Steve Nanchen

Laboratory evaluations of the immediate and sustained efficacy of lotilaner (Credelio™) against four common species of ticks affecting dogs in North America

BackgroundEffective control of tick infestations on dogs is important to reduce the risk of transmission of bacterial, viral, and protozoal pathogens. Laboratory studies were initiated to determine the efficacy of lotilaner against common ticks infesting dogs in the United States.MethodsEight studies investigated the efficacy of lotilaner against ticks. In two studies dogs were infested with both Dermacentor variabilis and Rhipicephalus sanguineus: one additional study was completed for each of these species. Two studies assessed infestations with Amblyomma americanum and two with Ixodes scapularis. In all studies, dogs were ranked and blocked by counts from pre-treatment infestations and randomly allocated, at least eight per group, to be treated orally with lotilaner (minimum dose rate 20xa0mg/kg), or to be untreated controls. Treatments were administered on Day 0, within 30xa0min after dogs were fed. In all studies, infestations were performed with 50 adult ticks on Days -2, 7, 14, 21 and 28, and also on Day 35 for R. sanguineus, D. variabilis and I. scapularis. Tick counts were completed 48xa0h after treatment or after each subsequent challenge. An adequate infestation was defined as at least 25% of the infestation dose recovered from each of at least six control animals at each evaluation. Efficacy calculations for the primary objective were based on geometric means.ResultsIn all studies, lotilaner was 100% effective against existing infestations. For post-treatment assessments, on only two occasions did efficacy fall below 99%: in one D. variabilis study efficacy was 98.0% on Day 35 and in one I. scapularis study efficacy on Day 16 was 98.4%. Only mild and transient adverse events were observed, and none were considered to be related to treatment.ConclusionLotilaner was completely effective against existing infestations with four common species of ticks, D. variabilis, R. sanguineus, A. americanum and I. scapularis, that affect dogs in North America, with at least 4xa0weeks efficacy of 98.0% or more against subsequent challenge infestations. These results show that lotilaner is a highly effective isoxazoline that offers sustained efficacy against ticks through and beyond the one-month end-of-dose treatment interval.

Assessment of the onset of lotilaner (Credelio™) speed of kill of fleas on dogs

BackgroundLotilaner (Credelio™) is the newest member of the novel isoxazoline chemical class to be developed to treat canine ectoparasitism. Administered orally, lotilaner is rapidly absorbed with peak blood levels occurring within 2 h post-treatment. A study was undertaken to determine the earliest onset of lotilaner’s efficacy against existing flea infestations.MethodsFrom 72 Beagles, 64 qualifying dogs were ranked in descending order of flea counts from a Day -8 infestation and placed into eight blocks. Within blocks, eight dogs were randomly allocated among eight groups: Groups 1 to 4 were treated orally with lotilaner, at as close as possible to the minimum dose rate of 20xa0mg/kg within 30 (± 5) minutes after feeding; Groups 5 to 8 were untreated controls. All dogs were infested with 100xa0±xa05 fleas on Day -2, and whole-body flea counts were completed at 30xa0min and one, two and 8 h after treatment. Efficacy calculations were based on arithmetic and geometric means if an adequate infestation (at least six of eight untreated dogs with a flea retention of ≥xa050%) was demonstrated in the equivalent control group.ResultsAdequate infestations were established in all control groups. At 30xa0min and 1 h post-treatment, relative to the matching untreated control group, there were no significant reductions in mean flea counts in lotilaner-treated dogs, although moribund fleas were evident at 1 h post-treatment. At 2 h after treatment, compared with the equivalent control group, the geometric mean flea count reduction in the lotilaner group was 64.0% (t(7)xa0=xa02.86, Pxa0=xa00.0242). At 8 h after treatment, lotilaner efficacy was 99.6%. There were no treatment-related adverse events.ConclusionThis study demonstrates that lotilaner flavored chewable tablets are well tolerated and begin to kill fleas within 2 h of treatment, achieving 99.6% efficacy within 8 h. Lotilaner can therefore be used to quickly alleviate the flea irritation that arises from existing infestations.

