Fleas and ticks can be found globally and are of both veterinary and human health concern due to their ability to transmit various vector-borne diseases. Heavy flea and tick infestations can result in significant blood loss, while flea infestations can result in intense pruritus. The use of safe and effective ectoparasiticides in veterinary medicine is a crucial part of protecting both pets and humans from infestations and transmission of vector-borne diseases. The efficacy of a novel endectocide, Credelio Quattro, containing lotilaner, moxidectin, praziquantel, and pyrantel, was evaluated in four masked studies: one against Ctenocephalides felis and three against the dose-limiting tick Rhipicephalus sanguineus. Dogs were orally administered placebo, Credelio Quattro™, lotilaner only (Credelio™, Study 2), or pyrantel only (Study 2) in a fed state on Day 0. Experimental infestations with C. felis were conducted on Days −1, 6, 13, 20, 29, and 35 with 100 adult fleas. Fleas were removed and categorized as either live or dead 24 h post-treatment and 24 h post-infestation thereafter. Experimental infestations with R. sanguineus were conducted on Days −2, 5, 12, 19, and 30 with 50 adult ticks. Ticks were removed and categorized as attached or unattached and then live or dead 48 h post-treatment and 48 h post-infestation thereafter. Credelio Quattro demonstrated 100

Abstract Background The efficacy of a novel oral combination product, Simparica Trio™, containing sarolaner, moxidectin and pyrantel was evaluated against five tick species that commonly infest dogs in the USA, Amblyomma americanum, Amblyomma maculatum, Dermacentor variabilis, Ixodes scapularis and Rhipicephalus sanguineus. Methods Laboratory studies were conducted against two different strains of each tick species. In each study, 10 purpose-bred Beagle or mixed-breed dogs were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 (45–55) unfed adult ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs received either a single oral dose of 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) or placebo. Tick counts were conducted at 48 h post-treatment and after each subsequent weekly re-infestation for A. maculatum, D. variabilis, I. scapularis and R. sanguineus studies and at 48 hours or at 72 h post-treatment and after weekly re-infestation in the first and second A. americanum studies, respectively. Results No treatment-related adverse reactions occurred in any study. In all studies, placebo-treated dogs maintained infestations throughout the entire study duration, and dogs treated with Simparica Trio™ had significantly lower (P ≤ 0.0010) mean live tick counts than placebo-treated dogs at all time-points. Against A. maculatum, D. variabilis, I. scapularis and R. sanguineus, a single oral dose of Simparica Trio™ evaluated at 48 h post-treatment provided ≥ 98.9% efficacy against existing infestations, and within 48 h of re-infestation efficacy was ≥ 90.4% through at least Day 28 (except for R. sanguineus on Day 14 in a single study with an efficacy of 89.7%). Against A. americanum, Simparica Trio™ provided ≥ 99.4% efficacy at ≤ 72 h after treatment of existing infestations and maintained ≥ 98.4% efficacy at ≤ 72 h after re-infestation through at least Day 35. Conclusions A single dose of Simparica Trio™ administered orally at the minimum label dosage of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel provided treatment and control of the common tick species infesting dogs in the USA for at least one month.

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.

