A Randomized, Single-Ascending-Dose, Ivermectin-Controlled, Double-Blind Study of Moxidectin in Onchocerca volvulus Infection

PLoS Neglected Tropical Diseases

Volumn 8, Issue 6, 2014, Pages

  Awadzi, Kwablah ^a   Opoku, Nicholas O ^a   Attah, Simon K ^a,b   Lazdins Helds, Janis ^c   Kuesel, Annette C ^c  

^a Onchocerciasis Chemotherapy Research Centre   (Ghana)

^b UNIVERSITY OF GHANA   (Ghana)

^c WORLD HEALTH ORGANIZATION   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

IVERMECTIN; MOXIDECTIN; ANTHELMINTIC AGENT; MACROLIDE; MILBEMYCIN;

ADOLESCENT; ADULT; ARTICLE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; FOLLOW UP; GHANA; HISTOLOGY; HUMAN; HUMAN TISSUE; MAJOR CLINICAL STUDY; MALE; MEAN ARTERIAL PRESSURE; MICROFILARIA (NEMATODE LARVA); ONCHOCERCA VOLVULUS; ONCHOCERCIASIS; ORTHOSTATIC HYPOTENSION; OUTCOME ASSESSMENT; PRURITUS; PULSE RATE; RANDOMIZED CONTROLLED TRIAL; RASH; SIMULIUM; SINGLE DRUG DOSE; VISUAL ACUITY; ANIMAL; BLOOD PRESSURE; CHEMICALLY INDUCED; DRUG EFFECTS; MICROFILARIA; MIDDLE AGED; PARASITOLOGY; SKIN; YOUNG ADULT;

ADOLESCENT; ADULT; ANIMALS; ANTHELMINTICS; BLOOD PRESSURE; DOUBLE-BLIND METHOD; EXANTHEMA; FEMALE; GHANA; HUMANS; IVERMECTIN; MACROLIDES; MALE; MICROFILARIA; MIDDLE AGED; ONCHOCERCA VOLVULUS; ONCHOCERCIASIS; PRURITUS; SKIN; YOUNG ADULT;

EID: 84903471480     PISSN: 19352727     EISSN: 19352735     Source Type: Journal    
DOI: 10.1371/journal.pntd.0002953     Document Type: Article

References (73)