A randomized, controlled field study to assess the efficacy and safety of lotilaner flavored chewable tablets (Credelio™) in eliminating fleas in client-owned dogs in the USA

BackgroundPreclinical studies have shown that the novel isoxazoline, lotilaner (Credelio™, Elanco) administered orally to dogs, produces rapid flea and tick knockdown and sustained speed of kill for at least a month post-treatment with a wide safety margin. A field study was undertaken to validate pre-clinical results.MethodsDogs were enrolled at 10 veterinary clinics across the United States. Qualifying households containing up to three dogs and one primary dog with at least 10 fleas were randomized 2:1 to receive lotilaner (Credelio™, Elanco) at the recommended minimum dose of 20xa0mg/kg, or afoxolaner (Nexgard®, Merial), administered per label, to give a minimum dose of 2.5xa0mg/kg. Treatments were dispensed on Days 0, 30 and 60 for administration by owners; all household dogs received the same treatment as the primary dog. Post-enrollment flea and tick counts were made on primary dogs on Days 30, 60 and 90, and all dogs were assessed for tablet palatability and safety.ResultsFor efficacy assessments, data were used from 111 lotilaner-treated dogs and 50 afoxolaner-treated dogs; for safety, 197 and 86 dogs, respectively. Percent reductions from baseline in geometric mean flea counts for the lotilaner group were 99.3, 99.9 and 100% on Days 30, 60 and 90, respectively, and for afoxolaner 98.3, 99.8 and 99.8% (Pu2009<u20090.001, both groups, all days). On Day 90, 100% of lotilaner-treated dogs and 93% of afoxolaner-treated dogs were flea-free. Too few ticks were present to allow assessment. There were no differences in palatability between products (Pu2009=u20090.2132), with, respectively, 94% and 96% of lotilaner and afoxolaner treatments accepted when offered by hand, in an empty food bowl or with food. Both treatments were well tolerated, alleviating clinical signs of flea allergy dermatitis (FAD) in dogs affected at enrollment.ConclusionA single owner-administered lotilaner treatment was greater than 99% effective in reducing mean flea counts within 30xa0days. Three consecutive monthly lotilaner treatments resulted in a 100% reduction in flea infestations, and a substantial reduction in signs of FAD. Lotilaner flavored tablets were readily accepted under field conditions. The absence of treatment-related adverse events confirms the safety of lotilaner in dogs.

Laboratory evaluations of the immediate and sustained effectiveness of lotilaner (Credelio™) against three common species of ticks affecting dogs in Europe

BackgroundThere is a continuing need for novel approaches to tick control in dogs. One such approach lies in the ability of lotilaner (Credelio™), an isoxazoline with a rapid onset of action, to provide sustained efficacy against ticks. Two studies were undertaken to confirm lotilaner’s efficacy, at the minimum dose rate of 20xa0mg/kg, against the three most common tick species in Europe.MethodsIn each of two studies, 16 Beagle dogs, at least 6 months old, were ranked and blocked by tick counts from infestations placed approximately 1 week before treatment. Within blocks, dogs were randomized to receive either lotilaner flavoured chewable tablets at as close as possible to, but not less than the minimum dose rate of 20xa0mg/kg, or to be sham-treated controls. Study 1 assessed lotilaner efficacy against concurrent infestations with 50 (± 6) Rhipicephalus sanguineus and 70 (± 6) Ixodes ricinus; Study 2 infestations were with 50 (± 2) Dermacentor reticulatus. Infestations were performed on Day -2 with counts on Day 2, 48 (± 2) hours post-treatment. Post-treatment infestations were performed on Days 7, 14, 21, 28 and 35, and ticks were counted 48 (±2) hours post-infestations. Efficacy was determined by the percent reduction in mean live tick counts.ResultsControl group infestations for each tick species were adequate for assessing lotilaner efficacy at all assessment times. On Day 2 no live ticks were found on any lotilaner-treated dog. For subsequent counts, in Study 1 lotilaner was 100% effective in eliminating live I. ricinus and R. sanguineus on all but two occasions for each tick; on each of those occasions efficacy was sustained at greater than 98.0%. In Study 2, except for a single unattached live tick found on Day 16, efficacy against D. reticulatus was 100% at every post-treatment assessment.ConclusionThe high and sustained efficacy against the three common species of ticks in Europe, R. sanguineus, I. ricinus and D. reticulatus, demonstrates that lotilaner can be a valuable tool in the treatment of canine tick infestations. Lotilaner flavoured chewable tablets were well tolerated and effectiveness was sustained through at least 35xa0days.

A randomized, controlled field study to assess the efficacy and safety of lotilaner (Credelio™) in controlling fleas in client-owned cats in Europe.

