Evaluation of an 11.2% spinetoram topical spot-on solution for the control of experimental and natural flea (Ctenocephalides felis) infestations on cats in Europe.

Spinetoram is the newest member the spinosyn-class of natural products to be commercialized for flea control on cats in the United States under the tradename Cheristin® for cats. This report describes results from two laboratory studies and a multi-center clinical field trial designed to confirm the efficacy of a topical spot-on solution containing spinetoram (11.2% w/w, 130 mg/mL) against European strains of the cat flea, Ctenocephalides felis. In the laboratory studies, cats were allocated to one of two treatment groups of eight animals each: negative control (mineral oil) or spinetoram, both applied as a topical spot-on at the base of the skull on Day 0. Cats were infested with ∼100 newly emerged, unfed adult fleas on Days -2 or -1, 7, 14, 21, 28 and 35. To calculate efficacy, fleas were counted and removed 48 h after treatment, and 48 h after each subsequent infestation through week 5. Spinetoram treatments provided 100% efficacy through at least day 16 and ≥ 97% efficacy (arithmetic mean) for one month. For the field trial, 23 clinics from Northern and Southern Europe participated in the study that compared the effectiveness and safety of spinetoram and fipronil/(S)-methoprene treatments over a period of two months. There were 258 and 248 evaluable efficacy cases for month 1 and month 2, respectively, with 300 total evaluable cases for safety. Treatments were administered on Day 0 and again on Day 30 (±3 days). The effectiveness of treatments was calculated based on reduction in live flea counts on Days 14, 30, 44 and 60 (±3 days) relative to flea counts obtained on Day 0. Efficacy (geometric mean percent flea reduction) on Days 14, 30, 44 and 60 was 97.0%, 95.0%, 99.3% and 99.1% for spinetoram, respectively, and 86.1%, 80.9%, 92.4% and 92.3% for fipronil/(S)-methoprene, respectively. Spinetoram was deemed non-inferior at all intervals and superior to fipronil/(S)-methoprene at Days 30 and 60. Clinical signs of flea allergy dermatitis (FAD) were markedly improved following spinetoram treatment, as demonstrated through statistically significant reductions in severity of FAD scores for most of the clinical signs when compared to fipronil/(S)-methoprene treatment. There was a lower overall adverse event incidence rate for spinetoram (5.1%) versus fipronil/(S)-methoprene treatment (11.5%).

Assessment of the combination of spinosad and milbemycin oxime in preventing the development of canine Angiostrongylus vasorum infections.

Angiostrongylus vasorum is an increasingly reported parasite in Europe that develops in dogs after ingestion of infective third stage larvae (L3) that reside in gastropod molluscs which are needed to complete the parasite's life-cycle. Infection can produce a diversity of clinical signs, determined by involvement of the respiratory, neurological, and/or coagulation system, with a likely fatal outcome in the absence of treatment. Few drugs have been shown to reliably prevent infection, and data on treatment of infections is limited. A controlled, randomized, partially blinded laboratory study was therefore executed to evaluate the efficacy and safety of a combination tablet of spinosad/milbemycin oxime in dogs inoculated with approximately 250 A. vasorum L3. Sixteen healthy nematode free adult dogs were randomly allocated to two study groups of 8 dogs each. Thirty days post inoculation (dpi) all dogs in the fed state were treated: dogs in group B were treated with spinosad and milbemycin oxime at the dose rates of 45-60 mg/kg and 0.75-1.0mg/kg bodyweight, respectively, approximately the lower half portion of the expected full unit dose range; dogs in group A were treated with placebo tablets. All dogs were euthanized and necropsied 56-58 dpi. The heart and lungs were examined to determine the presence of A. vasorum. All placebo group dogs were infected at necropsy with counts ranging from 22 to 98 adult worms and a geometric mean worm count of 55.2. In contrast, the geometric mean worm count in the spinosad/milbemycin oxime group was 0.7 with worm numbers ranging from 0 to 8. The results of this study demonstrate that a single treatment with the tablet combination of spinosad and milbemycin oxime administered 30 dpi provided 98.8% preventive efficacy against development of adult A. vasorum infections. Monthly treatments with spinosad and milbemycin oxime have the potential to prevent the establishment of infections with A. vasorum in dogs.

