A Phase 1, Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti‐ Wolbachia Candidate Macrofilaricide

Devereux, Graham ORCID: https://orcid.org/0000-0002-0024-4887, Bula, Marcin, Tripp, Karen, Fitzgerald, Richard, Eraut, Nicola, Alam, Muhammad Salman, Moriyama, Tomoyuki, Shinkyo, Raku, Walker, Lauren, Wang, Duolao ORCID: https://orcid.org/0000-0003-2788-2464, Gusovsky, Fabian, van der Velde, Jeannette, Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476, Hong, Weiqian David, O'Neill, Paul M., Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 and Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 (2024) 'A Phase 1, Randomized, Double‐Blind, Placebo‐Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti‐ Wolbachia Candidate Macrofilaricide'. Clinical Pharmacology in Drug Development, Vol 13, Issue 9, pp. 1071-1081.

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Abstract

AWZ1066S has been developed as a potential treatment for the neglected tropical diseases lymphatic filariasis and onchocerciasis. AWZ1066S targets the Wolbachia bacterial endosymbiont present in the causative nematode parasites. This phase 1, first‐in‐human study aimed to assess the safety and pharmacokinetics of AWZ1066S in healthy human participants. In a randomized double‐blind, placebo‐controlled, single ascending dose study, healthy adults received a single oral dose of AWZ1066S (or placebo) and were followed up for 10 days. The planned single doses of AWZ1066S ranged from 100 to 1600 mg, and each dose was administered to a cohort of 8 participants (6 AWZ1066S and 2 placebo). In total 30 people participated, 18 (60%) female, median age 30.0 years (minimum 20, maximum 61). The cohorts administered 100, 200, 300, and 400 mg of AWZ1066S progressed unremarkably. After single 700‐mg doses all 4 participants developed symptoms of acute gastritis and transient increases in liver enzymes. The severity of these adverse events ranged from mild to severe, with 1 participant needing hospital admission. Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis.

Item Type:	Article
Subjects:	QV Pharmacology > QV 38 Drug action. WC Communicable Diseases > Tropical and Parasitic Diseases > WC 680 Tropical diseases (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1002/cpdd.1441
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	11 Jul 2024 10:07
Last Modified:	10 Sep 2024 09:26
URI:	https://archive.lstmed.ac.uk/id/eprint/24821

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