BackgroundThere is a continuing need for novel approaches to tick infestations treatment and control in cats. Lotilaner, an isoxazoline with rapid onset of action, has proven its efficacy against ticks in laboratory studies. A study was undertaken to confirm lotilaner’s efficacy and safety in client-owned cats, at the minimum dose of 6.0 mg/kg, against the most common ticks infesting cats in Europe.MethodsTwenty clinics in Germany, Hungary and Portugal participated in the study. Households with no more than three cats were randomized 2:1 to a lotilaner or fipronil group. The first household cat with at least three live, attached ticks was the primary cat. Treatments were dispensed on days 0, 28 and 56 for owner administration. Tick counts were performed on days 0, 7, 14, 21, 28, 42, 56, 70 and 84 (primary cats) and supplementary cats were assessed for safety only, on days 28, 56 and 84. Efficacy was assessed by comparing mean day 0 live attached tick counts with subsequent counts.ResultsMost frequently retrieved ticks were Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus, with Ixodes hexagonus also present. In the lotilaner group (n = 112) efficacy (based on geometric mean tick counts) was between 98.3–100%. For fipronil (n = 57), efficacy was between 89.6–99.6%, with live attached ticks present on some cats at all time points. Mean tick counts in lotilaner-treated cats were significantly lower than in fipronil-treated cats on days 21, 28, 42 and 56 (P < 0.05). The mean percent efficacy over all post-enrolment visits was 99.6% and 96.4% (lotilaner and fipronil group, respectively), (P < 0.0001). Lotilaner was superior to fipronil for efficacy averaged over all time points (P < 0.0001) and on individual assessment days (day 14 to 70, P < 0.0394); it was non-inferior to fipronil on the other days. Owners successfully administered all treatments, and both products were well tolerated.ConclusionsCredelioTM was effective and safe for the treatment of tick infestations in client-owned cats. Efficacy lasted one month and lotilaner was superior to fipronil on most assessment days. Cure rates ranged between 94.5–100% for lotilaner and 68.4–98.2% for fipronil.

Laboratory evaluation of the speed of kill of lotilaner (Credelio™) against Ixodes ricinus ticks on dogs

BackgroundWith the geographical expansion of tick species and increased recognition of pathogens they transmit, there is a requirement for safe and rapidly effective control measures for dogs. Lotilaner, a novel isoxazoline, is rapidly absorbed following administration of a flavored chewable tablet formulation (Credelio™), providing at least 98% efficacy for at least 1xa0month following assessments at 48xa0h post-treatment, and following subsequent challenges. A study was conducted to determine the speed with which lotilaner kills ticks.MethodsFrom 38 dogs, the 32 with the highest Ixodes ricinus counts from a Day -4 infestation were randomized among four groups: two groups were untreated controls, two received lotilaner tablets at a minimum dose rate of 20xa0mg/kg. Infestations with I. ricinus were performed on Days -2, 7, 14, 21, 28 and 35. Counts were completed 4 and 8xa0h post-treatment (Day 0), and 8 and 12xa0h following subsequent infestations. All live ticks were incubated for 24xa0h following removal from study dogs.ResultsAt 4xa0h post-treatment, there was a 69.8% reduction in geometric mean live tick counts in treated dogs compared to controls. After incubation, the reduction increased to 97.2%. At 8xa0h after treatment, pre- and post-incubation reductions were 99.2 and 100%, respectively. Following post-treatment challenges, post-incubation efficacy through Day 28 at 8 and 12xa0h was at least 94.3 and 98.0%, respectively, and was 85.7 and 94.2% at 8 and 12xa0h after the Day 35 challenge. Mean live tick counts in the lotilaner groups were significantly lower than in the control groups at all assessments through Day 35 at 8 (t(7)xa0≥xa09, Pxa0<xa00.0001, Days 0 to 28; t(7)xa0=xa03.54, P ≤ 0.0095, Day 35) and 12xa0h post-treatment and after subsequent infestations (t(7)xa0≥xa010, Pxa0<xa00.0001, all days). There were no treatment-related adverse events.ConclusionLotilaner at a minimum dose rate of 20xa0mg/kg began to kill ticks on dogs within 4xa0h of treatment and efficacy was 100% within 8xa0h. Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35xa0days. By quickly killing ticks that infest dogs, lotilaner has potential to help limit the transmission of tick-borne pathogens.