Background Recent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis . The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains. Methods Dogs were inoculated 30 days prior to first treatment with 50 third-stage (L 3 ) larvae of a ML-resistant strain of D. immitis , ZoeLA or JYD-34. In each study, dogs (six per group) were randomized to treatment with six monthly doses of placebo, four or six monthly doses of 24 µg/kg moxidectin, or six monthly doses of Heartgard® Plus or Interceptor® Plus at their label dose rates. Efficacy was evaluated by adult heartworm counts approximately nine months after L 3 inoculation. Results All negative-control dogs were infected with adult heartworms (geometric mean, 35.6; range, 24–41) for ZoeLA and (geometric mean, 32.9; range, 30–37) for JYD-34. Efficacies against ZoeLA for moxidectin, Heartgard® Plus and Interceptor® Plus were ≥ 96.1%, 18.7% and 21.2%, respectively. Adult counts for both moxidectin-treated groups were significantly lower than negative control ( P < 0.0001), significantly lower than Heartgard® Plus and Interceptor® Plus ( P < 0.0001), but not significantly different from each other ( P = 0.5876). Counts for Heartgard® Plus and Interceptor® Plus were not significantly different than negative control ( P ≥ 0.2471). Efficacies against JYD-34 were ≥ 95.9%, 63.9% and 54.6% for moxidectin, Heartgard® Plus and Interceptor® Plus, respectively. Counts for all groups were significantly lower than negative control ( P ≤ 0.0001). Counts for six monthly doses of moxidectin were significantly lower than those for four monthly doses ( P = 0.0470), and the counts for both moxidectin-treated groups were significantly lower than Heartgard® Plus and Interceptor® Plus ( P ≤ 0.0002). Conclusions Moxidectin administered orally at 24 µg/kg to dogs for four or six consecutive months was ≥ 95.9% effective in preventing the development of two ML-resistant heartworm strains and resulted in significantly fewer adult D. immitis than in dogs treated with Heartgard® Plus or Interceptor® Plus when administered for six consecutive months at their approved label dosages in two laboratory efficacy studies.

Abstract Background The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs in the USA and is the vector of important zoonotic pathogens, including Borrelia burgdorferi, the causative agent of Lyme disease. Rapid onset of activity is important in reducing the feeding activity of ticks, thereby reducing the possibility of transmission of infections. The speed of kill of a novel oral combination product, Simparica Trio™ containing sarolaner, moxidectin and pyrantel was evaluated in a well-controlled laboratory study against an existing infestation and subsequent weekly induced infestations of I. scapularis ticks on dogs. Methods Dogs were allocated randomly based on host suitability tick counts to treatment with a single 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). All dogs were infested with approximately 50 unfed adult I. scapularis ticks at a 1:1 sex ratio on Days −2, 7, 14, 21, 28 and 35. Tick counts were conducted at 8, 12 and 24 h after treatment on Day 0 and after each subsequent infestation. Results No treatment-related adverse events occurred during the study. Dogs in the placebo-treated group maintained adequate tick infestations for the duration of the study. Day 0 tick counts at 8 h after treatment with Simparica Trio™ were reduced relative to placebo against an existing infestation with efficacy of 67.5%, demonstrating that Simparica Trio™ started killing ticks soon after treatment. Efficacy was 98.4 % at 12 h and 99.4% at 24 h. Rapid speed of kill was maintained throughout the month, with efficacy of ≥ 94.2% at 24 h after re-infestation through Day 28. Conclusions A single dose of Simparica Trio™ administered orally to dogs at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) was safe and began to kill existing I. scapularis ticks within 8 h after treatment and resulted in ≥ 94.2% efficacy within 24 h against re-infestations for a month.

