Efficacy evaluation of a new oral chewable tablet containing fluralaner, moxidectin, and pyrantel (BRAVECTO® TriUNO) against hookworm and Toxascaris leonina infections in a non-terminal study design in dogs

Abstract Background Broad-spectrum combination products with efficacy against endo- and ectoparasites offer the potential to optimize owner adherence to expert recommendations for canine antiparasitic treatments. In the development program for a chewable tablet containing fluralaner, moxidectin, and pyrantel, a non-terminal study design was implemented to determine anthelminthic efficacy. Four laboratory studies assessed the efficacy of this investigational veterinary product (IVP) against adult hookworms and adult Toxascaris leonina . Methods In four single-site, non-terminal dose confirmation studies, dogs were inoculated with third-stage larvae of Uncinaria stenocephala (Studies 1 and 2), Ancylostoma caninum (Study 3), or larvated eggs of T. leonina (Study 4). Using fecal egg counts (FECs) from those infections, dogs were ranked and randomized to groups (Studies 1, 3, and 4, 10 per group; Study 2, 8 per group and treated once orally, on day 0, with the minimum recommended IVP dose (fluralaner 10 mg/kg, moxidectin 0.025 mg/kg, pyrantel 5 mg/kg) ( BRAVECTO ® TriUNO, MSD), or left untreated. Approximately 2 weeks later, both groups in all studies were treated orally with a diagnostic dewormer (DDW) containing emodepside-praziquantel (Profender ® modified-release Tablets for Dogs, Vetoquinol). The primary efficacy objective was determined by counts of expelled worms recovered after DDW treatment. Copro-antigen enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), and FECs were completed at key time points. Results Adequacy of infection was shown in all studies. Relative to the control groups, statistically significant reductions in mean worm counts were found in IVP-treated groups in Studies 1, 2, 3, and 4 (99.8%, P < 0.0001; 100%, P = 0.0002; 100%, P < 0.0001; and 99.4%, P < 0.0001, respectively). All control dogs had positive FECs until the DDW treatment, while no eggs were detected after day 0 in 36 of the 38 IVP-treated dogs. Findings from copro-PCR and antigen-ELISA were consistent with and confirmatory of the conclusions from worm counts and FECs. Conclusions A single, orally administered dose of this chewable tablet formulation is effective in treating canine infections with adult hookworms ( U. stenocephala , A. caninum ) and T. leonina . Non-terminal studies present a valid means of determining the efficacy of anthelmintic treatments for these canine intestinal parasites. Graphical Abstract