Safety and efficacy of spinosad chewable tablets for treatment of flea infestations of cats.

OBJECTIVE: To compare safety and efficacy of spinosad and selamectin and determine effects of those products on flea allergy dermatitis (FAD) in cats. DESIGN: Randomized clinical trial. Animals-211 client-owned cats. PROCEDURES: Cats with ≥ 5 fleas evaluated at 8 veterinary clinics were allocated to receive spinosad (50 to 100 mg/kg [22.7 to 45.5 mg/lb], PO; n = 139) or selamectin (≥ 6 mg/kg [≥ 2.7 mg/lb], topically; 72) once per month. Flea comb counts and FAD scores were determined on day -1, between days 27 and 33, and between days 85 and 95 (evaluations 1, 2, and 3, respectively); day 0 was the first day of drug administration. RESULTS: The most common adverse event was vomiting (14.3% and 2.4% of spinosad- and selamectin-treated cats, respectively). Evaluation 2 and 3 geometric mean flea counts for spinosad-treated cats were significantly lower than those for selamectin-treated cats. Percentage reductions in flea counts for the spinosad and selamectin groups were 97.5% and 88.8% (evaluation 2) and 99.3% and 97.7% (evaluation 3), respectively. At evaluations 2 and 3, 70.6% and 92.6% of spinosad-treated cats and 29.4% and 64.7% of selamectin-treated cats were free of fleas, respectively. Weighted FAD scores for spinosad- and selamectin-treated cats decreased 94.2% and 80.0% during the study, respectively. Spinosad tablets were successfully administered during 98.1% of treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study indicated spinosad and selamectin both reduced flea counts and FAD scores for cats, although spinosad was more effective. Monthly oral administration of spinosad may be practical for treatment of flea infestations and FAD in cats.

Speed of kill efficacy and efficacy of flavored spinosad tablets administered orally to cats in a simulated home environment for the treatment and prevention of cat flea (Ctenocephalides felis) infestations.

The efficacy of spinosad against adult fleas (Ctenocephalides felis) on cats was evaluated in two separate controlled, blinded studies-one to determine flea knockdown and speed of flea kill (SOFK) on experimentally infested cats, another to assess the ability of spinosad to prevent flea infestations in a simulated home environment (SHE) study design. In each study, pre-treatment live flea counts were used as a blocking factor to randomize cats to treatment, and treated in the fed state, with flavored tablets containing either no active ingredient (control) or spinosad (50-100mg/kg in the SOFK study; 50-75 mg/kg body weight in the SHE study). In the SOFK study, 6 cats per group were infested with unfed adult fleas on Day -1. Groups 1-5 received control tablets; groups 6-10 received spinosad tablets. Flea counts were conducted at 0.5, 2, 4, 8 and 24h post-dosing. In the SHE study, 12 flea-free cats per group, treated on Days 0, 30 and 60, were maintained in solid-sided cages with solid carpeted floors. Each cat was infested on Days 1, 7 and 14 with 100 unfed adult fleas. Individual flea comb counts were performed on Days 3, 9, 16, 21, 28, 35, 42, 49, 56, 63, 70, 77, 84, 91 and 95. After each count, except Day 95, up to 300 live fleas were replaced on each cat. To augment flea challenge, the carpeted area in each cage was sprinkled weekly with larval flea growth media (dried blood, yeast). In the SOFK study, reductions in mean flea counts in the spinosad groups were observed at all post-treatment assessments, beginning at 0.5h post-infestation with significant differences (p<0.0001) from vehicle-treated cats from 2h post-treatment when efficacy was >90%, through the final flea counts 24h post-infestation when no fleas were found on spinosad treated cats. In the SHE study, GM post-treatment flea counts in the control group ranged between 38.9 and 107.0 (arithmetic means 58.8-118.1); no live fleas were combed from spinosad-treated cats (100% effectiveness) at any time point post-treatment. No adverse events that were attributable to the treatments were observed in either study. These studies demonstrated that spinosad administered orally to cats is safe and effective, providing >90% efficacy from 2h post-dosing and 100% knockdown at 24h, and preventing infestations over a 95 day study period from a flea-contaminated simulated home environment.