Background: Ascarid infections are among the most prevalent intestinal parasitic infections occurring in dogs around the world, with Toxocara canis and Toxascaris leonina commonly observed. Toxocara canis can cause considerable disease in dogs and humans, and year-round prophylactic treatment and control in dogs is recommended. Elimination of immature stages of these parasites before egg-laying will reduce environmental contamination and the risk of infection for both dogs and humans. Studies were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio ™) against induced immature adult (L 5) and adult T. canis, and adult T. leonina infections in dogs. Methods: Six negative-controlled, masked, randomized laboratory studies were conducted. Two studies each evaluated efficacy against immature adult (L 5) T. canis, adult T. canis, and adult T. leonina. Sixteen to 40 dogs were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio ™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy was based on the number of worms recovered at necropsy 7-10 days after treatment compared to placebo control. Results: Based on geometric mean worm counts, efficacy of the sarolaner + moxidectin + pyrantel combination was ≥ 95.2% against immature adult T. canis, ≥ 97.3% against adult T. canis, and ≥ 89.7% against adult T. leonina. There were no treatment-related adverse events in any study. Conclusions: These studies confirm the efficacy of a single dose of a new oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio ™) against immature adult and adult T. canis, and adult T. leonina infections in dogs.

Background: Five studies were conducted to evaluate a novel oral combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio ™), for efficacy against induced flea infestations, speed of kill and effects on flea reproduction on dogs. Methods: Based on pre-treatment flea counts, dogs were randomly allocated to treatment with a single, oral dose of either placebo or Simparica Trio ™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/ kg pyrantel (as pamoate salt) on Day 0. All dogs were infested with approximately 100 unfed, adult fleas (C. felis or C. canis) prior to treatment and weekly for 5 weeks post-treatment. In Studies 1, 2 and 3, the number of viable fleas were comb-counted at 24 h after treatment and after each weekly infestation; Study 2 also included groups treated with tablets containing sarolaner-alone (1.2 mg/kg), moxidectin-alone (24 µg/kg) or pyrantel-alone (5 mg/kg). In Study 4, flea counts were conducted at 3, 4, 8 and 12 h after treatment and subsequent weekly infestations to establish speed of kill. In Study 5 (flea reproduction), dogs were housed in an enclosure designed to facilitate collection of flea eggs. Results: Efficacy of Simparica Trio ™ against C. felis was ≥ 99.7% and against C. canis was 100% at 24 h after treatment and after subsequent infestations for at least 35 days. Treatment with sarolaner-alone had similar efficacy to Simparica Trio ™ , while moxidectin-alone and pyrantel-alone were no different from placebo at most time points. In Study 4, significant flea killing started at 4 h after treatment; by 8 h after treatment, all treated dogs were free of fleas. Following weekly re-infestation, the combination product reduced fleas by ≥ 97.8% within 12 h for 28 days. Simparica Trio ™ reduced flea egg-laying by 100% for 35 days. No treatment-related adverse reactions occurred in any study. Conclusions: A single dose of Simparica Trio ™ at the recommended minimum dose provided highly efficacious and rapid treatment within 4 h of existing flea infestations and persistent control of fleas on dogs for 5 weeks. The efficacy against fleas resulted in 100% prevention of flea reproduction for over a month following a single oral dose.

Background: Infection with Angiostrongylus vasorum may cause severe clinical disease, even death in dogs, however, due to the often non-specific clinical signs, diagnosis is not always straightforward. Regular prophylactic treatment may offer a safe means to protect dogs against infection. The efficacy of a novel oral endectocide containing moxidectin, sarolaner and pyrantel was investigated for the prevention of angiostrongylosis in dogs in three placebocontrolled, randomized, masked studies. The initial study (Study 1) determined the efficacious dosage of moxidectin in the combination product by evaluating three different dose levels, and two follow-up studies (Studies 2 and 3) confirmed the efficacy of the selected moxidectin dose. Methods: Animals were infected orally with 200 infective third-stage larvae (L3) of A. vasorum and were treated 28 days later with the combination product or with placebo. Timing of dosing relative to infection allowed for efficacy to be evaluated against the immature adult (L5) stage. Dogs in Study 1 received treatments with oral tablets to deliver 3, 12 or 24 µg/kg moxidectin in combination with 2 mg/kg sarolaner and 5.0 mg/kg pyrantel (as pamoate salt) or placebo. In Studies 2 and 3, Simparica Trio ™ tablets were administered to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy of the combination product was calculated as the percent reduction in adult worm counts at necropsy relative to placebo. Results: In Study 1, the 3, 12 and 24 µg/kg moxidectin dosage in the combination product provided 7.2%, 54.5% and 94.7% efficacy against the immature adult stages of A. vasorum, respectively. Studies 2 and 3 confirmed that the efficacy of 24 µg/kg moxidectin combined with 1.2 mg/kg sarolaner and 5 mg/kg pyrantel in Simparica Trio ™ was ≥ 92.9%. All three studies established that a single oral administration of 24 µg/kg moxidectin in the combination product provided effective prophylactic treatment for angiostrongylosis, reduced L1 production and fecal excretion and minimized the tissue damage to the lungs. Conclusions: A single oral treatment of dogs with Simparica Trio ™ providing moxidectin at a minimum dose of 24 µg/kg was efficacious in the prevention of angiostrongylosis.

