NexGard Spectra Research Articles

Efficacy of a chewable tablet containing sarolaner, moxidectin, and pyrantel (Simparica Trio®) in the treatment of sarcoptic mange caused by Sarcoptes scabiei mite infestations in dogs

BackgroundInfestation with Sarcoptes scabiei in dogs is a debilitating disease if left untreated and is transmissible to humans. Two field studies were conducted to confirm the efficacy of orally administered sarolaner in combination with moxidectin and pyrantel (Simparica Trio®) in the treatment of sarcoptic mange in dogs.MethodsClient-owned dogs with S. scabiei infestation were enrolled and received 2 monthly treatments. In the first, small-scale study, 12 dogs each were allocated randomly to treatment with either placebo or Simparica Trio®. Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, 44, and 60. Efficacy was calculated based on the percent reduction in arithmetic mean live mite counts relative to placebo. In the second, large-scale study, 75 dogs were allocated randomly to treatment with Simparica Trio® and 37 to treatment with afoxolaner + milbemycin oxime (NexGard Spectra®). Skin scrapings to detect live mites and assessment of clinical signs of sarcoptic mange were conducted on Days 0, 14, 30, and 60. The parasitological cure rate (percentage of dogs without live mites) was determined and non-inferiority of Simparica Trio® to the control product was assessed.ResultsIn the small-scale study, 2 monthly doses of Simparica Trio® resulted in a significant reduction (P ≤ 0.0050) in live S. scabiei mite numbers and provided a 99.2% reduction relative to placebo by Day 60. Clinical signs of sarcoptic mange improved throughout the study in Simparica Trio®-treated dogs. In the large-scale study, the parasitological cure rate on Days 30 and 60 was 97.3% and 100% in the Simparica Trio® group and 91.9% and 100% in the afoxolaner + milbemycin oxime group, respectively. The parasitological cure rate for Simparica Trio® was non-inferior to afoxolaner + milbemycin oxime at both time points. Clinical signs of sarcoptic mange improved throughout the study in both groups.ConclusionsTwo-monthly doses of Simparica Trio® reduced S. scabiei mite counts by 99.2% relative to placebo in one study and eliminated S. scabiei mites in 100% of dogs in the second study, thus confirming that Simparica Trio® is highly effective in the treatment of sarcoptic mange in dogs caused by S. scabiei var. canis.Graphical abstract

Efficacy of Afoxolaner Alone or in Combination with Milbemycin Oxime against <i>Rhipicephalus sanguineus</i> Lato Sensu in Naturally Infested Dogs in Colombia

The brown dog tick (Rhipicephalus sanguineus lato sensu) is the tick that most affects dogs worldwide and is therefore the main blood pathogen vector in dogs. The efficacy of afoxolaner 2.7 to 7.1 mg/kg NexGard® (group A) and afoxolaner plus milbemycin oxime 2.5 to 5.4 mg/kg and 0.5 to 1.1 mg/kg respectively NexGard Spectra® (Group B) against R. sanguineus, was evaluated in naturally infected sheltered dogs under high challenging conditions in four different areas of Colombia (Antioquia, Córdoba, Santander, and Meta). Tick counts (alive, dead, attached, and unattached) were performed on treated dogs, the average was calculated for the different areas to evaluate the efficacy of each treatment at six different times post-treatment (24 h, 48 h, 7 d, 14 d, 21 d, 30 d). None of the dogs showed adverse events related to the treatments. The average tick number pre-treatment was 68 in group A and 78.3 for group B indicating a strong natural infection of the dogs and their environment. Efficacy after 24 h against R. sanguineus was always above 90% with ≥97.4% for NexGard® and ≥93.7% for NexGard Spectra®. Consistent results were observed along all the observation periods with final efficacies (day 30) of ≥99.8% and 98.3% for NexGard® and NexGard Spectra®, respectively. In conclusion, both NexGard® and Nexgard Spectra® provided a curative effect and sustained efficacy against Rhipicephalus sanguineus for at least 30 days in highly contaminated shelter environments.

Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio\xae Plus) against natural flea and tick infestations on dogs presented as veterinary patients in Europe

BackgroundA pivotal randomised, blinded, positive-controlled, multicentre, European field study was conducted to evaluate the effectiveness and safety of a novel combination tablet of lotilaner and milbemycin oxime (Credelio® Plus) administered orally to client-owned dogs naturally infested with fleas and/or ticks.MethodsIn this field study, households with flea- or tick-infested dog(s) were enrolled on Day 0 into the study to provide data for either the tick or flea infestation cohorts. Households were randomised in a 2:1 ratio to receive either the combination investigational product (IP, Credelio Plus® tablets) or the control product (CP: Nexgard Spectra® tablets). Dogs were administered IP (flea cohort n = 135; tick cohort: n = 147) or CP (flea cohort: n = 67; tick cohort: n = 74) once every 4 weeks for a total of three times at a dose rate of 20.0–41.5 mg/kg bodyweight lotilaner and 0.75–1.53 mg/kg bodyweight milbemycin oxime (IP) or as recommended (CP). Percentage reduction was calculated by comparing individual dog flea and tick counts at each assessed post-treatment time point to their respective baseline (pre-treatment) infestation. Resolution of the clinical signs of flea allergy dermatitis (FAD) was assessed in flea-allergic dogs on the days that flea counts were performed.ResultsFlea effectiveness of Credelio Plus® after 3 consecutive monthly treatments was 100% against Ctenocephalides felis, C. canis and Pulex irritans. Tick effectiveness of Credelio Plus® over the same time frame was 99.3% for Ixodes ricinus and 100% against Rhipicephalus sanguineus (s.l.). Flea effectiveness of the CP after three consecutive monthly treatments was 100% against C. felis, C. canis and P. irritans. Tick effectiveness of the CP over the same time frame was 99.8% for I. ricinus and 100% against R. sanguineus. Credelio Plus® was well tolerated based on the safety assessments in all treated dogs in this field study. Within both treatment groups there was a reduction in total FAD scores from baseline.ConclusionsThis pivotal European field study demonstrated the excellent effectiveness and safety of a combination of lotilaner and milbemycin oxime (Credelio Plus®) administered orally to dogs naturally infested with fleas and/or ticks.Graphical

Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio\xae Plus) against natural intestinal nematode infections in dogs presented as veterinary patients in Europe

BackgroundA randomised, blinded, positive controlled, multicentre, Good Clinical Practice-compliant, pivotal field study was conducted to evaluate the effectiveness and safety of a new combination of lotilaner + milbemycin oxime tablets (Credelio® Plus; Elanco Animal Health) administered orally to client-owned dogs naturally infected with intestinal nematodes.MethodsClient-owned dogs presenting to veterinary clinics from households in France, Hungary and Germany were screened for intestinal nematodes. Dogs with an initial positive faecal egg count that was subsequently confirmed with a follow-up faecal examination to demonstrate the presence of naturally occurring mixed or mono-infections with Toxocara canis, Toxascaris leonina, Trichuris vulpis or Ancylostoma caninum were enrolled on Day 0 into the study. Households were randomised in an approximately 2:1 ratio to receive either an investigational product (IP; Credelio Plus tablets) or control product (CP; Nexgard Spectra® tablets) as treatment. Dogs were administered the IP (n = 278) or CP (n = 117) once on Day 0 at a dose rate of 0.75–1.56 mg/kg bodyweight milbemycin oxime and 20.0–41.5 mg/kg bodyweight lotilaner (IP) or as recommended (CP). Effectiveness of the IP and CP treatments was based on the post-treatment reduction in geometric mean faecal egg counts on Day 8 (range Day 7–10) after treatment as compared to their pre-treatment nematode faecal egg counts.ResultsGeometric mean (GM) faecal egg counts for T. canis, A caninum and T. vulpis were reduced by ≥ 97.2% in the Credelio Plus group and by ≥ 95.3% in the afoxolaner + milbemycin oxime group. There were insufficient data to calculate a percentage reduction in GM faecal egg counts between Day 0 and Day 8 for T. leonina due to low prevalence. Credelio Plus was well tolerated in this field study. Of the 355 total doses administered, 82.3% were accepted free choice in the IP group compared to 80.8% in the CP group.ConclusionsThis study demonstrated effectiveness (≥ 97.2% reduction), safety and tablet acceptance of a combination of milbemycin oxime and lotilaner (Credelio Plus) administered orally to dogs with natural intestinal infections of T. canis, A. caninum and T. vulpis.Graphical

Efficacy of milbemycin oxime/afoxolaner chewable tablets (NEXGARD SPECTRA\xae) against Capillaria aerophila and Capillaria boehmi in naturally infected dogs

