustat in managing anemia in cats with CKD. ANIMALS: Seventy-five client-owned anemic cats with CKD in the effectiveness and safety phase and 64 in the safety continuation phase. METHODS: Multicenter, randomized, double-masked, placebo-controlled field study. Cats in the 28-day effectiveness and safety phase received 5&#xa0;mg/kg of molidustat (n&#xa0;=&#xa0;40) or a control product (CP; n&#xa0;=&#xa0;35), once daily for 28 days. During the 20-week safety continuation phase, all cats received 5&#xa0;mg/kg molidustat in 28-day treatment cycles once PCV declined to <&#x2009;28%. Individual cat treatment success, defined as a&#xa0;&#x2265;&#xa0;4% point increase in hematocrit (HCT) compared to baseline, was evaluated on day 28. Safety was assessed throughout both phases. RESULTS: Proportion of molidustat-treated cats with treatment success on day 28 (68%&#xa0;&#xb1;&#xa0;7.4%; 95% CI, 51.45-80.28) was significantly higher compared to CP cats (17%&#xa0;&#xb1;&#xa0;6.4%; 95% CI, 7.80-33.59; P&#xa0;<&#xa0;.001). During the safety continuation phase, median treatment cycle duration was 28&#xa0;days with treatment intermission medians ranging from 11 to 18&#xa0;days. There was no evidence of adverse effects attributed to molidustat when administered alone or in combination with other medications. CONCLUSIONS AND CLINICAL IMPORTANCE: Molidustat significantly increased HCT values in treated cats compared to CP cats. Repeated 28-day treatment cycles were well-tolerated. Molidustat is an effective and safe treatment for long-term management of anemia in cats with CKD.