1. African Programme for Onchocerciasis Control (APOC) (2005) Final Communiqué of the 11th session of the Joint Action Forum (JAF) of APOC. WHO. Available: http://www.who.int/apoc/about/structure/jaf/jaf11_final_communique.pdf.
2. Noma M, Nwoke BE, Nutall I, Tambala PA, Enyong P, et al. (2002) Rapid epidemiological mapping of onchocerciasis (REMO): its application by the African Programme for Onchocerciasis Control (APOC). Ann Trop Med Parasitol 96 Suppl 1: S29-S39.
3. Amazigo U, Boatin B, (2006) The future of onchocerciasis control in Africa. Lancet 368: 1946-1947.
4. Dadzie Y, Neira M, Hopkins D, (2003) Final report of the Conference on the eradicability of Onchocerciasis. Filaria J 2: 2.
5. Awadzi K, Opoku NO, Attah SK, Addy ET, Duke BO, et al. (1997) The safety and efficacy of amocarzine in African onchocerciasis and the influence of ivermectin on the clinical and parasitological response to treatment. Ann Trop Med Parasitol 91: 281-296.
6. Awadzi K, Attah SK, Addy ET, Opoku NO, Quartey BT, (1999) The effects of high-dose ivermectin regimens on Onchocerca volvulus in onchocerciasis patients. Trans R Soc Trop Med Hyg 93: 189-194.
7. Awadzi K, Edwards G, Duke BO, Opoku NO, Attah SK, et al. (2003) The co-administration of ivermectin and albendazole-safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol 97: 165-178.
8. Diawara L, Traore MO, Badji A, Bissan Y, Doumbia K, et al. (2009) Feasibility of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: first evidence from studies in mali and senegal. PLoS Negl Trop Dis 3: e497.
9. Traore MO, Sarr MD, Badji A, Bissan Y, Diawara L, et al. (2012) Proof-of-principle of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: final results of a study in Mali and Senegal. PLoS Negl Trop Dis 6: e1825 10.1371/journal.pntd.0001825 [doi];PNTD-D-12-00660 [pii].
10. Tekle AH, Elhassan E, Isiyaku S, Amazigo UV, Bush S, et al. (2012) Impact of long-term treatment of onchocerciasis with ivermectin in Kaduna State, Nigeria: first evidence of the potential for elimination in the operational area of the African Programme for Onchocerciasis Control. Parasit Vectors 5: 28 1756-3305-5-28 [pii];10.1186/1756-3305-5-28 [doi].
11. Duerr HP, Dietz K, Eichner M, (2005) Determinants of the eradicability of filarial infections: a conceptual approach. Trends Parasitol 21: 88-96.
12. Duerr HP, Raddatz G, Eichner M, (2011) Control of onchocerciasis in Africa: threshold shifts, breakpoints and rules for elimination. Int J Parasitol 41: 581-589 S0020-7519(11)00025-7 [pii];10.1016/j.ijpara.2010.12.009 [doi].
13. Duerr HP, Eichner M, (2010) Epidemiology and control of onchocerciasis: the threshold biting rate of savannah onchocerciasis in Africa. Int J Parasitol 40: 641-650 S0020-7519(09)00408-1 [pii];10.1016/j.ijpara.2009.10.016 [doi].
14. Prichard R, Menez C, Lespine A, (2012) Moxidectin and the avermectins: Consanguinity but not identity. Int J Parasitol Drugs Drug Resist 2: 134-153.
15. Monahan CM, Chapman MR, French DD, Klei TR, (1995) Efficacy of moxidectin oral gel against Onchocerca cervicalis microfilariae. J Parasitol 81: 117-118.
16. Tagboto SK, Townson S, (1996) Onchocerca volvulus and O. lienalis: the microfilaricidal activity of moxidectin compared with that of ivermectin in vitro and in vivo. Ann Trop Med Parasitol 90: 497-505.
17. Mancebo OA, Verdi JH, Bulman GM, (1997) Comparative efficacy of moxidectin 2% equine oral gel and ivermectin 2% equine oral paste against Onchocerca cervicalis (Railliet and Henry, 1910) microfilariae in horses with naturally acquired infections in Formosa (Argentina). Vet Parasitol 73: 243-248.
18. Trees AJ, Graham SP, Renz A, Bianco AE, Tanya V, (2000) Onchocerca ochengi infections in cattle as a model for human onchocerciasis: recent developments. Parasitology 120 Suppl: S133-S142.
19. Wyeth Research (2004 April) Investigator's Brochure, Moxidectin, April 2004 (Annex 2 Meeting documents, 2.a of UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (2008) Report on an informal meeting assessing the feasibility of initiating the first Phase 2 study of moxidectin tablets in subjects infected with Onchocerca volvulus.). http://www.who.int/tdr/publications/tdr-research-publications/moxidectin/en/.
