Csilla Becskei

Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex spp. and Otodectes cynotis.

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.

Efficacy of a novel oral formulation of sarolaner (Simparica™) against four common tick species infesting dogs in Europe.

The efficacy of single oral treatment of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against four tick species known to commonly infest dogs in Europe. Eight laboratory studies were conducted using adult purpose-bred Beagle dogs. In each study, 16 animals were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with 50 unfed adult Dermacentor reticulatus (two studies), Ixodes hexagonus (three studies), Ixodes ricinus (two studies) or Rhipicephalus sanguineus (one study) ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated orally with placebo or sarolaner tablets providing the minimum dose of 2.0mg/kg bodyweight and tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions in any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly (P≤0.0001) lower in the sarolaner-treated group compared to the tick counts in the placebo group at all time-points. A single oral administration of sarolaner resulted in 100% efficacy against existing infestations of all tick species except R. sanguineus, for which the efficacy was 99.7%, within 48h. Efficacy against weekly re-infestations was ≥97.5% for all tick species for 35 days. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2 mg/kg, resulted in ≥99.7% efficacy within 48h against existing tick infestations, and in ≥97.5% efficacy against weekly re-infestations, for at least 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in Europe.

Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica™), for the treatment of sarcoptic mange in dogs

The efficacy of the novel isoxazoline, sarolaner (Simparica™) was investigated in dogs with clinical signs consistent with sarcoptic mange and harbouring natural infestations of Sarcoptes scabiei. One placebo-controlled laboratory study and one multi-centred field study with a commercial comparator containing imidacloprid/moxidectin (Advocate(®) spot-on) were conducted. Oral or topical treatments were administered on Days 0 and 30. Up to 10 skin scrapings were taken for the assessment of S. scabiei infestations from each dog before treatment and on Days 14, 30, 44 and 60 in the laboratory study, and on Days 30 and 60 in the field study. In the laboratory study, efficacy was calculated based on the percent reduction of mean live mite counts compared to the placebo group. In the field study parasitological cure rate (% dogs free of mites) was determined and non-inferiority of sarolaner to the control product was assessed. In the laboratory study 44 mixed breed dogs were enrolled in four batches. Due to decreasing mite counts in the placebo treated dogs, immunosuppression with dexamethasone (0.4mg/kg three times per week for two weeks) was initiated in all dogs on study at that time (n=6) and those subsequently enrolled (n=14). In the field study, dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 79 dogs were assessed for efficacy and safety, and an additional 45 dogs were assessed for safety only. There were no treatment related adverse events in either study. In the laboratory study, no mites were found on any sarolaner-treated dogs 14 days after the first treatment except for one dog that had a single mite on Day 44. In the field study, the parasitological cure rate was 88.7% and 100% in the sarolaner group and 84.6% and 96.0% in the imidacloprid/moxidectin group, on Days 30 and 60, respectively. Statistical analysis showed that sarolaner was non-inferior to imidacloprid/moxidectin at both time points. The clinical signs of sarcoptic mange, including hair loss, papules, pruritus, erythema, and scaling/crusting improved throughout the study. Sarolaner was safe, achieved 100% reduction in the numbers of S. scabiei detected and resulted in marked improvement of the clinical signs of sarcoptic mange in dogs following two monthly oral administrations.

Evaluation of the speed of kill, effects on reproduction, and effectiveness in a simulated infested-home environment of sarolaner (Simparica™) against fleas on dogs.