BackgroundCapillaria aerophila and Capillaria boehmi parasitize the respiratory system of wild and domestic carnivores. Capillaria aerophila inhabits the trachea and bronchi of dogs and cats, while C. boehmi affects the nasal cavities and sinuses of dogs. In dogs the infection may be subclinical or characterized by varying respiratory distress.MethodsThe present study evaluated the efficacy of an oral formulation containing milbemycin oxime and afoxolaner (NEXGARD SPECTRA®) in dogs naturally infected with C. aerophila and/or C. boehmi from three enzootic areas of Italy. Dogs were enrolled pending fecal examination and molecular confirmation of respiratory capillarioses. Dogs were allocated in two groups: Group 1 (G1, 25 dogs), treated with a negative control product with no anthelmintic activity (afoxolaner, NEXGARD®), and Group 2 (G2, 26 dogs), treated with NEXGARD SPECTRA®. At the day of treatment administration (Day 0), all dogs were clinically examined. Dogs were again subjected to clinical and fecal examinations at Days 28 (± 4) and 56 (± 2). The primary criterion for treatment efficacy was the reduction of fecal Capillaria egg counts in G2 compared with G1. The regression of/recovery from baseline clinical signs was considered as a further efficacy criterion.ResultsPercentage reduction of fecal Capillaria egg counts in the NEXGARD SPECTRA® group compared to the control group was > 97% on Day 28 and 100% on Day 56, respectively (p < 0.05 for both time points). Twelve of the 13 dogs in the NEXGARD SPECTRA® group with respiratory signs prior to treatment were free of clinical signs at the end of the study. Conversely, the six control group dogs with respiratory signs prior to treatment remained symptomatic.ConclusionsResults of the present study showed that NEXGARD SPECTRA® was safe and highly efficacious in the reduction of C. aerophila and C. boehmi eggs after one treatment with a complete reduction of the egg output after the second administration associated with a recovery from respiratory signs.Graphical

Efficacy of combination products containing sarolaner, moxidectin and pyrantel (Simparica Trio\u2122) or afoxolaner and milbemycin (NexGard Spectra\xae) against induced infestations of Ixodes holocyclus in dogs

BackgroundThe Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™) and afoxolaner + milbemycin (NexGard Spectra®) was evaluated against an artificial infestation of I. holocyclus.MethodsTwenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days − 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal® (control group), Simparica Trio™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means.ResultsAgainst an existing infestation, efficacy of both Simparica Trio™ and NexGard Spectra® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study.ConclusionsSingle doses of Simparica Trio™ and NexGard Spectra® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days.

Evaluation of the effect of afoxalaner with milbemycin 1 oxime in the treatment of rabbits naturally infected with Psoroptes cuniculi.

Rabbits (Oryctolagus cuniculi) are very popular as pets. However, problems of otitits caused by Psoroptes cuniculi are one of the main reasons to visit the veterinarian. Isoxazolines are an alternative treatment to treat this mite, and therefore, an evaluation of the effectiveness of oral afoxalaner with milbemycin oxime in rabbits infected with P. cuniculi was carried out. Nineteen rabbits, of New Zealand breed, with otitis due to an infection with P. cuniculi, were treated, whereas six rabbits were left untreated and formed the control group. The ear canals of each individual were examined, through the collection of otic exudate samples with cotton swabs. These were visualized under the microscope to identify the ectoparasite. Each animal was treated with a single oral dose of 2.50 mg / kg of afoxolaner, and 0.50 mg / kg of milbemycin oxime. Clinical signs and lesions associated with the infection, such as the presence of detritus, cerumen and / or scabs, and erythema, were evaluated. After receiving the treatment, all the lesions were classified as: mild, moderate and intense, with a visual analog scale. A week after providing medication, there was a decrease in the lesions of the group treated with Nexgard Spectra®, without further topical or systemic treatment. The decrease was gradual in the treated group and no recurrence was detected of P. cuniculi infection in both ears. Thus, the administration of a single oral dose of afoxolaner with milbemycin oxime was effective for the treatment of P. cuniculi infection in rabbits.