The efficacy of a single topical application of a combination product containing selamectin and sarolaner (selamectin/sarolaner; Revolution® Plus/Stronghold® Plus) was evaluated in seven laboratory studies against Ixodes scapularis (three studies), Dermacentor variabilis (two studies), or Amblyomma maculatum (two studies). In each study, cats were randomly allocated to treatment groups based on pre-treatment host-suitability tick counts. On Days -2, 5, 12, 19, 26 and 33, the cats were infested with unfed adult ticks. On Day 0, cats were treated with either a placebo (vehicle control) or with the spot-on solution at the minimum dose of 6.0 mg selamectin and 1.0 mg sarolaner/kg bodyweight. In one study with I. scapularis and one with D. variabilis an additional group of cats was treated with selamectin alone (Revolution®, Zoetis) at 6.0 mg/kg bodyweight. Tick counts were conducted after treatment and after each weekly re-infestation and efficacy determined relative to placebo-treated animals. There were no treatment-related adverse reactions in any of the studies. Geometric mean live tick counts were significantly (P < 0.05) lower in the selamectin/sarolaner-treated groups compared to the geometric mean tick counts in the placebo-treated groups at all time-points in all studies. For all species, a single topical administration of the selamectin/sarolaner combination resulted in>90% efficacy against existing infestations based on geometric means. Efficacy against weekly re-infestations was >90% based on geometric means for at least 5 weeks for I. scapularis and D. variabilis, and for at least 4 weeks against A. maculatum. Selamectin alone had no efficacy against I. scapularis, where counts on selamectin-treated cats were not significantly different from placebo at all time points (P > 0.05), and for D. variabilis, counts were not significantly different from placebo at 2, 3 and 5 weeks after treatment (P > 0.05) and efficacy was never greater than 85%. Thus, the activity of the sarolaner against three common tick species found on cats in the US is complementary to the existing broad-spectrum parasite control of selamectin. The inclusion of sarolaner with selamectin in a combination product (Revolution® Plus/Stronghold® Plus) provides for the treatment of existing tick infestations and gives at least one month of control against re-infestation following a single topical application.

Two studies were performed to determine the 24-hour efficacy of FRONTLINE (R) Plus (fipronil/(S)-methoprene) against the Tampa 2014 isolate of Ctenocephalides felis fleas. This isolate of fleas was collected during a field study where there was a perceived lack of efficacy of FRONTLINE Plus for Dogs against Ctenocephalides felis fleas. Two well-controlled laboratory studies were performed spatially and temporally separate, in two different facilities, against this isolate. In the first study, eight cats were treated with FRONTLINE Plus for Cats on Day 0, and eight cats remained as mineral oil-treated controls. Cats were infested with 100 fleas of the Tampa 2014 isolate on Days 1, 7, 14, 21, and 28, and the fleas were removed and counted 24 hours later. In the second study at a separate facility, 8 dogs were treated with the appropriate dose of FRONTLINE Plus for Dogs for their weight on Day 0, and 8 dogs remained as mineral oil-treated controls. Dogs were then infested with 100 fleas of the isolate on Days 1, 7, 14, 21, and 28, and the fleas were removed and counted 24 hours later. For Study 1, cats treated with FRONTLINE Plus had significantly (p<0.01) fewer live fleas than the controls 24 hours post-infestation on each assessment day. Efficacy for FRONTLINE Plus for Cats was 90.3%, 99.6%, 98.8%, 93.3%, and 85.6% on Days 2, 8, 15, 22, and 29, respectively. For Study 2, dogs treated with FRONTLINE Plus also had significantly (p<0.01) fewer live fleas than the controls 24 hours post-infestation on each assessment day. Efficacy for FRONTLINE Plus for Dogs was 99.6%, 100%, 100%, 100%, and 97.6% on Days 2, 8, 15, 22, and 29, respectively. FRONTLINE Plus for Cats and FRONTLINE Plus for Dogs demonstrated high efficacy against the Tampa 2014 isolate of Ctenocephalides felis fleas throughout the two 29-day studies. It was later discovered that, in the original field study, the owners of the homes in which the perceived inactivity against fleas had taken place had been bathing their dogs in oil-cutting shampoos and/or dish detergent during the study. This is one of many potential confounders that can affect the performance of a topical flea control product. The results of the present studies demonstrate that the true effectiveness of FRONTLINE Plus against Ctenocephalides felis fleas was consistent with previous well-controlled studies over the last 20 years. These results indicate that, when there appears to be lack of effectiveness with a flea control product, one should always consider and explore all possibilities.

