Safety and efficacy of a novel oral chewable combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against natural flea infestations in client-owned dogs in the USA.

BACKGROUND: One randomized, controlled clinical field study was conducted in 18 general veterinary practices throughout the USA to evaluate the safety and efficacy of a novel oral chewable combination tablet, Simparica Trio™, containing sarolaner, moxidectin and pyrantel for the treatment and prevention of fleas on dogs. METHODS: Client-owned dogs, from households of three or fewer dogs were eligible for enrollment. Four hundred and twenty-two dogs from 251 households were enrolled. Households were randomly assigned in a 2:1 ratio to treatment with either 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) or afoxolaner (NexGard®, Boehringer-Ingelheim) at the label dose. One dog per household was selected as the primary dog for efficacy evaluations. Treatments were dispensed and dogs were dosed in their home environment on Day 0 and on approximately Day 30. Flea counts and examination for clinical signs of flea allergy dermatitis (FAD) were performed at the initial visit the day before or on Day 0 prior to treatment and on Days 30 and 60. Additionally, all dogs were examined for general health at each visit and blood and urine were collected for clinical pathology at screening and Day 60. RESULTS: Simparica Trio™ reduced geometric mean live flea counts by 99.0% by Day 30 and by 99.7% by Day 60. As a result of the rapid reduction in flea infestations, clinical signs associated with FAD substantially improved following treatment. Simparica Trio™ was well-tolerated and a diverse range of concomitant medications were administered to dogs during the course of the study. Simparica Trio™ chewable tablets were well-accepted by dogs, with the majority of flavored chewable tablets (91.9%) voluntarily consumed by free choice without, or when offered in food. CONCLUSIONS: Simparica Trio™ administered orally once monthly for two consecutive treatments was safe and effective against natural flea infestations and substantially improved clinical signs associated with FAD in client-owned dogs in a field study conducted in the USA.

Laboratory and field studies to investigate the efficacy of a novel, orally administered combination product containing moxidectin, sarolaner and pyrantel for the prevention of heartworm disease (Dirofilaria immitis) in dogs.

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.