Efficacy of a Single Oral Administration of Afoxolaner Alone or in Combination with Milbemycin Oxime against &amp;lt;i&amp;gt;Ixodes hexagonus&amp;lt;/i&amp;gt; Ticks in Dogs

The efficacy of afoxolaner (NexGard® and NexGard Spectra®, Boehringer-Ingelheim), administered once orally at the minimum recommended dose, was assessed in dogs experimentally infested with Ixodes hexagonus ticks. The study was a blinded, negative controlled clinical efficacy study using a randomized block design. Twenty-four Beagle dogs, 12 females and 12 males were enrolled. Dogs were randomly allocated either to the negative control group, or to one of the two treated groups. Infestations were performed with 50 adult I. hexagonus ticks on Days-2, 7 and 28. On Day 0, dogs in groups 2 and 3 were treated with NexGard® (afoxolaner) or NexGard Spectra® (afoxolaner + milbemycin oxime), respectively. Tick counts were conducted 48 hours after treatment (Day 2) and 48 hours after each subsequent infestation (Days 9 and 30). In both treated groups, afoxolaner was 100% effective against existing infestations (p < 0.0001). Regarding the re-infestations, the efficacy of afoxolaner was 100% on Day 9 for both products, 96.5% and 100% on Day 30 for NexGard® and NexGard Spectra® respectively. NexGard® and NexGard Spectra® chewable tablets administered once orally at the minimum recommended dose were highly effective against I. hexagonus infestations for the 4 weeks duration of the study.

Efficacy of two formulations of afoxolaner (NexGard\xae and NexGard Spectra\xae) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe

BackgroundA multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland.MethodsClient-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions.ResultsTreatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment.ConclusionsThis clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis.

Six-month field efficacy and safety of the combined treatment of dogs with Frontline Tri-Act\xae and NexGard Spectra\xae

BackgroundSafety and efficacy of the combined monthly use of spot-on fipronil 6.76% w/v / permethrin 50.48% w/v (Frontline Tri-Act®) and chewable tablets of afoxolaner 1.9% w/w / milbemycin oxime 0.4% w/w (NexGard Spectra®) in dogs was evaluated in a field study over a period of 6 months.MethodsForty-one healthy dogs living in highly endemic area for canine leishmaniosis and other canine vector borne diseases (VBD) were included in the study at the beginning of the Leishmania transmission season. Sixteen dogs were pet dogs living each in a single household; twenty-five dogs were hunting dogs living in three kennels. At inclusion, the dogs were ELISA (rapid test) negative for antibodies to Anaplasma, Borrelia, Ehrlichia, and for antigens of Dirofilaria. The dogs were also negative for blood microfilariae at the Knott’s test, and no clinical or haematological abnormalities were observed. Of the included dogs, six hunting, apparently healthy, dogs were ELISA (rapid test) positive to Leishmania, and some were naturally infected by gastrointestinal nematodes (58.5%) and/or infested by fleas (58.5%) and ticks (9.8%). All the included dogs were treated at Days 0, 28, 56, 84, 112 and 140, and followed-up for efficacy until the study end (Day 168).ResultsNo adverse events related to the two products, nor skin reactions, general signs, or changes in the haematological profile, were observed during the study. At Day 14, anthelminthic efficacy was 100% for Toxocara canis, Toxascaris leonina and Capillaria aerophila, while few hunting dogs were still shedding eggs of Trichuris vulpis (1/25 hunting dog) and Ancylostomatidae (9/25 hunting dogs). All pet dogs were nematode free at the end of the study. Hunting dogs were free of roundworms and whipworms. Twenty-four hours after the first treatment, 95.8% of the ectoparasite infested dogs were free from fleas and ticks. Ectoparasites were significantly controlled during the 6-month study period, with 100% efficacy on both fleas and ticks from Day 56 to Day 168. Blood and serum samples collected on Day 168 were tested for vector-borne pathogens using same methods of the inclusion and no new seroconversions or circulating blood microfilariae were observed.ConclusionsConcomitant use of Frontline Tri-Act® and NexGard Spectra® in dogs for six months was well tolerated. The combination was effective in controlling fleas, ticks, gastro-intestinal nematodes, and neither new seroconversion to the tested vector-borne pathogens nor blood microfilariae were detected in treated dogs at the end of the study.

Efficacy of Once-Monthly Doses of Oral Afoxolaner and Afoxolaner/Milbemycin Oxime in a Well-Controlled Study for the Treatment of Canine Generalized Demodicosis