Two separate studies were performed to evaluate the 24-hour efficacy of FRONTLINE (R) Plus for Dogs (fipronil/(S)-methoprene, Boehringer Ingelheim, Duluth, GA, USA) and FRONTLINE Gold for Dogs (fipronil/(S)-methoprene/pyriproxyfen, Boehringer Ingelheim, Duluth, GA, USA) against Ixodes scapularis ticks on Days 2, 9, 16, 23, and 30. From a pool of 28 dogs, 24 dogs with the highest tick counts were allocated to one of three treatment groups: Group A comprised eight control dogs treated with 0.5 mL of mineral oil each, Group B comprised eight dogs treated with FRONTLINE Plus (0.67 mL for dogs 5 to 22 lbs, or 1.34 mL for dogs 23 to 44 lbs), and Group C comprised eight FRONTLINE Gold-treated dogs (0.67 mL for dogs 5 to 22 lbs, or 1.34 mL for dogs 23 to 44 lbs). The first study compared Groups A and B, and the second study compared Groups A and C. Both studies utilized the same control dogs. Both studies were performed at the same time, on the same days, at the same facility. Combining the two studies, 24 dogs were treated with mineral oil (Group A), FRONTLINE Plus (Group B), or FRONTLINE Gold (Group C) on Day 0. All dogs were infested with 50 live, unfed Ixodes scapularis ticks on Days 1, 8, 15, 22, and 29 post-treatment, and all ticks were removed and counted 24 hours later on Days 2, 9, 16, 23, and 30. Dogs treated with FRONTLINE Plus had significantly (p<0.01) fewer live ticks than the controls at 24 hours post-infestation on Days 2, 9, 16, 23, and 30. Geometric mean efficacy was 100% at Days 9 and 23; >99% at Days 2 and 16; and 93.2% at Day 30. Dogs treated with FRONTLINE Gold had significantly (p<0.01) fewer live ticks than the controls at 24 hours post-infestation on Days 2, 9, 16, 23, and 30. Geometric mean efficacy was 100% at Days 9, 16, and 23; >99% at Day 2; and 98.4% at Day 30. Both products demonstrated excellent efficacy and persistent activity against Ixodes scapularis tick infestations at 24 hours for a full 30 days.

A study was performed to compare the 12-hour efficacy of FRONTLINE (R) Gold (fipronil/(S)-methoprene/pyriproxyfen) with that of SIMPARICA (R) (sarolaner) against Ixodes scapularis tick infestations on dogs. Based on pre-treatment tick count, 24 dogs were allocated to one of three groups, eight dogs in each group. On Day 0, each dog in Group B was treated with a dose of commercially available FRONTLINE Gold for Dogs appropriate for its weight, and each dog in Group C was treated with a dose of commercially available SIMPARICA appropriate for its weight. Group A dogs remained untreated throughout the duration of the study. On each of Days 1, 7, 14, 21, and 28, all dogs were infested with 50 live, unfed Ixodes scapularis ticks, and at 12 hours post-infestation on Days 2, 8, 15, 22, and 29, ticks were removed from all dogs and counted. Using arithmetic means for all calculations, dogs treated with FRONTLINE Gold had significantly (p<0.01) fewer live ticks than the controls at 12 hours post-infestation on all evaluation days from Day 2 to Day 29. FRONTLINE Gold 12-hour arithmetic mean efficacy was 99.1%, 100%, 100%, 100%, and 94.7% on the same days. Dogs treated with SIMPARICA had significantly (p<0.01) fewer live ticks than the controls at 12 hours post-infestation on the same days. SIMPARICA 12-hour arithmetic mean efficacy was 97.0%, 96.1%, 92.6%, 87.3%, and 84.5% on the same days, respectively. Dogs treated with FRONTLINE Gold had significantly (p<0.05) fewer live ticks than dogs treated with SIMPARICA on Day 15.

