Ectoparasite infestations affect canine and feline populations worldwide and represent major veterinary and public health concerns through their direct pathogenic effects on animals and their role as vectors of numerous pathogens, including zoonotic agents [1]-[3]. Consequently, regular preventive and, when necessary, curative treatments of companion animals are necessary. Veterinarians and expert associations such as the European Scientific Counsel Companion Animal Parasites (ESCCAP) recommend permanent protection during exposure periods, continuous or seasonal for fleas and ticks in most parts of the world [4][5]. Many registered veterinary products are available for treatment and prevention of fleas, and/or ticks but also for mites, lice and flying insects. For registration in Europe, veterinary products must consistently reach a defined threshold of efficacy, i.e. 95% reduction for fleas within 24 h of infestation and 90% reduction for ticks within 48h of infestation, during their claimed efficacy duration [6]. Nevertheless, non-compliance to treatment regimen is a recognized cause of lack of efficacy for ectoparasiticide drugs [7]-[10].

Over the last decade, isoxazolines, a class of ectoparasiticide compounds characterized by a high affinity and antagonism to ligand-gated chloride channels in GABA receptors of arthropods, and by systemic absorption and distribution in the treated companion animal patient, have appeared [11]. These drugs are available in oral, topical, and injectable forms, with efficacy durations for the oral forms of one to three months. A palatable and easy-to-administer oral isoxazoline product with a one-month duration of efficacy is an appropriate solution to maximize compliance and adapt the administration of the product to the dog’s needs, during the flea and tick exposure periods. There are currently four ectoparasiticide isoxazoline formulations for dogs with these characteristics, i.e. NexGard/FrontPro® (afoxolaner), Credelio/AdTab® (lotilaner), Simparica® (sarolaner), and Bravecto® (fluralaner, available in 2 formulations providing either 1-month or 3-month duration of efficacy, without palatability claim, however with “well accepted” label description).

The Committee for Medicinal Products for Veterinary Use (CVMP) of the European Medical Agency (EMA) has produced a Guideline on the demonstration of palatability of veterinary medicinal products [12]. To be considered palatable, an oral product must be voluntarily consumed by at least 80% of dogs. Palatability is an important criterion of choice for an oral product administered repeatedly. It is nevertheless subjective, as granted on the basis of group acceptance of a single product, while individual dogs may react differently following repeated administrations during long periods of time. It is thus helpful for the veterinarian and the dog owner to be informed about any preference dogs may have for any of these products. Paired preference tests are appropriate to provide such answers [13]. A preference test follows a two-option free choice testing design, addressing the question of the preference of one product against the other, while a palatability test is based on acceptance of a single product.

The study presented in this manuscript tested preference between NexGard® and Credelio®. In the EU, NexGard is available as a prescription only medicine (POM) under this name, and as an “over the counter” drug (OTC) under the name of Frontpro®. Similarly, Credelio, a POM product, is available as an OTC drug under the name of AdTab®. For both products, the POM and OTC forms are identical formulations.

Animals were managed similarly and with due regards for their well-being. The study design was reviewed and approved by the sponsor’s (Boehringer Ingelheim Animal Health) and local (BerTek, Inc.) institutional animal care and use committees. The study design and trial facility met the USDA-APHIS animal welfare requirements, and the dogs were housed in individual enclosures of a size in accordance with the Animal Welfare Act.

Consumption of chewable tablets and preferences are summarized in Table 1.

Table 1. Summary of consumption data and preference.

*chi squared test between the afoxolaner and lotilaner groups.

Over the four days of the study, 354 chewable tablets were consumed (88.5%) and there was no consumption in 46 instances (11.5%). When consuming a product, most dogs clearly accepted their first-choice daily offering (consumption of a dropped product following a second offering or consumption of the other product following a drop of a first-choice product rarely occurred). A total amount of 221 (62.4%) afoxolaner chews and 133 (37.6%) lotilaner chews were consumed, making a 1.67 to 1 overall consumption ratio in favor of afoxolaner over lotilaner. On Days 0 and 3, significantly (p < 0.05) more dogs consumed afoxolaner than lotilaner compared to equal consumption (50%), with afoxolaner consumption at 60%, 63%, 57% and 69% of the dogs that consumed a product on Days 0, 1, 2 and 3, respectively (Table 1).

Among the 69 (69%) dogs showing a preference over the entire test period, 53 dogs (76.8%) preferred NexGard, while 16 dogs (23.2%) preferred Credelio (p < 0.0001).

No adverse reactions were reported in any dog, at any time, during the trial.

This study showed that when given a daily choice for four consecutive days to 100 dogs, there was an overall preference for consuming the afoxolaner chewable formulation versus the lotilaner formulation.

Table 2 represents the composition of both formulations. The NexGard formulation is engineered as a flavored “soft chew”. Its main non-active ingredients are corn starch, soy protein fines and other constituents such as glycerol and triglycerides giving a soft treat texture, and a braised artificial additive as flavoring agent [14]. Smaller and denser, Credelio has a more classic tablet-like matrix with compression chemical agents, and a beef additive flavoring agent [15]. These different chemical and physical characteristics may explain the preferences observed in this study for NexGard. Meat based flavors and complex mixtures of flavors seem to be natural preferences in dogs [16]. The study design did not permit isolation of the individual effects of the active ingredient, flavor, texture, tablet size, or excipient matrix, representing a limitation of the study.

Table 2.Qualitative composition (main ingredients) in the afoxolonaner and lotilaner chewable tablets [14][15].

POM = “Prescription-Only Medicine” status; OTC = “Over The Counter” status.

NexGard® has already been tested for preference against Simparica® and Bravecto® and was demonstrated each time the preferred product [17][18]. NexGard Spectra®, an endectoparasiticide oral tablet combining afoxolaner and milbemycin oxime, also formulated in a soft chew almost identically to NexGard, was demonstrated a preferred choice versus Simparica Trio^TM, a palatable chewable tablet for dogs combining sarolaner, moxidectin and pyrantel embonate, and versus Credelio® Plus, a palatable chewable tablet for dogs combining lotilaner and milbemycin oxime [19][20]. These different studies sustain the hypothesis that against other isoxazoline oral formulations, the chewable matrix of afoxolaner oral formulations are usually the preferred option.

Repeated administration needs to be an easy experience for both the dog and its owner to maximize chances of lasting compliance. Considering the importance of the treatment and control of ectoparasiticides in dogs, both for veterinary and public health reasons, and the necessity of repeated administration of ectoparasiticides during the dog’s life, the oral preference of the afoxolaner soft chew is a valuable information for the veterinarian and the dog owner.

The work reported herein was funded by Boehringer Ingelheim Animal Health GA, USA.

All relevant data are provided within the paper.

The study was approved by BerTek Inc. Animal Care and Use Committees (IACUC) with the concurrence of Boehringer Ingelheim.

All authors have reviewed this document and consent to publish the data.

William R. Everett: study protocol, investigation, general supervision. Eric Tielemans: Manuscript drafting.