Assessment of the speed of flea kill of lotilaner (Credelio™) throughout the month following oral administration to dogs

BackgroundLotilaner (Credelio™, Elanco), a novel isoxazoline, is a systemic insecticide and acaricide that is rapidly absorbed following oral administration to dogs and has a half-life of 30xa0days. As part of a development program, studies were undertaken to investigate lotilaner’s initial and sustained efficacy and speed of kill against fleas.MethodsFour studies were conducted to evaluate the onset of lotilaner’s speed of flea knockdown at the time of treatment, and to determine the sustained speed of flea kill (SOK) up to 35xa0days post-treatment. Each study assessed one or two specific time points (4, 6, 8 and 12xa0h) post-treatment and following weekly re-infestations. In each study, dogs were randomised to a lotilaner or an untreated group based on pre-administration flea counts, and before treatment were infested with adult Ctenocephalides felis. Dogs randomised to a lotilaner group received a single treatment on Day 0, at the minimum recommended dose rate of 20xa0mg/kg, 30 (± 5) minutes after being fed. Efficacy was calculated using geometric, and arithmetic mean flea counts in treated versus untreated groups.ResultsOn Day 0, lotilaner efficacy was 89.9% at 4xa0h, 99.2% at 6xa0h, 99.9% at 8xa0h, and 100% at 12xa0h post-treatment. At each weekly assessment, lotilaner efficacy at 4xa0h remained at >xa097%, at 8xa0h remained at >xa099%, and at 12xa0h remained at 100% through Day 35. Across all studies, there were no treatment-related adverse events.ConclusionLotilaner’s rapid flea knockdown immediately following treatment and sustained SOK through 35xa0days post-treatment offers a new solution for helping to eliminate the health risks that accompany flea infestations on dogs. The consistency of the rapid, sustained flea SOK demonstrated in these studies generates confidence that monthly use of lotilaner in dogs can be valuable in disrupting the flea life cycle in a contaminated environment, and that newly acquired fleas will die quickly, thereby reducing the discomfort of flea bites. The sustained lotilaner SOK also provides confidence that there will be no “end-of-dose” resurgence in flea burdens with the potential accompanying consequence of flares in flea-bite hypersensitivity.

Two randomized, controlled studies to assess the efficacy and safety of lotilaner (Credelio™) in preventing Dermacentor reticulatus transmission of Babesia canis to dogs

BackgroundDogs worldwide are at risk of Babesia spp. infections. Preventive efficacy of lotilaner tablets (Credelio™, Elanco) against Babesia canis was evaluated in two studies.MethodsSixteen dogs in Study 1 and 12 dogs in Study 2, all seronegative and polymerase chain reaction (PCR) negative for B. canis, were randomized to a sham-treated control group or a lotilaner (20–43xa0mg/kg) treatment group, administered on Day 0 (Study 1: nxa0=xa08/group; Study 2: nxa0=xa06/group). Dogs were each infested with 50 Dermacentor reticulatus, a percentage of which (Study 1: 8.0–30.0%; Study 2: 12.2%) were infected with B. canis, in Study 1 on Days 2, 7, 14, 21 and 28, and in Study 2 on Day 28. Ticks were removed and counted on Day 30 in Study 1, and Day 34 in Study 2. Blood was collected for Babesia detection via smear, PCR and immunofluorescence assay (IFA) in Study 1 on Day 2, then approximately weekly through Day 56, and in Study 2 at weekly intervals between Days 28 to 49, and on Days 63 and 91. Additional samples were collected from dogs with body temperaturexa0>xa039.4xa0°C (measured three times weekly, from Days 7 to 56 in Study 1 and from Days 35 to 56 in Study 2) and positive for B. canis on blood smear. Dogs with confirmed infections were rescue-treated, removed from the study and, in Study 1, replaced.ResultsAcross both studies B. canis infection of ticks ranged between 8.0–30.0%. In Study 1, all control dogs were positive for B. canis on blood smear and PCR on Day 10 and IFA on Day 21; on Day 21 seven of eight replacement control dogs were B. canis-positive; no replacement dogs were B. canis-positive following tick removal on Day 30. In Study 2, all control dogs were B. canis-positive on Day 56. All lotilaner-treated dogs remained B. canis-negative at all assessments in both studies.ConclusionLotilaner efficacy was 100% in preventing establishment of B. canis infection, despite post-treatment challenge with infected ticks on Days 2, 7, 14, 21 and 28.

