Heartworm Prevention
In two well-controlled laboratory studies, a single oral dose of Credelio Quattro was 100% effective in preventing the development of adult D. immitis in dogs inoculated with infective larvae 30 days before administration.
In a well-controlled U.S. field study consisting of 156 dogs administered Credelio Quattro and 149 administered an active control for 11 consecutive months, no dogs treated with Credelio Quattro tested positive for heartworm disease. All dogs treated with Credelio Quattro were negative for D. immitis antigen and blood microfilariae at study completion on Day 330.
Intestinal Nematode and Cestode Treatment and Control
In well-controlled laboratory studies, a single dose of Credelio Quattro was ≥ 97.0% effective against immature adult and adult Toxocara canis; adult Toxascaris leonina; fourth stage larvae, immature adult, and adult Ancylostoma caninum; and adult Uncinaria stenocephala infections.
In a 10-day multi-center US field study, 72 dogs administered a single dose of Credelio Quattro and 37 dogs administered a single dose of an active control were evaluable for effectiveness; Credelio Quattro reduced Ancylostoma caninum fecal egg counts 99.9% compared to pre-treatment.
In well‐controlled laboratory studies, a single dose of Credelio Quattro was 100% effective against Echinococcus granulosus. In separate well-controlled laboratory studies, praziquantel alone was 100% effective against Echinococcus granulosus, Dipylidium caninum, and Taenia pisiformis.
Flea Treatment and Prevention
In a well-controlled laboratory study, Credelio Quattro was 100% effective against adult fleas 24 hours after administration or infestation for 36 days. In a separate laboratory study, lotilaner alone began to kill fleas 4 hours after administration or infestation, with greater than 99% of fleas killed within 8 hours after administration or infestation for 35 days.
In a well-controlled laboratory study, lotilaner alone killed fleas before they could lay eggs, thus preventing subsequent flea infestations for 30 days after the start of treatment of existing flea infestations.
In a well-controlled U.S. field study conducted in households with existing flea infestations of varying severity, flea reductions of 99.5% to 100% were observed over the course of three monthly treatments with lotilaner alone. Dogs with signs of flea allergy dermatitis showed improvement in erythema, papules, scaling, alopecia, dermatitis/pyodermatitis, and pruritus as a direct result of eliminating fleas.
Tick Treatment and Control
In well-controlled laboratory studies, Credelio Quattro was ≥ 97.1% effective against Rhipicephalus sanguineus and Haemaphysalis longicornis ticks 48 hours after administration or infestation for 32 days. In well-controlled laboratory studies, lotilaner alone was > 97% effective against Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, and Rhipicephalus sanguineus ticks 48 hours after administration or infestation for 30 days.
In a well-controlled European laboratory study, lotilaner alone started killing Ixodes ricinus ticks within 4 hours after administration.
In two separate, well-controlled laboratory studies, Credelio Quattro was effective at preventing Borrelia burgdorferi infections after dogs were infested with Ixodes scapularis vector ticks.
REASONABLE EXPECTATION OF EFFECTIVENESS
New World Screwworm (NWS) Myiasis Treatment
A reasonable expectation of effectiveness may be demonstrated based on evidence such as, but not limited to, pilot data in the target species or studies from published literature.
Credelio Quattro-CA1 is conditionally approved pending a full demonstration of effectiveness.
Additional information for Conditional Approvals can be found at
www.fda.gov/animalca.
A reasonable expectation of effectiveness for Credelio Quattro-CA1 is based on a study conducted by do Vale et al.1 that evaluated the effectiveness of Credelio (lotilaner) alone for the treatment of naturally acquired NWS myiasis in dogs in eleven client-owned dogs in Brazil. All dogs received a single oral administration of lotilaner at doses ranging from 23.9 to 40.9 mg/kg body weight, following the dose bands for the approved flea and tick indications. The study did not include a control group.
Dogs were observed at 2- and 6- hours post-treatment for larval expulsion, with remaining dead larvae mechanically removed at 24 hours.
The study demonstrated 100% overall effectiveness (expulsion plus larvicidal activity) against Cochliomyia hominivorax larvae at 24 hours, with larval expulsion rates of 80.5% and 93% at 2 and 6 hours, respectively. The mean larvicidal effectiveness was 41.1% at 24 hours, suggesting that the overall effectiveness at 24 hours was primarily driven by larval expulsion rather than direct killing.
The extrapolation of effectiveness data from Credelio to Credelio Quattro-CA1 is supported by use of the same approved lotilaner dose (minimum 20 mg/kg) for both products and non-interference data from the original approval of Credelio Quattro.
Palatability: In the U.S. field study, which included 552 doses administered to 191 dogs, dogs voluntarily consumed 59.8% of Credelio Quattro doses from an empty bowl, on the floor, or when offered by hand, and an additional 28.4% of doses when offered with food. The administration of 11.8% of doses required placement of the chewable tablet in the back of the dog’s mouth. All doses were administered within 30 minutes of a meal.