The speed of kill of a novel, topical product containing selamectin in combination with sarolaner (selamectin/sarolaner; Revolution (R) Plus/Stronghold (R) Plus) was evaluated against Ixodes scapularis ticks on cats. Sixteen cats were randomly allocated to a treatment group and treated topically on Day 0 with either placebo (vehicle control) or 6 mg/kg selamectin plus 1 mg/kg sarolaner. Cats were infested with approximately 50 unfed viable adult I. scapularis ticks on Days -2, 7, 14, 21, 28 and 35. Efficacy was assessed at 4, 8, 12, 24, 48 and 72 h after treatment on Day 0 and at 4, 8, 12 and 24 h after post-treatment re-infestations. There were no adverse reactions to the topical treatment with selamectin/sarolaner. Placebo-treated cats maintained tick infestations throughout the study. Treatment with selamectin/sarolaner significantly reduced tick counts within 12 h (P < 0.0001) and resulted in 100% efficacy by 24 h. For subsequent re-infestations, live tick counts were significantly reduced by 12 h after infestation on Day 7 (P = 0.0120) and by 24 h for Days 14-35 (P < 0.0001). At 24 h after the post-treatment re-infestations, efficacy based on geometric (arithmetic) means was >= 96.1% (94.5%) through Day 21, 75.3% (67.7%) on Day 28 and 66.4% (56.4%) on Day 35. Thus, a single topical dose of Revolution (R) Plus/Stronghold (R) Plus at the recommended minimum dose started killing ticks within 12-24 hours after treatment and re-infestations for up to 5 weeks. High acaricidal efficacy (>= 90% reduction in tick burden) was achieved within 24 h after treatment and subsequent re-infestations for at least three weeks.

A study was performed to compare the 6-hour efficacy of FRONTLINE (R) Gold (fipronil/(S)-methoprene/pyriproxyfen) with that of SIMPARICA (R) (sarolaner) against Ctenocephalides felis flea infestations on dogs. Twenty-four dogs were allocated to one of three groups, eight dogs in each group. On Day 0, each dog in Group B was treated with a dose of commercially available FRONTLINE Gold for dogs appropriate for its weight, and each dog in Group C was treated with a dose of commercially available SIMPARICA appropriate for its weight. Group A dogs remained untreated throughout the duration of the study. On each of Days 1, 7, 14, 21, and 28, all dogs were infested with 100 live, unfed Ctenocephalides felis fleas, and 6 hours later, all fleas were removed and counted. Using arithmetic means for all calculations, dogs treated with FRONTLINE Gold had significantly (p<0.01) fewer live fleas than the controls at 6 hours post-infestation on all assessment days from Day 1 to Day 28. FRONTLINE Gold's 6-hour efficacies were 88.8%, 98.2%, 99.2%, 95.2%, and 83.0% on Days 1, 7, 14, 21, and 28, respectively. Dogs treated with SIMPARICA had significantly (p<0.01) fewer live fleas than the controls at 6 hours post-infestation on the same days. SIMPARICA 6-hour efficacies were 100%, 100%, 98.8%, 86.6%, and 87.0% on the same days, respectively. There was no significant (p>0.05) difference in flea count between the dogs treated with FRONTLINE Gold and those treated with SIMPARICA on any of the 6-hour post-infestation assessments.