The efficacy of oral treatment with chewable tablets containing afoxolaner 2.27% w/w (NexGard®, Merial, now part of Boehringer-Ingelheim) or 1.875% w/w of afoxolaner and 0.375% w/w milbemycin oxime (NexGard Spectra®, Merial, now part of Boehringer-Ingelheim) was each assessed in eight dogs diagnosed with generalized demodicosis in this parallel group designed, blinded, randomized, single center negative controlled, efficacy study. Afoxolaner at the therapeutic dose (as close as possible to 2.5 mg/kg) was administered to Group 2 dogs, and afoxolaner (as close as possible to 2.5 mg/kg) with milbemycin oxime at 0.5 mg/kg was administered to Group 3 dogs on Days 0, 28 and 56. All dogs were observed once daily for general health starting on Day -7 until Day 84. All dogs were clinically examined on Days -7, -2, 14, 28, 42, 56, 70 and 84. Dogs were weighed on Days -7, -2, 27, 55, and 84. Live mite counts (based on five scrapings per dog and occasion) and clinical assessments, including photographic documentation, were performed on Days -2, 28, 56 and 84. Three monthly treatments with NexGard or NexGard Spectra against generalized demodicosis in dogs were highly effective resulting in a 99.9% and 100% efficacy against mites, respectively. After treatment with NexGard, only three live mites were recovered in five scrapings in one dog on Day 84. After treatment with NexGard Spectra, no mites were recovered in any scraping on any dogs in this group by Day 84. Both treatments resulted in a marked reduction of skin lesions and >90% hair-regrowth at three months after the initial treatment. Reduction of live mite counts was consistent with reduction in the extent and severity of the skin changes. Although the arithmetic mean mite numbers in the negative control group decreased slightly during the study, infection persisted in 7 of the 8 control dogs until Day 84. Both treatment groups of dogs showed a marked improvement of the associated dermatologic signs with steady improvement over the three-month treatment period.

ПОРІВНЯЛЬНА ЕФЕКТИВНІСТЬ АКАРИЦИДІВ ЗА ДЕМОДЕКОЗУ СОБАК

The efficacy of the drugs Bravecto®, NexGard Spectra®, Advocate® and Amitrasin Plus to treat dogs having demodecosis have been studied in the comparative aspect. The aim of the work was to determine the efficacy of modern acaricidic drugs made on the basis of afoxalaner and fluralaner at different forms of the course of canine demodecosis by the comparative evaluation with the drugs that contain other active substances. The dogs with local form of demodecosis and low degree of skin invasion were divided into two experimental groups: group 1 and group 2. The dogs of group 1 were treated by Amitrasin plus that was put with the help of the saturated cotton disc, covering the area of the affected skin not less than 1 cm around it. Seven curative treatments were made (once a day, the period of treatment lasted 7 days). The dogs of group 2 were given the drug NexGard Spectra® at the dose of 2,5 mg afoxalaner and 0,5 mg milbemycin oxime per 1kg of body weight twice with the interval of 1 month. At the same time the dogs were injected Katosal at the dose of 1,0 ml once a day for 5 days. The dogs having more severe form of the disease - the generalized form of demodecosis were placed in the experimental groups 3 and 4. To treat the dogs of group 3 the tablets Bravecto® were used once at the dose of 25 mg of fluralaner/kg of body weight. The drug Advocate® was used to treat the dogs of group 4 three times with the interval of 28 days at the dose of 10 mg of imidakloprid / kg and 2,5 mg of moxidectin / kg of body weight. The affected areas of skin in the dogs of groups 3 and 4 were treated by novertin ointment twice a week for three weeks. Before the beginning of the treatment the acaroscopic investigation was carried out for 12 weeks with the interval of 28 days. When treating the localized form of demodecosis in the dogs the use of the tablets NexGard Spectra® twice was the most effective (93,3% - on the 28th day and 100% - on the 56th day). The seven – time treatments by Amitrasin-Plus were less effective (on the 28th day – 75%, on the 56 day – 83,3%). When treating the generalized form of demodecosis in the dogs the use of the drug Bravecto® in tablets and the drops spot on Advocate in the combination with the exterior treatments by novertin ointment was of high curative efficacy. It was 91,6 / 100% and 83,3% / 100% on the 28th day and on the 56th day from the beginning of the experiment, respectively. The results of the investigation have shown that it is necessary to use antimicrobial drugs when treating dogs having the generalized form of demodecosis. Taking into consideration the results of the experiment we think that it is expedient to choose the drugs in spite of the price allowing for the effectiveness of the active substance to treat dogs having demodecosis, in spite of the form of the invasion course.

