Chloroquine (CQ) and Azithromycin (AZ) Combination for Malaria Prophylaxis

Summary

This is an open label, Phase 2 study with controlled human malaria infection (CHMI). Twenty three subjects will be enrolled into 2 groups (15 subjects in the Chloroquine-Azithromycin \[CQ/AZ\] Intervention Group, and 8 subjects in the Chloroquine \[CQ\] Group). The CQ/AZ Group will receive experimental intervention of 300 mg of CQ and 2 g of azithromycin (AZ). The CQ Group will receive 300 mg of CQ only. All subjects will participate in the CHMI and will be required to stay at a hotel for evaluation for a maximum of 14 nights starting 7 days after the challenge. A standard dose of atovaquone-proguanil (Malarone®) will be administered to all symptomatic parasitemic subjects under directly observed treatment.

Timeline

Start

2018-09-17

Primary completion

2019-12-30

Completion

2020-01-01

Publications

• Background Heppner DG Jr, Walsh DS, Uthaimongkol N, Tang DB, Tulyayon S, Permpanich B, Wimonwattrawatee T, Chuanak N, Laoboonchai A, Sookto P, Brewer TG, McDaniel P, Eamsila C, Yongvanitchit K, Uhl K, Kyle DE, Keep LW, Miller RE, Wongsrichanalai C. Randomized, controlled, double-blind trial of daily oral azithromycin in adults for the prophylaxis of Plasmodium vivax malaria in Western Thailand. Am J Trop Med Hyg. 2005 Nov;73(5):842-9.
• Background Pereira MR, Henrich PP, Sidhu AB, Johnson D, Hardink J, Van Deusen J, Lin J, Gore K, O'Brien C, Wele M, Djimde A, Chandra R, Fidock DA. In vivo and in vitro antimalarial properties of azithromycin-chloroquine combinations that include the resistance reversal agent amlodipine. Antimicrob Agents Chemother. 2011 Jul;55(7):3115-24. doi: 10.1128/AAC.01566-10. Epub 2011 Apr 4.
• Background Taylor WR, Richie TL, Fryauff DJ, Picarima H, Ohrt C, Tang D, Braitman D, Murphy GS, Widjaja H, Tjitra E, Ganjar A, Jones TR, Basri H, Berman J. Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia. Clin Infect Dis. 1999 Jan;28(1):74-81. doi: 10.1086/515071.
• Background Yeo AE, Rieckmann KH. Increased antimalarial activity of azithromycin during prolonged exposure of Plasmodium falciparum in vitro. Int J Parasitol. 1995 Apr;25(4):531-2. doi: 10.1016/0020-7519(94)00119-9.
• Results Andersen SL, Oloo AJ, Gordon DM, Ragama OB, Aleman GM, Berman JD, Tang DB, Dunne MW, Shanks GD. Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycycline as prophylaxis for malaria in western Kenya. Clin Infect Dis. 1998 Jan;26(1):146-50. doi: 10.1086/516281.
• Results Biswas S. In-vitro antimalarial activity of azithromycin against chloroquine sensitive and chloroquine resistant Plasmodium falciparum. J Postgrad Med. 2001 Oct-Dec;47(4):240-3.
• Results Dunne MW, Singh N, Shukla M, Valecha N, Bhattacharyya PC, Dev V, Patel K, Mohapatra MK, Lakhani J, Benner R, Lele C, Patki K. A multicenter study of azithromycin, alone and in combination with chloroquine, for the treatment of acute uncomplicated Plasmodium falciparum malaria in India. J Infect Dis. 2005 May 15;191(10):1582-8. doi: 10.1086/429343. Epub 2005 Apr 11.
• Results Mzayek F, Deng H, Mather FJ, Wasilevich EC, Liu H, Hadi CM, Chansolme DH, Murphy HA, Melek BH, Tenaglia AN, Mushatt DM, Dreisbach AW, Lertora JJ, Krogstad DJ. Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and chloroquine in healthy volunteers. PLoS Clin Trials. 2007 Jan 5;2(1):e6. doi: 10.1371/journal.pctr.0020006.
• Livezey J, Twomey P, Morrison M, Cicatelli S, Duncan EH, Hamer M, Lee C, Hutter J, Mills K, DeLuca J, Poon L, Selig D, Vuong C, Sousa J, Oliver T, Bennett J, Moon JE, Sikaffy A, Sedegah M, Tosh D, Kreishman-Deitrick M, Waterman P. An open label study of the safety and efficacy of a single dose of weekly chloroquine and azithromycin administered for malaria prophylaxis in healthy adults challenged with 7G8 chloroquine-resistant Plasmodium falciparum in a controlled human malaria infection model. Malar J. 2020 Sep 16;19(1):336. doi: 10.1186/s12936-020-03409-z.

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