A new spot-on formulation of selamectin plus sarolaner was evaluated against fleas for adulticidal efficacy, and for the effect on egg production and hatching when applied to flea-infested cats. Ten male and ten female adult domestic shorthair cats were randomly assigned to one of two treatment groups based on pre-treatment flea counts. Cats received topical treatment on Day 0 in a single spot to the dorsal scapular area with either a placebo formulation or with the combination formulation at the minimal dose of 6.0mg selamectin plus 1.0mg sarolaner per kg bodyweight. On Days -1, 5, 12, 19, 26 and 33, cats were infested with approximately 100 (±5) unfed Ctenocephalides felis fleas. At 24h after treatment or 48h after subsequent flea infestation, cats were housed for a 20-h period in a cage to allow collection of flea eggs. At the end of this period, flea eggs were collected from the cages and cats were combed to remove and count live fleas. Emerged viable larvae and emerged adult fleas were counted 3days and 35days, respectively, after egg collection. The new spot-on formulation of selamectin plus sarolaner provided 100% efficacy against adult fleas up to Day 36 following a single application. Fleas on placebo-treated cats produced large numbers of eggs throughout the study, with individual counts ranging from 110 to 1256 eggs. Following treatment, four flea eggs were collected from a single selamectin/sarolaner-treated cat on Day 29, but there were no eggs collected from any other selamectin/sarolaner-treated animal during the study. No larvae or adult fleas developed from these four eggs. From the eggs collected from the placebo-treated cats, the mean percentage of live larvae and adults that emerged ranged from 67.3% to 84.2% and from 50.7% to 81.8%, respectively. A single topical treatment with a new spot-on formulation of selamectin plus sarolaner at the minimum label dose thus controlled fleas on cats and was 100% effective in preventing flea reproduction for over one month after treatment.

Three studies were performed to assess the efficacy, speed of kill, and residual effects of FRONTLINE (R) Gold for Dogs (fipronil/(S)-methoprene/pyriproxyfen, Boehringer Ingelheim, Merial, Inc., Duluth, GA) against Ctenocephalides felis fleas. Although temporally separate, all three studies were performed at the same facility, each using eight dogs per treatment group, with two treatment groups in the first two studies and three treatment groups in the third study. In the first study, 16 dogs were infested with 100 unfed adult fleas on Day 2 following treatment, and the fleas were removed and counted 30 minutes later. In the second study, the same dogs were infested with 100 unfed adult fleas on Days 2, 9, 16, 23, and 30 following treatment, and the fleas were removed and counted 12 hours later. In the third study, a group of eight FRONTLINE Plus-treated dogs were included, so 24 total dogs were infested with 100 unfed adult fleas, and the fleas were removed and counted 6 hours later on Days 2, 9, 16, 23, and 30. In the first study, dogs treated with FRONTLINE Gold had significantly (p=0.01) fewer live fleas than the control dogs 30 minutes post-infestation on Day 2. Geometric mean efficacy was 64.8%. In the second study, dogs treated with FRONTLINE Gold had significantly (p<0.01) fewer live fleas than the control dogs 12 hours post-infestation on Days 2, 9, 16, 23, and 30. Geometric mean efficacy was 100% on Days 2, 9, 16, and 23, and 99.1% on Day 30. In the third study, dogs treated with FRONTLINE Plus had significantly (p<0.01) fewer live fleas than the control dogs at 6 hours post-infestation on all assessments through Day 23, and significantly (p<0.05) fewer live fleas than the control dogs at six hours post-infestation on Day 30. FRONTLINE Plus Geometric mean efficacy was 99.3%, 100%, 99.0%, 97.4%, and 74.4% on Days 2, 9, 16, 23, and 30, respectively. Dogs treated with FRONTLINE Gold had significantly (p<0.01) fewer live fleas than the control dogs at six hours post-infestation on all assessments through Day 30. Geometric mean efficacy was 100%, 100%, 99.5%, 99.9%, and 98.4% on Days 2, 9, 16, 23, and 30, respectively. In this study, dogs treated with FRONTLINE Gold had significantly (p<0.01) fewer live fleas than those treated with FRONTLINE Plus on Days 23 and 30. A single dose of FRONTLINE Gold for Dogs (1.34 ml) demonstrated excellent efficacy, speed of kill, and residual effects against Ctenocephalides felis fleas for a full 30 days, and demonstrated better persistent speed of kill and residual effects than FRONTLINE Plus at the six-hour count for a full 30 days.