20. Geary TG, Mackenzie CD, (2011) Progress and challenges in the discovery of macrofilaricidal drugs. Expert Rev Anti Infect Ther 9: 681-695.
21. Cotreau MM, Warren S, Ryan JL, Fleckenstein L, Vanapalli SR, et al. (2003) The antiparasitic moxidectin: safety, tolerability, and pharmacokinetics in humans. J Clin Pharmacol 43: 1108-1115 10.1177/0091270003257456 [doi];43/10/1108 [pii].
22. Korth-Bradley JM, Parks V, Chalon S, Gourley I, Matschke K, et al. (2011) Excretion of moxidectin into breast milk and pharmacokinetics in healthy lactating women. Antimicrob Agents Chemother 55: 5200-5204 AAC.00311-11 [pii];10.1128/AAC.00311-11 [doi].
23. Korth-Bradley JM, Parks V, Chalon S, Gourley I, Matschke K, et al. (2012) The effect of a high-fat breakfast on the pharmacokinetics of moxidectin in healthy male subjects: a randomized phase I trial. Am J Trop Med Hyg 86: 122-125 86/1/122 [pii];10.4269/ajtmh.2012.11-0415 [doi].
24. Korth-Bradley JM, Parks V, Patat A, Matschke K, Mayer P, et al. (2013) Relative bioavailability of liquid and tablet formulations of the antiparasitic moxidectin. Clinical Pharmacology in Drug Development 1: 32-37.
25. Korth-Bradley JM, Parks V, Wagner F, Chalon S, Gourley I, et al. (2014) Effect of moxidectin on CYP3A4 activity as evaluated by oral midazolam pharmacokinetics in healthy subjects. Clinical Pharmacology in Drug Development 3: 151-157.
26. UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (2008) Report on an informal meeting assessing the feasibility of initiating the first Phase 2 study of moxidectin tablets in subjects infected with Onchocerca volvulus. Geneva: http://www.who.int/tdr/publications/tdr-research-publications/moxidectin/en/.
27. Bryceson AD, Warrell DA, Pope HM, (1977) Dangerous reactions to treatment of onchocerciasis with diethylcarbamazine. Br Med J 1: 742-744.
28. Rougemont A, Boisson ME, Borges da SG, Zander N, (1976) Un essai de traitement collectif par la diéthylcarbamazine dans un village d'hyperendémie onchocerquienne de la région de Bamako (Mali) [Attempt at a collective treatment with diethylcarbamazine in a village in the region of Bamako (Mali) where onchocerciasis is hyperendemic]. Bull World Health Organ 54: 403-410.
29. Fuglsang H, Anderson J, (1974) Letter: Collapse during treatment of onchocerciasis with diethylcarbamazine. Trans R Soc Trop Med Hyg 68: 72-73.
30. Awadzi K, Gilles HM, (1992) Diethylcarbamazine in the treatment of patients with onchocerciasis. Br J Clin Pharmacol 34: 281-288.
31. Francis H, Awadzi K, Ottesen EA, (1985) The Mazzotti reaction following treatment of onchocerciasis with diethylcarbamazine: clinical severity as a function of infection intensity. Am J Trop Med Hyg 34: 529-536.
32. Anderson J, Fuglsang H, de C Marshall T, (1976) Effects of diethylcarbamazine on ocular onchocerciasis. Tropenmed Parasitol 27: 263-278.
33. Post RJ, Cheke RA, Boakye DA, Wilson MD, Osei-Atweneboana MY, et al. (2013) Stability and change in the distribution of cytospecies of the Simulium damnosum complex (Diptera: Simuliidae) in southern Ghana from 1971 to 2011. Parasit Vectors 6: 205 1756-3305-6-205 [pii];10.1186/1756-3305-6-205 [doi].
34. ICH (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) (1996) Guideline for Good Clinical Practice, E6, R1, 1996. www.ich.org.
35. Awadzi K, (1980) The chemotherapy of onchocerciasis II. Quantitation of the clinical reaction to microfilaricides. Ann Trop Med Parasitol 74: 189-197.
36. Hero M, Bird AC, Awadzi K, (1992) Quantification of the ocular reactions to microfilaricides in the chemotherapy of onchocerciasis. Eye 6 (Pt 1):: 93-96.
37. Cancer Therapy Evaluation Program (1999) Common Toxicity Criteria, Version 2.0, DCTD, NCI, DHHS, April 1999. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.
