Laboratory studies evaluating the efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) for the treatment and control of flea infestations on dogs

Abstract

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.

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

“…The efficacy against fleas shown in this study is consistent with that demonstrated previously for sarolaner alone in a field study [18]. Additionally, reductions in the numbers of fleas seen in the post-treatment evaluations in these dogs in this study are consistent with the rapid onset of activity of Simparica Trio ™ as demonstrated in a laboratory flea speed of kill study [19], with 100% reduction of flea egg-laying also being demonstrated in a laboratory flea reproduction study [19]. The combination of these effects results in the suppression of the flea populations in the dogs' environments by killing newly emerged fleas on the dogs before they lay eggs and contribute to the environmental re-infestation [20].…”

“…The combination of these effects results in the suppression of the flea populations in the dogs' environments by killing newly emerged fleas on the dogs before they lay eggs and contribute to the environmental re-infestation [20]. This flea control is consistent with a high adulticidal activity and breaking of the flea life-cycle through the cessation of flea reproduction that was seen in laboratory studies [19].…”

Efficacy of a novel oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against natural flea and tick infestations on dogs presented as veterinary patients in Europe

“…This high level of flea control is consistent with the adulticidal activity and breaking of the flea life-cycle through the cessation of flea reproduction that was seen in Simparica Trio ™ laboratory efficacy studies [17]. Against induced infections with adult C. felis and C. canis, a single oral dose of Simparica Trio ™ reduced live flea counts by ≥ 99.9% within 24 hours of treatment and by 100% within 24 hours of weekly re-infestation for 35 days [17]. Blood-feeding for at least 24 hours is required for a female flea to commence egg laying, thus fleas killed within 24 hours are not able to contribute to environmental contamination by flea eggs [18,19].…”

“…These results are comparable to the efficacy reported previously for other orally administered pulicidal medications belonging to both the isoxazoline [13][14][15] and spinosyn class [16] in dogs. This high level of flea control is consistent with the adulticidal activity and breaking of the flea life-cycle through the cessation of flea reproduction that was seen in Simparica Trio ™ laboratory efficacy studies [17]. Against induced infections with adult C. felis and C. canis, a single oral dose of Simparica Trio ™ reduced live flea counts by ≥ 99.9% within 24 hours of treatment and by 100% within 24 hours of weekly re-infestation for 35 days [17].…”

Evaluation of the speed of kill of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of Ixodes scapularis on dogs

“…Sarolaner belongs to a potent new class of ectoparasiticides (isoxazolines) and has been shown to provide consistent efficacy against fleas and ticks in Simparica ® and Simparica Trio ™ for 1 month following a minimum single oral dose of sarolaner at 2.0 and 1.2 mg/kg respectively [18][19][20]. Sarolaner exerts activity against invertebrates by blocking GABA-gated chloride channels [21,22].…”