Laboratory evaluation of the efficacy and speed of kill of lotilaner (Credelio™) against Ctenocephalides felis on cats

BackgroundLotilaner is approved for dogs as a chewable tablet formulation. It has separately been developed for oral administration in cats (Credelio™ chewable tablets for cats) to meet the need for an easy to use, safe and rapidly effective parasiticide and as an alternative to topical products. This paper describes two pivotal laboratory studies assessing the efficacy and speed of kill of lotilaner in cats against Ctenocephalides felis fleas following a single oral administration, at the minimum recommended dose rate of 6 mg/kg.MethodsTwo GCP (Good Clinical Practice), blinded, randomized, negative-controlled, parallel-groups, laboratory studies were performed. In both studies, lotilaner was administered once, per os, at the minimum recommended dose of 6 mg/kg. Study 1 evaluated the efficacy of lotilaner tablets for cats against adult C. felis in experimentally infested cats, 24 h after treatment and after new weekly infestations, until day 35. Study 2 evaluated the speed of kill of lotilaner against C. felis, in cats, 8 and 12 h after treatment and after each subsequent weekly infestation, through day 35. In both studies, for each assessed time point, animals were randomized 1:1 to a lotilaner-treated or a contemporaneous negative control group of 8 cats each.ResultsIn both studies, the infestation in the control groups was adequate at all assessment times. In Study 1, efficacy at 24 h was 100% at all time points. In Study 2, efficacy was ≥ 97.4% at the 8 h and ≥ 98.6% at the 12 h time point, through one month. Lotilaner was well tolerated, with no product-related adverse events reported.ConclusionsLotilaner administered orally to cats at the minimum recommended dose rate of 6 mg/kg was effective as early as 8 hours post-administration and at 8 hours after subsequent weekly infestations of adult C. felis for at least one month. The product was well-tolerated.

A randomised, blinded, controlled field study to assess the efficacy and safety of lotilaner tablets (Credelio™) in controlling fleas in client-owned dogs in European countries

BackgroundLotilaner is a novel isoxazoline developed for oral administration to dogs. In laboratory studies, lotilaner was shown to be safe and to produce a rapid flea and tick knockdown, with a sustained speed of kill for at least a month post-treatment. A study was undertaken to demonstrate the efficacy, safety and palatability of three monthly doses of lotilaner flavoured chewable tablets (Credelio™, Elanco) in controlling fleas under field conditions in Europe.MethodsDogs were enrolled at 17 veterinary clinics across Germany, Hungary and Portugal. Qualifying households having no more than three dogs and one primary dog with at least five fleas was randomised 2:1 to a lotilaner (minimum dose rate 20xa0mg/kg) or a topical fipronil group (administered per label). There were 128 and 64 households allocated to the lotilaner and fipronil groups, respectively. Treatments were dispensed to owners on Days 0, 28 and 56; supplementary household dogs received the same treatment as the primary dog. Post-enrollment flea counts and flea allergy dermatitis (FAD) assessments were made on primary dogs on Days 14, 28, 56 and 84. Efficacy calculations were based on geometric mean percent reductions of live flea counts versus pre-treatment counts on Day 0. The safety and palatability of lotilaner tablets were also assessed.ResultsLotilaner efficacy was 99.1, 99.5, 99.9 and 99.8% on Days 14, 28, 56 and 84, respectively. Corresponding reductions for fipronil were 93.4, 91.2, 94.4 and 97.0%. Lotilaner was superior to fipronil at all post-Day 0 assessments (t(186)xa0≥xa03.43, Pxa0≤ 0.0007). At every post-treatment assessment, at least 90% of lotilaner-treated dogs were flea-free (98.4% on Day 84); fewer than 90% of fipronil group dogs were flea-free on the same time points. Lotilaner flavoured chewable tablets were palatable, and both products were well tolerated. Lotilaner alleviated or eliminated clinical signs of FAD, including pruritus.ConclusionsUnder field conditions in Europe, lotilaner flavoured chewable tablets were greater than 99% effective in eliminating fleas from dogs at the first post-treatment assessment (Day 14). Efficacy was maintained through Day 84, with corresponding improvements in FAD. Lotilaner tablets were palatable and safe and provided superior flea control to fipronil.