Efficacy of afoxolaner plus milbemycin oxime chewable tablets (NexGard Spectra®, Merial) against adult Ancylostoma ceylanicum hookworm, in dogs

A fixed-combination chewable tablet incorporating afoxolaner plus milbemycin oxime (NexGard Spectra®, Merial) was tested in purpose-bred Beagle dogs for efficacy against adult Ancylostoma ceylanicum hookworms. Sixteen dogs were inoculated each by oral administration of approximately 500 infective larvae of A. ceylanicum. Seventeen days after inoculation, the dogs were weighed and allocated randomly to be treated with afoxolaner plus milbemycin oxime chewable tablets or to remain untreated. Commercial chewable tablets of different strength were combined to deliver doses as close as possible to the minimum effective dose of 2.5mg afoxolaner plus 0.5mg milbemycin oxime per kg body weight. Parasites were recovered and counted for determination of efficacy seven days after treatment.All eight dogs that had been left untreated were harboring adult A. ceylanicum (geometric mean, 317.8; range, 210–428) while only one and nine A. ceylanicum were recovered from two of the eight dogs treated with afoxolaner plus milbemycin oxime chewable tablets (geometric mean, 0.5; p<0.0001). Thus, 99.9% efficacy against induced infection of A. ceylanicum was obtained by the use of oral NexGard Spectra® at the minimum effective dose. Treatment with afoxolaner plus milbemycin oxime chewable tablets was well accepted and safe.

Preventive efficacy of NexGard Spectra® against Dipylidium caninum infection in dogs using a natural flea (Ctenocephalides felis) infestation model.

The efficacy of a monthly oral endectocide product, NexGard Spectra® (Merial), a combination of afoxolaner and milbemycin oxime, was evaluated in a flea (Ctenocephalides felis) challenge model for the prevention of Dipylidium caninum tapeworm infection in dogs. The efficacy of treatment with NexGard Spectra® was assessed in 10 dogs following weekly flea infestation with metacestode naturally infected fleas and compared with that in 10 untreated control dogs. The 100 fleas deposited weekly on each dog were not removed until Day 35, allowing enough time for their ingestion. The microscopical analysis of 30 fleas from the flea batches before each weekly challenge demonstrated that 10–33% of the fleas were infected by D. caninum cysticercoid larvae. The arithmetic mean flea count recorded was 47.7 for the 10 untreated dogs and 0 for the 10 treated dogs at Day 35. Based on the daily collection of expelled D. caninum proglottids by dogs during the 70 days of the study, 70% (7/10) of the control dogs and 0% (0/10) of the treated dogs were infected with D. caninum (p < 0.0031). Through its efficacy against fleas, NexGard Spectra® treatment provided indirect prevention of D. caninum infestation. No treatment-related adverse events were observed in dogs during this study.

Efficacy against nematode infections and safety of afoxolaner plus milbemycin oxime chewable tablets in domestic dogs under field conditions in Europe.

Afoxolaner (AFX) plus milbemycin oxime (MO) combination chewable tablets (NexGard Spectra®, Merial) were evaluated for safety and efficacy against naturally acquired nematode infections in domestic dogs in a multi-centre, positive control, blinded field study using a randomized block design based on the order of presentation for allocation. In total, 408 dogs confirmed positive for naturally acquired infections of intestinal nematodes by pre-treatment faecal examination were studied in ten countries in Europe (Albania, Austria, Bulgaria, France, Germany, Hungary, Italy, Lithuania, Romania and Slovakia). Pre-treatment faecal examination revealed Toxocara, Toxascaris, hookworm, Trichuris and/or Capillaria nematode infections in 134, 30, 223, 155 and 14 dogs, respectively. Dogs were allocated to one of two treatment groups in a ratio of 1, AFX + MO chewables (≥2.5mg AFX + ≥0.5mg MO per kg body weight, according to dose bands; 207 dogs), and 1, MO plus praziquantel (PRZ) chewables (Milbemax®, Novartis; ≥0.5mg MO + ≥5mg PRZ per kg body weight, according to the manufacturer's instructions; 201 dogs) and treated once. For evaluation of efficacy based on reduction of faecal nematode egg counts, two faecal samples, one collected prior to treatment and one collected 9 to 21days after treatment, were examined using modified McMaster techniques. For evaluation of systemic safety, dogs were examined by a veterinarian before treatment administration and at study end, and dog owners observed the health status of their dogs until the end of the study and reported any abnormal observation. For dogs treated with AFX + MO chewables, the efficacy was 99.7, 99.7, 97.2, 99.7 and 99.7% for Toxocara, Toxascaris, hookworm, Trichuris and Capillaria, respectively; and the efficacy was 99.5, 99.4, 94.3, 99.9 and 98.0%, respectively, for the MO + PRZ-treated dogs (p ≤ 0.002 for all nematodes and both treatments). For Toxocara, hookworm and Trichuris, non-inferiority analysis demonstrated that the efficacy of AFX + MO chewable tablets was equal to or better than that of MO + PRZ. In spite that both treatments were ≥98% efficacious against Toxascaris and Capillaria, a hypothesis of non-inferiority for both genera could not be established due to the low number of dogs infected with these parasites. No treatment-related adverse experiences were observed throughout the study. For both treatments, all dogs were given a systemic safety score of 'excellent' apart from one dog in each treatment group which received a score of 'acceptable'. AFX + MO combination chewables were shown to be safe and demonstrated a high level of efficacy when administered once to dogs infected with a broad range of parasitic nematodes under field conditions.

