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.

中文翻译：

---

实验室研究评估了含有 sarolaner、莫昔克丁和噻嘧啶 (Simparica Trio™) 的新型口服组合产品治疗和控制狗跳蚤感染的功效。


背景 进行了五项研究来评估一种含有沙罗那、莫昔克丁和噻嘧啶的新型口服组合片剂 (Simparica Trio™)，其对抗诱导跳蚤感染的功效、杀死速度以及对狗跳蚤繁殖的影响。方法 根据治疗前的跳蚤计数，狗被随机分配接受单次口服安慰剂或 Simparica Trio™ 治疗，最低标签剂量为 1.2 mg/kg sarolaner、24 µg/kg 莫昔克汀和 5 mg/kg在第 0 天给予噻嘧啶（作为双羟萘酸盐）。在治疗前和治疗后 5 周内，每周用大约 100 只未喂食的成年跳蚤（猫跳蚤或犬跳蚤）感染所有狗。在研究 1、2 和 3 中，在处理后 24 小时和每周感染后对活跳蚤数量进行梳状计数；研究2还包括用含有单独的sarolaner (1.2 mg/kg)、单独的莫昔克丁(24 µg/kg)或单独的噻嘧啶(5 mg/kg)的片剂治疗的组。在研究 4 中，在治疗后 3、4、8 和 12 小时以及随后的每周感染后进行跳蚤计数，以确定杀死速度。在研究 5（跳蚤繁殖）中，狗被安置在一个旨在促进跳蚤卵收集的围栏中。结果 在治疗后 24 小时以及随后感染至少 35 天后，Simparica Trio™ 对猫念珠菌的功效≥ 99.7%，对犬念珠菌的功效为 100%。单独使用 Sarolaner 的治疗与 Simparica Trio™ 具有相似的疗效，而单独使用莫西菌素和单独使用噻嘧啶在大多数时间点与安慰剂没有差异。在研究 4 中，处理后 4 小时开始显着杀死跳蚤；治疗后 8 小时，所有接受治疗的狗身上都没有跳蚤了。每周重新感染后，该组合产品在 28 天内 12 小时内将跳蚤减少了 ≥ 97.8%。 Simparica Trio™ 在 35 天内将跳蚤产卵量减少 100%。任何研究中均未发生与治疗相关的不良反应。结论 单剂量的 Simparica Trio™（推荐最小剂量）可在现有跳蚤感染的 4 小时内提供高效、快速的治疗，并持续控制狗身上的跳蚤长达 5 周。单次口服剂量后，对跳蚤的功效可在一个多月内 100% 阻止跳蚤繁殖。