The studies were conducted in accordance with the World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestation on dogs and cats [23] and complied with Good Clinical Practices [24]. The protocols were reviewed and approved by the Animal Care and Ethics Committee of the Director-General of NSW Department of Primary Industries.
Two field studies were conducted, one in northeastern (northern study) and one in southeastern (southern study) Australia. Northeastern Australia (Queensland) has a subtropical climate compared to the temperate climate in southeastern Australia (New South Wales and Victoria). The number and location of enrolled veterinary clinics in the different regions are summarised in Fig. 1 and Table 1.
Fig. 1Clinic locations of dogs enrolled in two clinical field studies in the northern and southern regions of Australia
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Table 1 Clinic location and number of dogs enrolled in two clinical field studies in the northern and southern regions of AustraliaFull size table
Client-owned dogs recruited from veterinary clinics were used in the studies. Dogs were from diverse households and lived both indoors and outdoors. Dogs came from both single dog households and households with multiple dogs (maximum of 3 dogs) and/or cats. There were no breed or sex restrictions, but dogs intended for breeding or that were pregnant or lactating were not eligible for enrolment. For inclusion in the study, at least one dog in the household had to harbor at least 5 live fleas at screening. All dogs were at least 8 weeks of age and ≥ 1.3 kg in body weight at enrolment. Dogs aged less than 14 weeks or with a body weight of ≤ 2.3 kg and allocated to the spinosad treatment group were excluded from the study to comply with Comfortis® label recommendations. Dogs in the study were not allowed to have been treated with any ectoparasiticide with persistent activity within 30 days or with a short-acting ectoparasiticide within 14 days of the first treatment.
The northern and southern studies were analysed and reported separately. Within each region, the study was a multi-centric, blinded, positively-controlled trial with a randomized block design. Households were allocated randomly to treatment with sarolaner or spinosad in a ratio of 2:1 based on the order of enrollment. Within each household, one dog was randomly nominated as the primary dog and up to 2 additional dogs were enrolled as supplementary dogs. All enrolled dogs from the same household received the same treatment as the primary dog. Only the primary dogs were included in the efficacy evaluation whereas all dogs were included in the safety evaluation.
All dogs were confirmed to be in good general health prior to enrollment based on the physical examination performed by a veterinarian. Dogs were housed and maintained under their normal home conditions for the duration of the study.
Because sarolaner has efficacy against Australian tick species (I. holocyclus and Rhipicephalus sanguineus) for up to 35 days, sarolaner-treated dogs were not allowed to receive any other product for tick control. For the spinosad-treated dogs, amitraz collar (Preventic®, Virbac Australia) was allowed as an optional tick control if indicated. The clients were requested to remove any tick collars on all dogs prior to each veterinary clinic visit in order to maintain the blinding of treatment groups. All cats in the households were treated with commercially available flea products.
No additional products (systemic, premise, and/or over-the-counter treatments including insecticidal shampoos or collars) that had activity against fleas were permitted to be used on any animal in the household for the duration of the study. Any concomitant medications used during the study were recorded along with any abnormal health events.
Day 0 was set as the day the primary dog in each household received the first treatment. Dogs received three consecutive monthly treatments on study days 0, 30 and 60. For the follow-up treatments on Days 30 and 60, the visits were allowed to deviate by ± 3 days of the target date. All treatments were dispensed according to a randomization plan that was provided for each clinic before study start. Treatment dispensing was based upon the most recent body weight. Treatments were administered by an unmasked study participant (the dispenser) at the clinics in presence of the owners. Animals enrolled in the sarolaner group were treated with the appropriate strength sarolaner chewable tablet (Simparica®, Zoetis) to provide the recommended minimum dosage of 2 mg/kg (range 2–4 mg/kg). There were no restrictions regarding the prandial state at the time of sarolaner administration, therefore tablets could be administered with or without food. Dogs enrolled in the positive control group received spinosad (Comfortis® Chewable Tablets, Elanco), according to the manufacturer’s label recommendations to deliver ≥ 30 mg/kg spinosad. Spinosad was administered with a small meal in order to comply with the approved dosing directions for that product.
Flea counts on primary dogs were conducted prior to treatment on Day 0, and on post-treatment Days 14, 30, 60 and 90 (the post-treatment evaluations could be conducted ± 3 days of the target day) by a veterinarian.
Flea counts were conducted by personnel trained to a standardized methodology. The dog was combed with a fine toothed flea comb that was uniquely identified for each dog. The combing proceeded in a systematic manner to ensure all areas of the dog were combed. Each dog was examined for at least 10 minutes. If any fleas were found in the last 5 minutes, the examination was continued in 5 minute increments until no fleas were encountered. All fleas were removed from the dog and discarded after counting. Fleas maintaining an upright orientationor moving in a coordinated manner were considered to be live. Only live flea counts were recorded.
Data were summarised and analysed for each of the two studies separately, using SAS version 9.3 (SAS Institute Inc., Cary, NC, USA). The individual animal (primary dog) was the experimental unit for the efficacy analysis and all treatment comparisons were carried out at the 5% significance level (two-sided).
Data were excluded from the efficacy analysis following protocol deviations such as incorrect dosing or where dosing or flea counts were not conducted within ± 3 days of the target day (after Day 0).
Percent efficacy (percentage reduction in live flea counts from pre-treatment count on Day 0) was calculated for each animal at each time point after Day 0. Percent efficacy was analyzed using a general linear mixed model for repeated measures with fixed effects for treatment, time and the treatment by time interaction. The random effects included clinic, the interaction between clinic and treatment, block within clinic, animal within block, treatment and clinic, the interaction of clinic, treatment and time, and residual. Least squares means were used as estimates of the treatment means at each time point.
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