The rapid speed of kill of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was demonstrated against three tick species known to infest dogs in Europe or the United States. Efficacy was measured against an existing infestation and against subsequent weekly re-infestations for 35 days after treatment. Dogs were randomly allocated to treatment with a single oral dose of either placebo or sarolaner (2mg/kg) based on pre-treatment host-suitability tick counts. Dogs were infested with approximately 50 unfed adult Ixodes scapularis, Ixodes ricinus or Amblyomma maculatum ticks on Days-2, 7, 14, 21, 28 and 35. Tick counts were conducted at 4 (I. scapularis only), 8, 12 and 24h after treatment on Day 0 and after each subsequent re-infestation. No treatment-related adverse reactions occurred during any of these studies. Dogs in the placebo-treated groups maintained adequate tick infestations (recovery of 20-70% of applied ticks) throughout the duration of the studies. Following treatment, live tick counts were significantly reduced relative to placebo at the 8h post treatment counts indicating that sarolaner started killing existing infestations of ticks rapidly after treatment. Efficacy was 90.1% against I. ricinus, 98.8% against I. scapularis, and 99.2% against A. maculatum within 12h, and 100% efficacy was achieved at 24h after treatment against all three tick species. This speed of kill was maintained throughout the month with ≥95.7%, ≥98.7% and ≥89.6% efficacy against I. scapularis, I. ricinus, and A. maculatum, respectively, at 24h after re-infestation at least through Day 28.

Fleas are a ubiquitous ectoparasite infesting dogs and cause direct discomfort, allergic reactions and are responsible for the transmission of several pathogens. The rapid speed of kill of a parasiticide is important to alleviate the direct deleterious effects of fleas, reduce the impact of allergic responses, and break the flea life cycle. In this study, the speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner (Simparica™) against fleas on dogs was evaluated and compared with spinosad in combination with milbemycin oxime (Trifexis®) for 5 weeks after a single oral dose.

The efficacy of a single oral dose of a novel isoxazoline, sarolaner (Simparica™, Zoetis), for the treatment and control of flea infestations on dogs was confirmed in five laboratory studies. The studies were conducted using adult purpose-bred Beagles and/or mixed breed dogs. All animals were individually identified and housed, and were allocated randomly to treatment with either placebo or sarolaner (eight to 10 per group) based on pretreatment parasite counts. Three studies used cat flea (Ctenocephalides felis felis) strains recently isolated from the field from the US, EU, or Australia; in the fourth study a laboratory strain (KS1) with documented tolerance to a number of insecticides such as fipronil, imidacloprid, and permethrin was used. In the fifth study, dogs were infested with dog fleas, Ctenocephalides canis. Dogs were treated orally on Day 0 with a placebo or a sarolaner tablet providing a minimum dose of 2mg/kg. Dogs were infested with approximately 100 unfed, adult fleas prior to treatment and at weekly intervals post-treatment. Comb counts were conducted to determine the numbers of viable fleas at 24h after treatment and after each subsequent infestation. Efficacy against C. felis and C. canis was 99.8-100% from treatment through Day 35. In all five studies, elimination of existing infestations was achieved within 24h after dosing, with only a single live C. felis found on one dog on Day 1. Similarly, control of flea challenges was achieved within 24h after infestation throughout the 35day study periods, with only single live C. felis found on two dogs on Day 28 in one study, and on a single dog on Day 35 in another study. There were no adverse reactions to treatment with sarolaner. These studies confirmed that a single oral dose of sarolaner at 2mg/kg provided highly effective treatment of existing C. felis infestations and persistent control of C. felis on dogs for 35days after treatment. Efficacy equivalent to that seen with C. felis was confirmed against C. canis and a known insecticide-tolerant strain of C. felis.