Four studies were conducted to evaluate the speed of kill, effect on egg production, and efficacy in a simulated infested-home environment of a novel isoxazoline, sarolaner (Simparica™, Zoetis), against fleas on dogs. Individually identified and housed, purpose-bred Beagles were used in each study and were allocated randomly to groups based on pretreatment parasite counts. In two speed of kill studies, groups of dogs infested with 100 fleas prior to treatment were treated orally with placebo or sarolaner tablets providing the minimum dose of 2mg/kg and then re-infested with fleas weekly for five weeks post-treatment. Comb counts were conducted to determine the numbers of viable fleas at one to three, four, eight and 12h after treatment and each subsequent infestation. In the egg production study, sarolaner- and placebo-treated dogs were similarly challenged with fleas and at 48h after each infestation the dogs were housed for 20h in cages allowing the collection and counting of all flea eggs produced during this period. Collected eggs were incubated to evaluate hatch and development to adults. The last study used dogs housed in a flea-infested simulated-home environment. Dogs were allocated to treatment with either placebo or sarolaner tablets providing a dose of 2mg/kg once a month for three treatments. Flea infestations were assessed by comb counts (fleas were replaced on the dogs) on Days 14, 30, 44, 60, 74 and 90. The speed of kill studies demonstrated that a single 2mg/kg oral dose of sarolaner started killing fleas within three to four hours after treatment or subsequent re-infestations for up to a month, and achieved ≥98% control of fleas by eight hours after treatment or re-infestation for 28 days. In the study to assess effects on flea reproduction, a single oral treatment of sarolaner resulted in the complete cessation of egg-laying for 35 days. This rapid kill of fleas and inhibition of reproduction were confirmed in a simulated-home environment where the existing infestations were reduced by >95% within two weeks of the first treatment and eliminated from the dogs after two monthly doses.

Efficacy and safety of a new spot-on formulation of selamectin plus sarolaner in the treatment of naturally occurring flea and tick infestations in cats presented as veterinary patients in Europe

Two randomised, blinded, multi-centre field studies were conducted in Europe (Germany, Italy, France, Hungary) to demonstrate the efficacy and safety of three monthly applications of a new spot-on formulation of selamectin plus sarolaner (Stronghold® Plus, Zoetis) against natural flea or tick infestations in cats presented as veterinary patients. The spot-on formulation was administered at the commercial dose range of 6.0-12.0mg selamectin and 1.0-2.0mg sarolaner per kg bodyweight. In the flea study, the improvement in clinical signs associated with flea allergy dermatitis (FAD) was also monitored. Imidacloprid plus moxidectin (Advocate® for Cats, Bayer) and fipronil (Frontline® Spot on, Merial) were used as positive control products in the flea and tick studies, respectively. Treatments were administered on Days 0, 30 and 60. Efficacy was calculated based on the mean percent reduction of live parasite counts on post-treatment days 14, 30, 60 and 90 versus the pre-treatment count on Day 0. Non-inferiority of selamectin/sarolaner to the control products was assessed at each time-point using a non-inferiority margin of 15% at the one-sided 0.025 significance level. Cats were enrolled in a 2:1 ratio (selamectin/sarolaner:comparator). In the flea study, 277 cats were assessed for efficacy and safety, and an additional 170 cats were assessed for safety only. On days 14, 30, 60 and 90, efficacy against fleas was 97.4%, 97.3%, 98.8% and 99.4% in the selamectin/sarolaner-treated group and was 90.0%, 83.6%, 87.7% and 96.3% in the imidacloprid/moxidectin-treated group, respectively. Selamectin/sarolaner was non-inferior to imidacloprid/moxidectin at all time-points. For the 16 cats identified as having FAD at enrolment, clinical signs related to FAD improved following treatment administration. In the tick study, 200 cats were assessed for efficacy and safety, and a further 70 cats were assessed for safety only. Four tick species were identified. Overall efficacy against ticks was 96.7%, 92.6%, 98.8% and 99.5% in the selamectin/sarolaner-treated group and was 90.2%, 74.6%, 83.0% and 93.4% in the fipronil-treated group on Days 14, 30, 60 and 90, respectively. Selamectin/sarolaner was non-inferior to fipronil at all time-points, and was superior on Days 30 and 60. There were no serious treatment-related adverse events in any study. Thus, the new spot-on formulation of selamectin plus sarolaner administered at monthly intervals was safe and highly effective against natural infestations of fleas and ticks on cats, and improved clinical signs of FAD.

