Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio\xae Plus) for the prevention of heartworm disease (Dirofilaria immitis) in client-owned dogs in the USA

Lisa M Young,Scott Wiseman,Elizabeth Crawley,Kim Wallace,Daniel E Snyder

doi:10.1186/s13071-021-04767-6

Abstract

BackgroundDirofilaria immitis, a globally distributed filarial parasite of dogs, is known to cause serious or fatal cardiopulmonary disease. Client-owned dogs were enrolled in a clinical field study in the USA to evaluate the clinical effectiveness and field safety of an orally administered combination investigational product (IP) containing milbemycin oxime and lotilaner (Credelio® Plus) as compared to a control product (CP) for the prevention of heartworm disease when administered monthly for 11 consecutive months.MethodsIn this 11-month field study, 319 dogs ≥ 8 weeks old confirmed to be heartworm-negative were enrolled from eight geographically distinct US veterinary clinics, including sites in the southern USA and Mississippi River Valley. The dogs were treated with either the IP combination product at 0.75–1.53 mg/kg milbemycin oxime and 20–41.5 mg/kg lotilaner (n = 159) or the CP (Sentinel® Flavor Tabs®; milbemycin oxime/lufenuron) at the label-recommended dose rate (n = 158.) On day 330, effectiveness was evaluated in each dog using antigen and microfilarial (modified Knott’s) testing to assess the establishment of any patent adult heartworm infections.ResultsAll dogs treated with the IP combination product and the CP tested negative (100% prevention) for heartworm infection on day 330. The IP combination product tablets containing milbemycin oxime and lotilaner were well tolerated based on the safety assessments in all treated dogs.ConclusionsThis multi-site clinical study using client-owned dogs demonstrated that monthly use of flavored, chewable tablets containing a combination of milbemycin oxime and lotilaner administered orally under end use conditions is safe for dogs. None of the enrolled dogs developed heartworm infections. Eleven consecutive monthly treatments of the IP provided 100% prevention of heartworm disease caused by D. immitis.Graphical

Highlights

Dirofilaria immitis, a globally distributed filarial parasite of dogs, is known to cause serious or fatal cardiopulmonary disease
The clinic sites were selected in order to provide maximum exposure to HW infections in a real-world setting. This was achieved by enrolling adequate numbers of dogs into each investigational product (IP) and control product (CP) treatment group and by choosing areas of the USA where HW is endemic as demonstrated by prevalence data generated by Companion Animal Parasite Council (CAPC)
Data from all dogs receiving at least one dose of the intended IP or CP were included in the study analysis and results were summarized

Summary

Introduction

Dirofilaria immitis, a globally distributed filarial parasite of dogs, is known to cause serious or fatal cardiopulmonary disease. Heartworm (Dirofilaria immitis), a globally distributed filarial parasite in dogs and other animals, is transmitted by several different mosquito species and is known to cause significant cardiopulmonary disease [1, 2]. Over the last several years there have been reports of lack of effectiveness (LOE) of all approved ML containing drug products that are available as a HW preventive [3, 8,9,10]. The causes of these LOEs are likely multifactorial in nature. Research indicates that prophylactic HW prevention effectiveness may depend on the active ingredient in the formulation, the dose level, and the dosage regimen that is utilized [12]

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Conclusion