Efficacy and Safety of a Single-Dose Mebendazole 500 mg Chewable, Rapidly-Disintegrating Tablet for Ascaris lumbricoides and Trichuris trichiura Infection Treatment in Pediatric Patients: A Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study

Abstract

Abstract.This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of a new chewable, rapidly-disintegrating mebendazole (MBZ) 500 mg tablet for Ascaris lumbricoides and Trichuris trichiura infection treatment. Pediatric patients (1–15 years; N = 295; from Ethiopia and Rwanda) excreting A. lumbricoides and/or T. trichiura eggs were enrolled. The study had a screening phase (3 days), a double-blind treatment phase (DBP, 19 days), and an open-label phase (OLP, 7 days). Patients received MBZ or placebo on day 1 of DBP and open-label MBZ on day 19 ± 2 after stool sample collection. Cure rates (primary endpoint), defined as species-specific egg count of 0 at the end of DBP, were significantly higher in the MBZ group than placebo for A. lumbricoides (83.7% [72/86; 95% CI: 74.2%; 90.8%] versus 11.1% [9/81; 95% CI: 5.2%; 20.1%], P < 0.001) and for T. trichiura (33.9% [42/124; 95% CI: 25.6%; 42.9%] versus 7.6% [9/119; 95% CI: 3.5%; 13.9%], P < 0.001). Egg reduction rates (secondary endpoint) were significantly higher in the MBZ group than placebo for A. lumbricoides (97.9% [95% CI: 94.4; 99.9] versus 19.2% [95% CI: −5.9; 41.5]; P < 0.001) and T. trichiura (59.7% [95% CI: 33.9; 78.8] versus 10.5% [95% CI: −16.8; 32.9]; P = 0.003). Treatment-emergent adverse events (TEAEs) in MBZ group occurred in 6.3% (9/144) of patients during DBP and 2.5% (7/278) during OLP. No deaths, serious TEAEs, or TEAEs leading to discontinuations were reported. A 500 mg chewable MBZ tablet was more efficacious than placebo for the treatment of A. lumbricoides and T. trichiura infections in pediatric patients, and no safety concerns were identified.

Risk of adverse swallowing events and choking during deworming for preschool-aged children

“…Despite these limitations, this evaluation provides a unique “snapshot” of deworming practices in settings where deworming and vitamin A supplementation programs are implemented. Assessments of drug safety for preventive chemotherapy are usually done in carefully-monitored research studies, focusing on pharmacologic reactions and adverse medical events that occur hours or days after administration [ 15 , 29 , 33 ]. In contrast, this evaluation provides information on practices and experiences during deworming in program settings.…”

“…A new disintegrating formulation of mebendazole has been developed by Johnson & Johnson and is underdoing prequalification by WHO [ 33 ]. Preliminary data suggest that this formulation may be ideal for preschool-age children.…”

Commonly Found Zoonotic Parasite Species in Dogs and Cats from a Prominent Pet Market of Dhaka, Bangladesh

“…In dogs, high prevalence were also observed for Toxocara canis A. lumbricoides is the most common intestinal Nematode found in children and adults worldwide. This giant roundworm has lly due to its high prevalence of disease burden in people among Sub Saharan Africa, East Asia and America [18].…”

Toward the 2020 goal of soil-transmitted helminthiasis control and elimination

“…Other factors, such as suboptimal dissolution of the tablets, may further decrease their therapeutic effects [ 36 ]. In addition, PSAC, especially those less than 3 years of age, have difficulty chewing and swallowing the relatively large tablets [ 37 ], and several deaths have been caused by aspiration and choking [ 38 ]. Hence, the Committee welcomes the recent approval of a new, rapidly disintegrating chewable formulation of mebendazole.…”

“…Hence, the Committee welcomes the recent approval of a new, rapidly disintegrating chewable formulation of mebendazole. The drug’s efficacy and tolerability have been shown in a study conducted in Ethiopia and Rwanda [ 37 ], and the drug received approval by the United States Food and Drug Administration (FDA) on October 19, 2016. We now advocate that access to this new formulation be provided in endemic areas, particularly for preventive chemotherapy targeting PSAC.…”