Safety of once daily ilunocitinib tablets in healthy dogs

Abstract

BACKGROUND: Ilunocitinib is a new molecular entity of the Janus kinase inhibitor (JAKi) class for the treatment and control of symptoms of allergic skin disease conditions, such as pruritus and skin lesions in dogs. This laboratory study with ilunocitinib tablets (Zenrelia™, Elanco) investigated the safety in healthy dogs treated once daily for 6 months. The study was a randomized, blinded, parallel-group design examining one (1X), two (2X), three (3X) and five (5X) times the maximum recommended dose (0.8 mg/kg) compared to sham dosed control dogs. METHODS: Twenty male and 20 female healthy Beagle dogs, 11 to 12-month of age, with a mean body weight ranging from 9.85 to 10.46 kg, were randomized to an untreated control group or ilunocitinib treatment groups at daily dose rates of 0.8 mg/kg (1X), 1.6 mg/kg (2X), 2.4 mg/kg (3X), or 4.0 mg/kg (5X) over six months. All animals were fed within 30 min prior to treatment. Safety assessments included general health observations, clinical observations (including complete physical and neurological examinations), ophthalmology, clinical pathology, peripheral blood immunophenotyping, body weight, food consumption, pharmacokinetic blood collections, organ macroscopic and microscopic examinations. RESULTS: No effects of the treatment were noted on body weight, food consumption, physical and neurological examinations, urinalysis, peripheral blood immunophenotype, and ophthalmoscopic examinations. Clinical findings included non-exudative skin lesions, skin lesions with discharge, swollen paw(s), skin thickening, skin discoloration or scabbing of the feet (paws/digits), in both male and female dogs. Changes in clinical pathology included marginally decreased red cell mass, lower eosinophils, higher C-reactive protein, total protein and fibrinogen, lower albumin and albumin: globulin levels. Microscopic findings included skin inflammation and focal dermatitis/furunculosis. CONCLUSIONS: Ilunocitinib was well tolerated when administered daily over six months at 0.8 mg/kg and multiples thereof up to 4.0 mg/kg in Beagle dogs. At the therapeutic dose, no clinically significant changes were observed. Minimal changes in hematological parameters, total protein, and fibrinogen were noted at the higher doses. All of these findings, consistent with the known pharmacology of the JAKi class at exaggerated dosing, support the safe and chronic use of Zenrelia™ tablets. CLINICAL TRIAL NUMBER: Not applicable.