Evaluation of the efficacy of monthly oral administration of afoxolaner plus milbemycin oxime (NexGard Spectra®, Merial) in the prevention of adult Spirocerca lupi establishment in experimentally infected dogs

The nematode Spirocerca lupi (Rudolphi, 1809) is widely distributed but mostly occurs sporadically with stable populations only in certain geographic areas. This helminth mainly infects dogs and wild canids. Primary pathology relates to migration of third stage larvae (L3) damaging the thoracic aorta and establishment of adults in nodules in the oesophagus. The objective of the present study was to evaluate the efficacy of milbemycin oxime in combination with afoxolaner (NexGard Spectra®, Merial), administered monthly, in preventing establishment of adult worms after experimental infection. Two groups consisting of eight animals each were experimentally infected with 15 L3 on Days −28, −14 and −2, respectively (45 L3 per animal in total). Group 1 dogs served as untreated (negative) control, whereas animals in group 2 were treated with NexGard Spectra® at a minimum dose of 0.5mg/kg milbemycin oxime on Day 0 and from then onwards every 28 days up to Day 140 (six treatment occasions). Endoscopy was performed on Day 112 and for some animals also Day 140. Necropsy for worm recovery and nodule/lesion scoring was performed on Day 168. All eight animals in the control group (group 1) presented with 1–3 nodules and worm counts ranging from 9 to 41. Six animals in the NexGard Spectra® group presented with 1–4 nodules and worm counts ranging from 1 to 5. Significantly (p<0.05) fewer worms were collected from treated animals in the treated group (geometric mean 1.7) versus the negative control group (geometric mean 22.0) with 92.3% efficacy calculated. There was no significant (p>0.05) difference between groups with reference to number of nodules in the oesophagus. However, nodules in the control group were significantly (p<0.05) larger than those in the treated group.Number and size of lesions in the dorsal aorta did not differ statistically between groups 1 and 2. Because NexGard Spectra® was administered 28 days after onset of inoculation, migrating and developing L3 caused damage to the aorta wall of animals in the treated group. Milbemycin oxime (administered as NexGard Spectra®) demonstrated effectiveness in reducing infection with adult Spirocerca lupi worms in the oesophagus.

Efficacy of oral afoxolaner plus milbemycin oxime chewables against induced gastrointestinal nematode infections in dogs

The efficacy of oral afoxolaner plus milbemycin oxime combination chewables against induced gastrointestinal nematode infections in dogs was evaluated in six separate studies. Two studies were performed to evaluate the efficacy of the product against Toxocara canis, two studies evaluated the efficacy against Toxascaris leonina, one study evaluated the efficacy against Ancylostoma braziliense, and one study evaluated the efficacy against Ancylostoma caninum. In the A. caninum study, the efficacy of milbemycin oxime alone and afoxolaner alone was also evaluated. Dogs in all studies were inoculated with infective eggs or larvae and confirmed to have patent infections based on a fecal examination prior to allocation to study group and treatment.Each study utilized a randomized block design with blocks based on pre-treatment body weight. All dogs were assigned to blocks based on body weight, and then each dog within a block was randomly assigned to treatment group. There were two groups of 10 dogs each in the T. canis, T. leonina, and A. braziliense studies: 1) an untreated (control) group and 2) a group treated with afoxolaner plus milbemycin oxime chewables (NexGard Spectra®, Merial). This group was treated at a dose as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime (2.5mg+0.5mg per kg body weight, respectively) once on Day 0 using whole chews. There were four groups of 10 dogs each in the A. caninum study: 1) untreated (control), 2) NexGard Spectra® as described above, 3) milbemycin oxime alone (dose of at least 0.5mg per kg of body weight) and 4) afoxalaner alone (dose of at least 2.5mg per kg body weight). For parasite recovery and counts, dogs were euthanized humanely and necropsied seven days after treatment.The efficacy of the afoxolaner plus milbemycin oxime combination was ≥98% against T. canis, ≥95.8% against T. leonina, and 90.2% against A. braziliense. Efficacy of the combination against A. caninum was 99.7%, while the efficacy of milbemycin oxime alone was 99.6% and the efficacy of afoxolaner alone was 2.1%. Dogs treated with afoxolaner plus milbemycin oxime chewables had significantly (p≤0.0002) fewer nematodes than the untreated controls in all studies. There were no adverse events or other health problems that were related to treatment with Nexgard Spectra® in these studies.The results of these controlled studies demonstrate the high efficacy of the afoxolaner plus milbemycin oxime chewables against a broad range of canine intestinal nematode infections.

