Efficacy and Safety of Ascending Dosages of Moxidectin and Moxidectin-albendazole Against Trichuris trichiura in Adolescents: A Randomized Controlled Trial

Abstract

Background Preventive chemotherapy is the main strategy to control soil-transmitted helminth (STH) infections. Albendazole and mebendazole are ubiquitously used, but they are not sufficiently effective against Trichuris trichiura. Moxidectin might be a useful addition to the small drug armamentarium. However, the optimal dosage of moxidectin alone and in combination with albendazole against T. trichiura and other STHs has not yet been determined. Methods A Phase II, randomized, placebo-controlled, dose-finding trial was conducted in 2 secondary schools on Pemba Island, Tanzania. Using a computer-generated list, T. trichiura–infected adolescents were randomly assigned to 7 treatment arms: 8, 16, or 24 mg of moxidectin monotherapy; 8, 16, or 24 mg of moxidectin plus 400 mg of albendazole combination therapy; or placebo. The primary outcome was cure rate (CR) against T. trichiura, analyzed 13 to 20 days after treatment by quadruple Kato-Katz thick smears. Results A total of 290 adolescents were enrolled (41 or 42 per arm). CRs against T. trichiura were 43, 46, and 44% for 8, 16, and 24 mg of moxidectin alone, respectively; 60, 62, and 66% for the same moxidectin dosages plus 400 mg of albendazole, respectively; and 12% for placebo. The moxidectin-albendazole arms also revealed higher CRs and egg reduction rates against hookworm than the monotherapy arms. Moxidectin and its combination with albendazole were well tolerated. Conclusions Moxidectin-albendazole is superior to moxidectin. There is no benefit of using doses above 8 mg, which is the recommended dose for onchocerciasis. The moxidectin-albendazole combination of 8 mg plus 400 mg should be investigated further to develop recommendations for appropriate control of STH infections. Clinical Trials Registration NCT03501251.

Efficacy and safety of moxidectin and albendazole compared to ivermectin and albendazole co-administration in adolescents infected with Trichuris trichiura: a randomized controlled trial protocol

“…We designed a randomized controlled trial to show noninferiority of co-administered moxidectin/albendazole compared to co-administered ivermectin/albendazole in participants aged 12-19 years on Pemba Island, Tanzania. From evidence of previous studies conducted by our research group, we expect similar efficacies from the moxidectin/albendazole combination compared to ivermectin/albendazole 9,10 . Nevertheless, moxidectin might be advantageous in terms of the drug's longer half-life and as an alternative in areas with possible emerging ivermectin resistance 20,22 .…”

“…Few adverse events (AEs) have been reported following albendazole, ivermectin or moxidectin single and co-administration in STH-infected individuals. The most common AEs were abdominal cramps, headache, itching, fatigue, nausea, diarrhea, fever and vertigo [8][9][10]20,[33][34][35] .…”

“…Moxidectin recently got approval by the US Food and Drug Administration (FDA) for the treatment of onchocerciasis at an oral single-dose of 8 mg. Clinical trials carried out by our research group have shown that the combination of moxidectin/albendazole might reveal high potential in the treatment of STH infections 9,10 . Moreover, the FDA-approved 8 mg dose, both in monotherapy and in combination with albendazole, was found to perform equally well as higher doses of moxidectin against STH species, as shown by our recent dose-finding study against T. trichiura infections 10 . It remains to be explored whether the longer half-life of moxidectin (T 1/2 : 491-832 hours) 11,12 compared to ivermectin (T 1/2 :16-32 hours; increasing with age) 13 might prove beneficial to the treatment of STH infections and long-term outcomes 14 .…”

Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

“… 63 Similarly, the alternative drug combination of albendazole and moxidectin is also being explored for the treatment of trichuriasis given that moxidectin is an approved treatment for onchocerciasis. 64 …”

Structural requirements for dihydrobenzoxazepinone anthelmintics: actions against medically important and model parasites -Trichuris muris,Brugia malayi,Heligmosomoides polygyrusandSchistosoma mansoni

“…Indeed, the large-scale efforts to treat lymphatic filariasis have indirectly enhanced the number of people being treated for soil transmitted helminths [56]. Similarly, the alternative drug combination of albendazole and moxidectin is also being explored for the treatment of Trichuriasis given that moxidectin is an approved treatment for onchocerciasis [57].…”