Efficacy and safety of a novel oral isoxazoline, sarolaner (Simparica™) in the treatment of naturally occurring flea and tick infestations in dogs presented as veterinary patients in Europe

Two randomised, blinded, multi-centered field studies were conducted in Europe to demonstrate the efficacy and safety of three monthly oral doses of sarolaner (Simparica™, Zoetis) administered at a minimum dosage of 2.0mg/kg (range 2-4mg/kg) against natural flea or tick infestation of dogs presented as veterinary patients. In the flea study, the improvement in clinical signs associated with flea allergy dermatitis (FAD) was also investigated. The palatability of the sarolaner chewable tablet formulation was evaluated in both studies. Spinosad (Comfortis(®) Chewable Tablets, Elanco) and fipronil (Frontline(®) Spot on, Merial) were used as positive controls in the flea and tick study, respectively. Treatments were administered on Days 0, 30 and 60. Efficacy was calculated based on the mean percent reduction of live parasite counts on post-treatment days 14, 30, 60 and 90 versus the pre-treatment count on Day 0. Non-inferiority of sarolaner to the control products was assessed at each time-point using a margin of 15% at the one-sided 0.025 significance level. Dogs were enrolled in a 2:1 ratio (sarolaner:comparator); 285 flea- and 181 tick-infested dogs were assessed for efficacy and safety, and 137 and 48 dogs were assessed for safety only, in the flea and tick study, respectively. There were no treatment-related adverse events. Efficacy against fleas was 98.8%, 99.4%, >99.9% and >99.9% in the sarolaner-treated group and 98.9%, 93.7%, 96.8% and 95.1% in the spinosad-treated group on Days 14, 30, 60 and 90, respectively. Sarolaner was non-inferior to spinosad at all time-points and was superior on Day 30. For the 42 dogs identified as having FAD at enrolment, the clinical signs of FAD improved in all dogs and the incidence was markedly reduced by the end of the study. Efficacy against ticks was 97.4%, 97.6%, 99.8% and 100% in the sarolaner-treated group and 94.1%, 88.5%, 89.9% and 98.1% in the fipronil-treated group on Days 14, 30, 60 and 90, respectively. Sarolaner was non-inferior to fipronil at all time-points, and was superior on Days 30 and 60. Sarolaner tablets were voluntarily and fully consumed within one minute in 93% of the 1280 occasions offered. Sarolaner administered orally at monthly intervals at a minimum dosage of 2 mg/kg was safe and highly effective against natural infestations of fleas and ticks on dogs. In addition, clinical signs FAD improved in dogs treated with sarolaner, and the flavored, chewable tablets were highly palatable.

Efficacy of a new spot-on formulation of selamectin plus sarolaner against four common tick species infesting cats in Europe

A single application of a new spot-on formulation of selamectin plus sarolaner (Stronghold®Plus, Zoetis) was evaluated for efficacy against the most common tick species infesting cats in Europe. In each of the seven laboratory studies, 16 adult and purpose-bred cats were randomly allocated to one of two treatment groups based on pre-treatment tick counts. Weekly infestations with 50 unfed adult Ixodes ricinus (2 studies), Ixodes hexagonus (1 study), Dermacentor reticulatus (2 studies), or Rhipicephalus sanguineus (2 studies) were scheduled on Days -2, 5, 12, 19, 26 and 33. Cats were treated on Day 0 with the spot-on formulation at the minimum recommended label dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight or with a placebo. Ticks were counted 48h after treatment and after each re-infestation. No treatment-related adverse reactions were recorded in any of the studies. Geometric mean live tick counts were significantly (P≤0.0012) lower in the selamectin/sarolaner-treated group compared to the placebo-treated group at all time-points. Against I. ricinus and I. hexagonus, efficacy was ≥97.2% against existing infestations and ≥97.4% against weekly re-infestations for at least 5 weeks. Treatment was 100% effective against existing R. sanguineus infestations and was ≥95.8% for at least 4 weeks. Against D. reticulatus treatment resulted in ≥94.4% efficacy for at least 4 weeks. Thus, a single application of the new spot-on formulation of selamectin plus sarolaner at the minimum dose provides rapid treatment of existing infestations and is at least one month effective against re-infestation by all relevant European tick species in cats.

