Pharmacokinetic and safety study of co-administration of albendazole, diethylcarbamazine, Ivermectin and azithromycin for the integrated treatment of Neglected Tropical Diseases

Abstract

Background Pharmacokinetic data are a pre-requisite to integrated implementation of large-scale mass drug administration (MDA) for neglected tropical diseases (NTDs). We investigated the safety and drug interactions of a combination of azithromycin (AZI) targeting yaws and trachoma, with the newly approved ivermectin, albendazole, diethylcarbamazine (IDA) regime for Lymphatic Filariasis. Methodology An open-label, randomized, 3-arm pharmacokinetic interaction study in adult volunteers was carried out in Lihir Island, Papua New Guinea. Healthy adult participants were recruited and randomized to (I) IDA alone, (II) IDA combined with AZI, (III) AZI alone. The primary outcome was lack of a clinically relevant drug interaction. The secondary outcome was the overall difference in the proportion of AEs between treatment arms. Results Thirty-seven participants, eighteen men and nineteen women, were randomized and completed the study. There were no significant drug-drug interactions between the study arms. The GMR of Cmax, AUC0–t, and AUC0–∞ for IVM, DEC, ALB-SOX, and AZI were within the range of 80–125% (GMR for AUC0–∞ for IVM, 87.9; DEC, 92.9; ALB-SOX, 100.0; and AZI, 100.1). There was no significant difference in the frequency of AEs across study arms (AZI and IDA alone arms 9/12 (75%), co-administration arm 12/13 (92%); p = 0.44). All AEs were grade 1 and self-limiting. Conclusions Co-administration of AZI with IDA did not show evidence of significant drug-interactions. There were no serious AEs in any of the study arms. Our data support further evaluation of the safety of integrated MDA for NTDs. Clinical Trials Registration. NCT03664063

Mass drug administration of ivermectin, diethylcarbamazine, plus albendazole compared with diethylcarbamazine plus albendazole for reduction of lymphatic filariasis endemicity in Papua New Guinea: a cluster-randomised trial

“…Our findings have important implications for countries that are considering the use of the triple-drug regimen for elimination of lymphatic filariasis. The consistently high efficacy of the triple-drug regimen seen in this study and in other areas of Papua New Guinea 8 , 26 suggests that elimination of lymphatic filariasis is a feasible goal for this country, which has the highest burden of lymphatic filariasis in the South Pacific. 27 Coverage and compliance are key for any mass drug administration programme, and the superior treatment regimen will not fix poor compliance.…”

A simple, high‐throughput and validated LC–MS/MS method for the determination of azithromycin in human plasma and its application to a clinical pharmacokinetic study

“…The AZI used was generic AZI (500 mg tablet) produced by Kern Pharmaceuticals for the study. Volunteers were instructed to fast overnight and were given by direct observation AZI 30 mg/kg (maximum 2 g/dose) in three treatment regimens (John et al, 2020). Serial blood samples were collected at baseline, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h following the dose.…”

Safety of mass drug coadministration with ivermectin, diethylcarbamazine, albendazole, and azithromycin for the integrated treatment of neglected tropical diseases: a cluster randomized community trial

“…We recently reported the results of a clinical study that compared the pharmacokinetics of administration of IDA separately (lymphatic filariasis regimen) or AZI separately (yaws regimen) with coadministration of IDA and AZI (combined treatment regimen). Compared to separately administered treatment, the study demonstrated an absence of clinically relevant drug-drug interactions, and no severe adverse events (AE) were observed [12] . These findings paved the way for more extensive field studies to evaluate the safety of integrated MDA.…”