Background: Ancylostomatids ('hookworms') are among the most important zoonotic nematode parasites infecting dogs worldwide. Ancylostoma caninum and Uncinaria stenocephala are two of the most common hookworm species that infect dogs. Both immature and adult stages of hookworms are voracious blood feeders and can cause death in young dogs before infection can be detected by routine fecal examination. Hence, treatment of both immature and adult stages of hookworms will decrease the risk of important clinical disease in the dog as well as the environmental contamination caused by egg-laying adults, which should reduce the risk of infection for both dogs and humans. The studies presented here were conducted to evaluate the efficacy of a novel, oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio ™), against induced larval (L 4), immature adult (L 5) and adult A. caninum, and adult U. stenocephala infections in dogs. Methods: Eight negative-controlled, masked, randomized laboratory studies were conducted. Two separate studies were conducted against each of the target parasites and stages. Sixteen or 18 purpose bred dogs, 8 or 9 in each of the two treatment groups, were included in each study. Dogs experimentally infected with the target parasite were dosed once on Day 0 with either placebo tablets or Simparica Trio ™ tablets to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Timing of dosing relative to parasite inoculation allowed for efficacy to be evaluated primarily against the target parasite stage. Worm counts were conducted 7 or 8 days after treatments during necropsy. Efficacy was based on the number of worms recovered at necropsy compared to placebo control. Results: Based on geometric mean worm counts, efficacy of Simparica Trio ™ was ≥ 98.4% against L 4 larval stage of A. caninum, ≥ 99.8% against immature adult (L 5) A. caninum, and 100% against adult A. caninum and adult U. stenocephala. Conclusions: These studies confirm the efficacy of a single oral dose of a novel, chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio ™) against L 4 larval and immature adult (L 5) A. caninum, and adult A. caninum and U. stenocephala infections in dogs.

Background: Tick infestations can cause direct deleterious effects to dogs as a result of tick blood-feeding, and indirectly ticks can transmit disease agents that can be detrimental to the health of both dogs and humans. Six laboratory studies were conducted to support dosage selection and efficacy confirmation of a novel combination of sarolaner, moxidectin and pyrantel against four tick species that commonly infest dogs in Europe. Methods: Two studies were conducted against Dermacentor reticulatus (one of which was a dose determination study), two against Ixodes ricinus, and one each against Ixodes hexagonus and Rhipicephalus sanguineus (sensu lato). In each study, eight purpose-bred Beagle or mix-breed dogs were randomly allocated to each treatment group and infested with 50 unfed adult ticks on Days-2, 5, 12, 19, 26 and 33. On Day 0 dogs were treated orally with placebo or the combination product. In the dose determination study, dogs received sarolaner at point dosages of 0.6 mg/ kg, 1.2 mg/kg or 2.4 mg/kg in combination with moxidectin and pyrantel, and in all other studies dogs received Simparica Trio ™ to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt). Efficacy was assessed based on live tick counts conducted 48 hours after treatment and each weekly infestation. Results: There were no treatment-related adverse events in any study. In the dose determination study, 1.2 mg/ kg sarolaner was the lowest dosage evaluated that provided > 90% efficacy for at least 28 days and therefore was selected as the dosage to provide tick control for at least one month following a single oral treatment. In the dose confirmation studies, a single oral dose of Simparica Trio ™ provided ≥ 99.2% efficacy against existing infestations of all tick species, and against re-infestations efficacy was ≥ 97.2% against D. reticulatus for 28 days and against all other species for 35 days. Conclusions: These studies support the sarolaner dose selected and confirm the efficacy of a single oral dose of Simparica Trio ™ against existing infestations and re-infestations of the common tick species infesting dogs in Europe for at least one month.