The efficacy of sarolaner (Simparica™, Zoetis) was evaluated against Demodex spp. in dogs with generalized demodicosis and against Otodectes cynotis (otodectic mange) in dogs with induced infestations. In the first study, 16 dogs with clinical signs of generalized demodicosis and positive for Demodex spp. mites were randomly assigned to treatment with either sarolaner (2mg/kg) orally on Days 0, 30 and 60, or topical imidacloprid (10mg/kg) plus moxidectin (2.5mg/kg) solution every 7 days from Day 0 to Day 81. For sarolaner-treated dogs, pretreatment mite counts were reduced by 97.1% at 14days and 99.8% by 29 days after the first dose, with no live mites detected thereafter. Weekly imidacloprid plus moxidectin resulted in 84.4 and 95.6% reduction at these two time points, respectively, with no mites detected from Day 74 on. All dogs in both groups showed marked improvement in the clinical signs of demodicosis. In the second study, 32 dogs with induced infestations of O. cynotis were randomly assigned (eight per group) to oral sarolaner (2mg/kg) as a single treatment on Day 0 or as a two dose regime (Days 0 and 30), or a placebo group for each of the dose regimes. Sarolaner administered at 2mg/kg as a single oral dose resulted in a 98.2% reduction at Day 30 and two doses of sarolaner, administered one month apart, resulted in a 99.5% reduction in ear mites at Day 60 compared to placebo controls. There were no treatment related adverse events in either study. In these studies, sarolaner at an oral dose of 2mg/kg was highly effective in reducing the live mite counts associated with a natural infestation of Demodex spp. and an induced infestation of O. cynotis. In addition, the Demodex-infested dogs showed a marked improvement in the clinical signs of generalized demodicosis.

Background Dirofilaria immitis is a filarial parasite of dogs that can cause serious or fatal cardiopulmonary disease. Three studies were conducted to evaluate the efficacy and safety of monthly treatment with moxidectin in a chewable tablet product in combination with sarolaner and pyrantel to prevent heartworm disease in dogs after experimental challenge and in a clinical field study in the USA. Methods In two laboratory studies, dogs (8 per group) that had been inoculated 30 days prior with 50 third-stage D. immitis larvae were randomized to treatment on Day 0 with placebo or combination product, at the minimum dose of 24 µg/kg moxidectin, 2 mg/kg sarolaner and 5 mg/kg pyrantel (as pamoate salt). Study 2 also included groups treated with tablets containing moxidectin-alone (24 µg/kg) or sarolaner-alone (2 mg/kg). Efficacy was evaluated ~ 5 months after inoculation by adult heartworm counts at necropsy. In the field study, 410 dogs ≥ 8 weeks-old from 23 USA veterinary clinics were treated for 11 months with either combination product at 24–48 µg/kg moxidectin, 2–4 mg/kg sarolaner and 5–10 mg/kg pyrantel (n = 272) or Heartgard® Plus (ivermectin/pyrantel) at the label recommended dose rate (n = 138). Efficacy was evaluated on Day 330 using antigen and microfilaria testing to assess adult heartworm infection. Results In the laboratory studies, there were no heartworms recovered from any dog treated with the combination product or moxidectin alone and all dogs treated with placebo or sarolaner-alone were infected with 20–44 adult heartworms. In the field study, all dogs treated with the combination product tested negative for heartworm infection on Day 330, whereas two dogs treated with Heartgard® Plus tested positive. The Heartgard® Plus-treated dogs that tested heartworm positive were from the lower Mississippi River Valley region, where heartworm resistance has been confirmed to occur. The combination product was well tolerated in all studies. Conclusions In laboratory studies, no heartworms were recovered from dogs treated with a single dose of the novel combination product containing moxidectin, sarolaner and pyrantel. Additionally, in the field study no dog tested positive for adult heartworm infection when dosed with the combination product monthly for 11 months, while two dogs treated with Heartgard® Plus tested positive.

The efficacy of a single oral treatment with sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against five tick species known to infest dogs in the United States. A total of 10 laboratory studies, two against each species, were conducted using adult purpose-bred mongrels or Beagle dogs. In each study, 16 dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 unfed adult Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis or Rhipicephalus sanguineus ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated with a placebo or a sarolaner tablet providing a minimum dose of 2 mg/kg. Tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions during any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly lower (P≤0.0001) in the sarolaner-treated group compared to the tick counts in the placebo group at all timepoints. Treatment with sarolaner resulted in ≥99.6% efficacy against existing infestations of all five tick species within 48h. The efficacy against weekly post-treatment re-infestations of all tick species was ≥96.9% for at least 35 days after treatment. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2mg/kg, resulted in excellent efficacy within 48h against existing tick infestations, and against weekly re-infestations for 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide rapid treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in the US.