BackgroundAcceptability and palatability of oral formulations are critical issues in establishing and maintaining optimal owner compliance, especially for essential, regularly administered treatments such as monthly flea/tick control products. Such dosage forms are generally developed to be highly palatable if possible, to best ensure they are voluntarily and completely consumed by the pet. The present study aimed to compare the preference of dogs between two commercially available oral ectoparasiticide formulations of afoxolaner (NexGard (R), Merial) and sarolaner (Simparica (TM), Zoetis).Methods: In two separate experiments, 204 individual dogs from two independent facilities (100 dogs at site 1 and 104 dogs at site 2), were simultaneously offered a choice of similarly-sized, commercially available afoxolaner and sarolaner chewable tablets. The 204 dogs were given an opportunity to smell both products, then both products were simultaneously offered to each dog by hand, allowing the dog to choose and consume one, or the other product, each day for 4 consecutive days. The products were offered from alternate hands on each day, to negate any handedness effect. Individual consumption and related behaviors were recorded. Each dog in the respective studies received offerings from the same individual (Investigator) throughout the studies. The total number of chewable tablets consumed of each formulation was recorded, and the product preference of each dog was defined as the consumption of a given formulation on more days.Results: A total of 622 (81.4%) afoxolaner chews and 142 (18.6%) sarolaner chews was consumed in both studies. The consumption ratio significantly (p<0.0001) favored NexGard to Simparica at 4.4 to 1. Additionally, significantly (p<0.0001) more dogs consumed the NexGard Chewables than the Simparica Chewables on each day.In these two studies combined, for dogs showing a preference over the test period, 93.1 % (p<0.0001) of them preferred NexGard to Simparica, where "preference" is defined as consuming the entire product on more days. The preference ratio of NexGard Chewables over Simparica Chewables was 13.5 to 1.Conclusion: This study demonstrated that when dogs were offered a choice between the two ectoparasiticide products, a significant preference was observed for the NexGard formulation.

Background: The black-legged (or deer) tick, Ixodes scapularis, commonly infests dogs and cats in North America and is the main vector for the pathogen that causes Lyme disease in dogs and humans.The speed of kill of a parasiticide is critical to minimize the direct and deleterious effects of tick infestation and especially to reduce the risk of tick-borne pathogen transmission.In this study, speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica ™ ), against I. scapularis on dogs was evaluated and compared with afoxolaner (NexGard ® ) for five weeks after a single oral dose.Methods: Twenty four dogs were randomly allocated to treatment with either placebo, sarolaner (2 to 4 mg/kg), or afoxolaner (2.5 to 6.8 mg/kg) based on pretreatment tick counts.Dogs were examined and live ticks counted at 8, 12, and 24 h after treatment and subsequent re-infestations on Days 7, 14, 21, 28 and 35.Efficacy was determined at each time point relative to counts for placebo dogs.Results: A single oral dose of sarolaner provided >99 % efficacy within 24 h of treatment and >95 % against subsequent weekly re-infestations of ticks consistently to Day 35.For the earlier time points, sarolaner significantly reduced tick counts versus placebo from Day 0 to Day 21 at 8 and 12 h, and on Day 35 at 12 h (P ≤ 0.0174), while afoxolaner was only significantly lower at 8 h on Days 0 and 14 (P ≤ 0.0309), and at 12 h on Day 0 only (P < 0.0001).Significantly more live ticks were recovered from afoxolaner-treated dogs than from sarolaner-treated dogs at 24 h after infestation from Day 14 to Day 35 (P ≤ 0.0278).At 24 h, efficacy (based on geometric mean counts) of afoxolaner declined to less than 80 % from Day 21 through the end of the study, while efficacy for sarolaner was >95 % for 35 days.There were no adverse reactions to treatments. Conclusions:In this controlled laboratory evaluation, sarolaner had a faster speed of kill against I. scapularis than afoxolaner.This was noticeably more pronounced towards the end of the monthly treatment period.The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and re-infestation over 35 days suggests this treatment will provide highly effective and reliable control of ticks over the entire treatment interval, and should reduce the risk of tick-borne diseases, including Lyme disease whose agent is vectored by I. scapularis.

The efficacy of fluralaner spot-on solution administered once topically against induced infestations with Rhipicephalus sanguineus was evaluated in dogs over a 12-week post-treatment period.