Efficacy of oral afoxolaner plus milbemycin oxime chewables against induced infestations with Dermacentor reticulatus in dogs.

The efficacy of afoxolaner plus milbemycin oxime (AFX + MO) combination chewables (NexGard Spectra®, Merial) and AFX single-entity chewables (NexGard®, Merial) against induced infestations with Dermacentor reticulatus ticks was evaluated in dogs. Thirty dogs were assigned to blocks of three animals each based on pre-allocation tick counts and were randomly allocated to one of three groups: untreated (control), treated with a combination of AFX + MO chewables to be as close as possible to the minimum effective dose of AFX + MO (2.5 + 0.5mg per kg body weight), and treated with a combination of NexGard® chewables to be as close as possible to the minimum effective dose of AFX (2.5mg per kg body weight). Treatments were administered orally once on day 0. Starting 2days before treatment administration, each dog was infested with approximately 50 ticks weekly for six consecutive weeks. Live ticks were counted at ∼48h post-treatment (removal count) and at ∼48h (in situ counts) and ∼72h (removal counts) following each post-treatment infestation. Treatment with both AFX + MO and NexGard® chewables rapidly eliminated the existing tick infestations (100% efficacy) within 2days following treatment administration. Weekly re-infestations were controlled for a minimum of 5weeks with the efficacy ranging from 92.2 to 99.7% based on ∼48h post-treatment in situ counts and between 99.0 and 100% based on ∼72h post-treatment removal counts (p < 0.0001 at each occasion). This study demonstrated a high efficacy of both AFX + MO chewable and NexGard® chewable treatments against infestations of dogs with D. reticulatus ticks for at least 5weeks. In addition, this study indicated no interference between the two compounds with respect to the acaricidal activity provided by AFX.

Efficacy of afoxolaner plus milbemycin oxime chewable tablets against naturally acquired intestinal nematodes in dogs

The efficacy of oral afoxolaner plus milbemycin oxime combination chewable tablets (NexGard Spectra®, Merial) against naturally acquired intestinal nematode infections in dogs was evaluated in six negative control, blinded studies including a total of 114 dogs. Dogs were selected based on a pre-treatment fecal examination indicating patent infections with hookworms (two studies), Toxocara or Toxascaris ascarids (one study each) or Trichuris whipworms (two studies).In each study, dogs were assigned to blocks of two animals each, based on decreasing pre-treatment body weight and were randomly allocated to one of two groups consisting of eight, nine or 10 dogs: untreated (control) or treated with the combination chewable tablet formulation. Chewable tablets were combined to provide doses of actives as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime, i.e., 2.5mg/kg body weight and 0.5mg/kg body weight, respectively, once on Day 0. For parasite recovery and count, dogs were euthanized humanely and necropsied seven or eight days after treatment.A single treatment with afoxolaner plus milbemycin oxime chewable tablets provided 94.8% and 90.9% efficacy against adult Ancylostoma braziliense and A. caninum, respectively, 97.8% and 99.4% efficacy against adult Toxocara canis and Toxascaris leonina, respectively, and ≥98.3% efficacy against adult Trichuris vulpis. Compared to untreated controls, nematode counts of the treated dogs were significantly reduced (F-test; p<0.002). In addition, analysis of the pooled data across studies revealed that treatment with afoxolaner plus milbemycin oxime chewable tablets reduced adult Uncinaria stenocephala burdens by 74.9% (p=0.002). All dogs tolerated the treatment well based on clinical observations post-treatment and daily clinical observations. No adverse experiences or other clinical problems related to the treatment were observed throughout the studies.The results of this series of controlled studies demonstrated high efficacy and excellent acceptability and safety of the afoxolaner plus milbemycin oxime chewable tablets when administered for treatment of a broad range of canine intestinal nematode infections.