Pharmacokinetics & Pharmacodynamics of Diethylcarbamazine (DEC)+ Albendazole (ALB) + Ivermectin (IVE)

Summary

The study will be an open label cohort study with 2 two-treatment groups 2). Both groups will be treated with a single oral administration of Diethylcarbamazine (DEC) 6 mg/kg + Albendazole (ALB) 400 mg + Ivermectin (IVR) 200 µg/kg (IDA). One treatment group will include men and women with W. bancrofti infections (\>50 Mf/ml, N=30). The other treatment group will include men and women who are free of W. bancrofti infection based on negative blood tests for both microfilariae (Mf) and circulating filarial antigen (N=30). Active follow-up for adverse events (AE) will be for 72hrs and passive follow-up for 7 days following treatment. Participants will be followed again at 1 year to evaluate treatment efficacy. Individuals with severe AEs (grade 3 or higher) will be transported to the Agboville District Hospital and cared for by the hospital staff. Based on treatment of over 100 Lymphatic filariasis (LF) infected individuals any AEs develop within the first 72 hours following treatment and uncommonly up to 7 days post-treatment. All individuals will be admitted to a single health center or hospital in Côte d'Ivoire. Subjects will be monitored for 72-hours after treatment for safety and to facilitate sampling for drug analyses and safety tests. Participants will undergo clinical monitoring every 6 hours to evaluate potential adverse effects of Ivermectin + Diethylcarbamazine + Albendazole (IDA) treatment. Participants will also be monitored for hematologic, or biochemical abnormalities during the period of observation.

Timeline

Start

2016-04-17

Primary completion

2016-06

Completion

2016-06-04

Publications

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• Background Awadzi K, Edwards G, Opoku NO, Ardrey AE, Favager S, Addy ET, Attah SK, Yamuah LK, Quartey BT. The safety, tolerability and pharmacokinetics of levamisole alone, levamisole plus ivermectin, and levamisole plus albendazole, and their efficacy against Onchocerca volvulus. Ann Trop Med Parasitol. 2004 Sep;98(6):595-614. doi: 10.1179/000349804225021370.
• Background Bolla S, Boinpally RR, Poondru S, Devaraj R, Jasti BR. Pharmacokinetics of diethylcarbamazine after single oral dose at two different times of day in human subjects. J Clin Pharmacol. 2002 Mar;42(3):327-31. doi: 10.1177/00912700222011247.
• Background Dominguez-Vazquez A, Taylor HR, Greene BM, Ruvalcaba-Macias AM, Rivas-Alcala AR, Murphy RP, Beltran-Hernandez F. Comparison of flubendazole and diethylcarbamazine in treatment of onchocerciasis. Lancet. 1983 Jan 22;1(8317):139-43. doi: 10.1016/s0140-6736(83)92753-8.
• Background El Setouhy M, Ramzy RM, Ahmed ES, Kandil AM, Hussain O, Farid HA, Helmy H, Weil GJ. A randomized clinical trial comparing single- and multi-dose combination therapy with diethylcarbamazine and albendazole for treatment of bancroftian filariasis. Am J Trop Med Hyg. 2004 Feb;70(2):191-6.
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• Background Hooper PJ, Chu BK, Mikhailov A, Ottesen EA, Bradley M. Assessing progress in reducing the at-risk population after 13 years of the global programme to eliminate lymphatic filariasis. PLoS Negl Trop Dis. 2014 Nov 20;8(11):e3333. doi: 10.1371/journal.pntd.0003333. eCollection 2014 Nov.
• Background Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-32. doi: 10.1017/s0031182000007290.
• Background Horton J. Albendazole: a broad spectrum anthelminthic for treatment of individuals and populations. Curr Opin Infect Dis. 2002 Dec;15(6):599-608. doi: 10.1097/00001432-200212000-00008.
• Background Horton J. The development of albendazole for lymphatic filariasis. Ann Trop Med Parasitol. 2009 Oct;103 Suppl 1:S33-40. doi: 10.1179/000349809X12502035776595.
• Background Horton J, Witt C, Ottesen EA, Lazdins JK, Addiss DG, Awadzi K, Beach MJ, Belizario VY, Dunyo SK, Espinel M, Gyapong JO, Hossain M, Ismail MM, Jayakody RL, Lammie PJ, Makunde W, Richard-Lenoble D, Selve B, Shenoy RK, Simonsen PE, Wamae CN, Weerasooriya MV. An analysis of the safety of the single dose, two drug regimens used in programmes to eliminate lymphatic filariasis. Parasitology. 2000;121 Suppl:S147-60. doi: 10.1017/s0031182000007423.
• Alshehri A, Chhonker YS, Bala V, Edi C, Bjerum CM, Koudou BG, John LN, Mitja O, Marks M, King CL, Murry DJ. Population pharmacokinetic model of ivermectin in mass drug administration against lymphatic filariasis. PLoS Negl Trop Dis. 2023 Jun 1;17(6):e0011319. doi: 10.1371/journal.pntd.0011319. eCollection 2023 Jun.
• Bala V, Chhonker YS, Alshehri A, Edi C, Bjerum CM, Koudou BG, King CL, Murry DJ. Population Pharmacokinetics of Diethylcarbamazine in Patients with Lymphatic Filariasis and Healthy Individuals. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0031721. doi: 10.1128/AAC.00317-21. Epub 2021 Jul 26.
• Edi C, Bjerum CM, Ouattara AF, Chhonker YS, Penali LK, Meite A, Koudou BG, Weil GJ, King CL, Murry DJ. Pharmacokinetics, safety, and efficacy of a single co-administered dose of diethylcarbamazine, albendazole and ivermectin in adults with and without Wuchereria bancrofti infection in Cote d'Ivoire. PLoS Negl Trop Dis. 2019 May 20;13(5):e0007325. doi: 10.1371/journal.pntd.0007325. eCollection 2019 May.

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Indications