Studies show safety, efficacy of Simparica Trio

June 23, 2020
dvm360 Staff

Three studies evaluate the efficacy and safety of Simparica Trio against canine flea and tick infestations in both laboratory and natural conditions.

Most veterinarians stock their shelves with several parasiticides, which they dole out at two or three per pet. Newly available Simparica Trio (sarolaner-moxidectin-pyrantel—Zoetis) is the first combination drug that shields dogs against fleas, ticks, heartworms and roundworms/hookworms. Simparica Trio has gone through several rounds of testing to evaluate its actions on the targeted parasites.

Sarolaner is an isoxazoline class ectoparasiticide that inhibits the function of the neurotransmitter gamma aminobutyric acid (GABA) and glutamate receptors in insects and arachnids, leading to uncontrolled neuromuscular activity and death in fleas and ticks.1,2 Developed by Zoetis in 2016, sarolaner is sold as Simparica for monthly prevention of fleas and ticks on dogs. The appropriate monthly oral dose for flea and tick control was determined to be 2 mg/kg.3

The newest generation of this drug—Simparica Trio—combines sarolaner with two anthelmintics. The current research assesses Simparica Trio at the approximate minimum label dose: sarolaner 1.2 mg/kg, moxidectin 24 µg/kg and pyrantel pamoate 5 mg/kg. The randomized, masked studies (all conducted by Zoetis) confirm not only the efficacy of this reduced sarolaner dose but also the lack of interference of the two added compounds.

Field study

The first study,4 which looked at both efficacy and safety, was conducted using natural flea infestations in client-owned dogs from 18 veterinary practices in the United States. A total of 422 dogs from 251 households of three or fewer dogs (with at least one dog harboring 10+ fleas) were enrolled.

One dog per household was selected as the primary study subject, with dogs from each household assigned randomly in a 2:1 ratio to receive a chewable tablet of either Simparico Trio (sarolaner 1.2-2.4 mg/kg, moxidectin 24-48 µg/kg, pyrantel pamoate 5-10 mg/kg) or afoxalaner (NexGard—Boehringer Ingelheim) at the label doses. Dogs were dosed at days 0 and 30. Flea counts and examinations for flea allergy dermatitis (FAD) were performed immediately before the initial treatment and again at days 30 and 60. General health was assessed through regular physical examinations, and blood work and urinalyses were conducted prior to initial treatment and at day 60.

Simparica Trio reduced live flea counts, as well as clinical signs of FAD, by 99.0% at day 30 and by 99.7% at day 60. The study also established safety: Simparica Trio was well tolerated by the dogs, even in the presence of concomitant medications, with adverse effects mild and minimally occurring. The flavored, chewable tablets were consumed voluntarily by nine out of 10 dogs, with or without food.

Laboratory studies

The second study, which encompassed five trials,5 evaluated efficacy in a laboratory setting. Dogs were treated with a single oral dose of Simparica Trio at the approximate minimum label dose and infested with 100 unfed, adult fleas (Ctenocephalides felis or C. canis); dosing occurred prior to treatment and weekly for five weeks.

In the first three trials, viable fleas were comb-counted at 24 hours after treatment and after each weekly flea re-infestation. Trial 2 also evaluated drug interference by dividing subjects into sarolaner-alone, moxidectin-alone and pyrantel-alone treatment goups, all at minimum label doses. Trial 4 established speed of kill by incorporating flea counts at three, four, eight and 12 hours after initial treatment and weekly reinfestations. Trial 5 looked at flea reproduction through post-treatment egg collection.

Simparica Trio was 99.7% effective against C. felis and 100% effective against C. canis at 24 hours post treatment and following subsequent re-infestations for at least 35 days. Flea killing ramped up at four hours after treatment, and all treated dogs were flea-free at eight hours. Following weekly re-infestations, the drug reduced fleas by about 98% within 12 hours through day 28. Sarolaner alone showed similar efficacy to Simparica Trio, but both moxidectin and pyrantel used alone produced no difference from placebo at most time points. Simparica Trio produced a complete cessation of egg-laying for 35 days. No adverse events occurred in any of the laboratory-based flea trials.

The final laboratory study6 evaluated the efficacy of Simparica Trio against five hard tick species that commonly infest dogs in the U.S.: Ixodes scapularis, Dermacentor variabilis, Rhipicephalus sanguineus, Amblyomma americanum and Amblyomma maculatum.

A total of 10 trials were performed, using two different strains of each tick species. In each study, 10 dogs were assigned randomly to one of two treatment groups based on prior host-suitability tick counts. The dogs were treated with Simparica Trio at the approximate minimum labeled oral dose on day 0, and then infested with approximately 50 unfed adult ticks on days two, five, 12, 19, 26 and 33. Live tick counts were conducted at 48 hours (72 hours for A. americanum groups) following treatment and after weekly tick re-infestations.

At all time points, dogs treated with Simparica Trio had significantly lower mean live tick counts than placebo-treated dogs, which maintained vital infestations throughout the trials. For I. scapularis, D. variabilis, R. sanguineus and A. maculatum, a single dose of Simparica Trio showed nearly 99% efficacy 48 hours following initial treatment, and over 90% efficacy within 48 hours after all re-infestations through day 28; for one of the two strains of R. sanguineus, there was a slightly lower kill rate (89.7%) on day 14. For A. americanum, the compound was over 99% effective by 72 hours following treatment, and over 98% effective by 72 hours after all re-infestations through day 35. No treatment-related adverse events occurred in any trial.

Data generated by these studies establish that Simparica Trio is thoroughly and rapidly effective, as well as safe, under both experimental and natural conditions, when given monthly at minimum labeled oral doses against the two arthropods for which it was designed. For the flea trials, it also demonstrated efficacy without interference by moxidectin or pyrantel pamoate, and halted reproduction on a sustained monthly basis.

Dr. Capuzzi, who earned her BS and VMD degrees from the University of Pennsylvania, works in small animal practice in the Philadelphia area and is a published author. She has written for The Philadelphia Inquirer, Time, Business Philadelphia, Dog Fancy and Dog World, among others. She is especially interested in public health and animal welfare, and is involved with several organizations whose missions are to improve the lives of domesticated and wild animals.

References

1. McTier TL, Chubb N, Curtis MP, et al. Discovery of sarolaner: A novel, orally administered, broad-spectrum, isoxazoline ectoparasiticide for dogs. Vet Parasitol. 2016;222:3-11.

2. Ozoe Y, Asahi M, Ozoe F, et al. The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels. Biochem Biophys Res Commun. 2010;391(1):744-749.

3. Simparicaproduct information summary. Zoetis US website: zoetisus.com/products/dogs/simparica/pdf/simparica-pi-2016.pdf. Revised June 2019. Accessed June 2020.

4. Kryda K, Mahabir SP, Inskeep T, et al. Safety and efficacy of a novel oral chewable combination tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against natural flea infestations in client-owned dogs in the USA. Parasit Vectors 2020;13(98).

5. Kryda K, Mahabir SP, Carter L, et al. Laboratory studies evaluating the efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) for the treatment and control of flea infestations on dogs. Parasit Vectors. 2020;13(57).

6. Kryda K, Mahabir SP, Chapin S, et al. Efficacy of a novel orally administered combination product containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against induced infestations of five common tick species infesting dogs in the USA. Parasit Vectors. 2020;13(77).