Efficacy and speed of kill of a new spot-on formulation of selamectin plus sarolaner against flea infestations in cats

The efficacy of a new spot-on formulation of selamectin plus sarolaner against induced flea infestations in cats was confirmed in three placebo-controlled, blinded studies. Purpose-bred adult cats (n=8/group) were blocked by pre-treatment flea counts and randomly allocated to treatment with either a placebo or with the spot-on formulation at the minimum dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight. Treatments were applied topically once on Day 0. All cats were infested with approximately 100 unfed, adult Ctenocephalides felis prior to treatment and at weekly intervals for 5 weeks. In Studies 1 and 2 comb counts were conducted to determine the numbers of viable fleas 24h after treatment and subsequent weekly infestations. In Study 3, flea counts were conducted at 6, 12, 24 and 48h after treatment and 3, 6, 12 and 24h after subsequent weekly infestations to evaluate the speed of kill against fleas. Cats in the placebo-treated groups maintained flea infestations throughout all studies. In Study 1, no live fleas were found on any of the treated cats, resulting in 100% efficacy for 5 weeks after a single treatment (P≤0.0001). In Study 2, selamectin/sarolaner reduced flea counts by 92.4% immediately after treatment and by 97.7%-100% after re-infestations for five weeks (P≤0.0001). In the speed of kill study, selamectin/sarolaner started killing fleas within 12h after treatment administration and within 6h following re-infestation for at least 28days. Efficacy was 98.1% by 24h after treatment and 100% within 24h after re-infestations for 5 weeks. A single topical administration of a new spot-on formulation of selamectin plus sarolaner at the minimum dose rapidly and consistently kills fleas on cats for at least 5 weeks.

Efficacy of a new spot-on formulation of selamectin plus sarolaner in the treatment of Otodectes cynotis in cats

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.

Speed of kill of a new spot-on formulation of selamectin plus sarolaner for cats against induced infestations with Ixodes ricinus

The speed of kill of a new spot-on formulation containing selamectin plus sarolaner (Stronghold®Plus, Zoetis) for cats was evaluated against Ixodes ricinus ticks in a placebo-controlled, blinded study. Sixteen (16) cats were blocked by pre-treatment tick counts and randomly allocated to the placebo-treated group or the selamectin/sarolaner-treated group. Cats either received a single topical treatment at the minimum dose of 6.0mg selamectin and 1.0mg sarolaner per kg bodyweight or a placebo formulation on Day 0. On Days -2, 7, 14, 21, 28 and 35, cats were infested with approximately 50 unfed, viable and adult I. ricinus ticks. Tick counts were performed in situ 8 and 12h after treatment or re-infestation. Ticks were removed from the cats and counted at the 24h tick count. Acaricidal efficacy at each time point was calculated based on the reduction of mean live tick counts in the selamectin/sarolaner-treated group versus the placebo-treated group. There were no treatment-related adverse reactions during the study. Placebo-treated cats maintained infestations with mean tick counts ranging from 10.3 to 21.9 throughout the study. The new spot-on formulation of selamectin plus sarolaner demonstrated 99.3% efficacy (P<0.0001) within 24h after treatment against pre-existing infestations. For subsequent re-infestations, efficacy was >97.9% for at least 3 weeks and was 89.0% after the re-infestation on Day 28. Mean live tick counts were significantly reduced by 12h after re-infestation for at least 28 days (P<0.0338). Thus, a single application of the new spot-on formulation of selamectin plus sarolaner at the minimum label dose started killing ticks within 24h after treatment and within 12h after re-infestations for 4 weeks. High acaricidal efficacy was achieved within 24h after treatment and this persisted following subsequent re-infestations for a month.