Three laboratory studies were conducted to determine the appropriate dose of sarolaner, a novel isoxazoline, for the treatment and month-long control of infestations of fleas and ticks on dogs. In the first study, dogs were treated orally with sarolaner suspension formulations at 1.25, 2.5 or 5.0mg/kg, and infested with Dermacentor reticulatus, Rhipicephalus sanguineus ticks and with Ctenocephalides felis felis (cat flea) prior to treatment and then weekly for up to 8 weeks. Fleas and ticks were counted 48h after treatment and after each subsequent infestation at 24h for fleas and 48h for ticks. The lowest dose of sarolaner (1.25mg/kg) provided 100% efficacy against fleas from treatment through Day 35 and 98.4% at Day 56. This dose of sarolaner resulted in 99.7-100% control of both species of ticks through Day 28. In Study 2, dogs were dosed orally with placebo or sarolaner suspension formulations at 0.625, 1.25 or 2.5mg/kg and infested with Ixodes scapularis prior to treatment and weekly for 6 weeks, Amblyomma americanum (pretreatment and Day 26), Dermacentor variabilis (Day 33) and A. maculatum (Day 41). Ixodes scapularis was the most susceptible; the lowest dose (0.625mg/kg) providing>95% efficacy through Day 43. Efficacy against D. variabilis on Day 35 was>95% at 1.25 and 2.5mg/kg, whereas the 0.625mg/kg dose gave only 61.4% efficacy. Amblyomma spp. were the least susceptible ticks; efficacy of the 1.25mg/kg dose at Day 28 for A. americanum was markedly lower (88.5%) than achieved for D. reticulatus (100%) at Day 28 and also lower than for D. variabilis at Day 35 (96.2%). In Study 3, dogs were dosed orally with placebo or sarolaner in the proposed commercial tablet (Simparica™) at 1.0, 2.0 or 4.0mg/kg, and infested with A. maculatum, one of the ticks determined to be dose limiting, prior to treatment and then weekly for 5 weeks. All doses gave 100% control of the existing infestation. The two highest dosages resulted in >93% control of subsequent challenges for 5 weeks. There was no significant improvement in efficacy provided by the 4.0 mg/kg dose over the 2.0mg/kg dose (P>0.05) at any time point. The 2.0mg/kg dose was superior to the 1.0mg/kg on Day 14 (P=0.0086) and as efficacy for 1.0mg/kg declined below 90% at Day 28, a single 1mg/kg dose would not provide a full month of tick control. Thus, 2.0mg/kg was selected as the sarolaner dose rate to provide flea and tick control for at least one month following a single oral treatment.

The efficacy of a new spot-on formulation of selamectin/sarolaner was evaluated against induced Otodectes cynotis infestations in cats in two randomized, blinded studies. Fourteen and 16 cats were randomly assigned to treatment groups in Studies 1 and 2, respectively. On Day 0, animals were either treated with placebo or with the spot-on formulation at the minimal dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight. Treatments were administered topically at the base of the neck. Presence of live mites was evaluated 14days after treatment administration by otoscopic examination and total live mite counts (adults plus immature) were conducted on Day 30 by ear lavage. Efficacy was calculated based on the reduction of mean total live mite counts on Day 30 in the selamectin/sarolaner-treated group versus the placebo-treated group. There were no treatment-related adverse reactions during the studies, apart from one cat in each treatment group with alopecia at the administration site. In both studies combined, live mites were present on Day 14, in 14 out of 15 cats in the placebo-treated groups and in 2 out of 15 cats in the selamectin/sarolaner-treated groups. On Day 30, the arithmetic mean live mite counts were 576.9 and 875.8 in the placebo-treated groups and 5.8 and 4.7 in the selamectin/sarolaner-treated groups, in Studies 1 and 2, respectively. The live mite counts were significantly (P≤0.0021) lower in the selamectin/sarolaner-treated groups compared to the placebo-treated groups with efficacies of 99.2% and 99.3%, in Studies 1 and 2 respectively. A single administration of a new spot-on formulation of selamectin/sarolaner at the minimum dose was safe and highly efficacious in the treatment of ear mite infestations in cats.