38. Buttner DW, Albiez EJ, von EJ, Erichsen J, (1988) Histological examination of adult Onchocerca volvulus and comparison with the collagenase technique. Trop Med Parasitol 39 Suppl 4: 390-417.
39. Duke BO, Zea-Flores G, Gannon RT, (1990) On the reproductive activity of the female Onchocerca volvulus. Trop Med Parasitol 41: 387-402.
40. Berg, H C. (1983) Random walks in biology. Princeton: Princeton University Press.
41. Awadzi K, Boakye DA, Edwards G, Opoku NO, Attah SK, et al. (2004) An investigation of persistent microfilaridermias despite multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana. Ann Trop Med Parasitol 98: 231-249.
42. Awadzi K, Attah SK, Addy ET, Opoku NO, Quartey BT, et al. (2004) Thirty-month follow-up of sub-optimal responders to multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana. Ann Trop Med Parasitol 98: 359-370.
43. Awadzi K, Dadzie KY, De SG, Remme J, (1990) Reactions to ivermectin treatment in onchocerciasis patients. Acta Leiden 59: 193-199.
44. Basanez MG, Pion SD, Boakes E, Filipe JA, Churcher TS, et al. (2008) Effect of single-dose ivermectin on Onchocerca volvulus: a systematic review and meta-analysis. Lancet Infect Dis 8: 310-322 S1473-3099(08)70099-9 [pii];10.1016/S1473-3099(08)70099-9 [doi].
45. Churcher TS, Pion SD, Osei-Atweneboana MY, Prichard RK, Awadzi K, et al. (2009) Identifying sub-optimal responses to ivermectin in the treatment of River Blindness. Proc Natl Acad Sci U S A 106: 16716-16721 0906176106 [pii];10.1073/pnas.0906176106 [doi].
46. Osei-Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK, (2007) Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two-phase epidemiological study. Lancet 369: 2021-2029.
47. Albiez EJ, Büttner D, Duke BO, (1988) Diagnosis and extirpation of nodules in human onchocerciasis. Trop Med Parasitol 39 Suppl 4: 331-346.
48. Fischer P, Kipp W, Bamuhiga J, Binta-Kahwa J, Kiefer A, et al. (1993) Parasitological and clinical characterization of Simulium neavei-transmitted onchocerciasis in western Uganda. Trop Med Parasitol 44: 311-321.
49. Pion SD, Nana-Djeunga HC, Kamgno J, Tendongfor N, Wanji S, et al. (2013) Dynamics of Onchocerca volvulus Microfilarial Densities after Ivermectin Treatment in an Ivermectin-naive and a Multiply Treated Population from Cameroon. PLoS Negl Trop Dis 7: e2084 10.1371/journal.pntd.0002084 [doi];PNTD-D-11-01182 [pii].
50. Duke BO, (1993) The population dynamics of Onchocerca volvulus in the human host. Trop Med Parasitol 44: 61-68.
51. Duerr HP, Dietz K, Schulz-Key H, Büttner D, Eichner M, (2004) The relationships between the burden of adult parasites, host age and the microfilarial density in human onchocerciasis. Int J Parasitol 34: 463-473 10.1016/j.ijpara.2003.11.008 [doi];S0020751903003308 [pii].
52. Duke BO, Zea-Flores G, Castro J, Cupp EW, Munoz B, (1991) Comparison of the effects of a single dose and of four six-monthly doses of ivermectin on adult Onchocerca volvulus. Am J Trop Med Hyg 45: 132-137.
53. Chavasse DC, Post RJ, Lemoh PA, Whitworth JA, (1992) The effect of repeated doses of ivermectin on adult female Onchocerca volvulus in Sierra Leone. Trop Med Parasitol 43: 256-262.
54. Albiez EJ, Walter G, Kaiser A, Ranque P, Newland HS, White AT, Greene BM, Taylor HR, Buttner DW, (1988) Histological examination of onchocercomata after therapy with ivermectin. Trop Med Parasitol 39: 93-99.
55. Awadzi K, Dadzie KY, Shulz-Key H, Haddock DR, Gilles HM, et al. (1985) The chemotherapy of onchocerciasis X. An assessment of four single dose treatment regimes of MK-933 (ivermectin) in human onchocerciasis. Ann Trop Med Parasitol 79: 63-78.
56. Awadzi K, Dadzie KY, Schulz-Key H, Gilles HM, Fulford AJ, et al. (1986) The chemotherapy of onchocerciasis. XI. A double-blind comparative study of ivermectin, diethylcarbamazine and placebo in human onchocerciasis in northern Ghana. Ann Trop Med Parasitol 80: 433-442.
57. Awadzi K, Dadzie KY, Klager S, Gilles HM, (1989) The chemotherapy of onchocerciasis. XIII. Studies with ivermectin in onchocerciasis patients in northern Ghana, a region with long lasting vector control. Trop Med Parasitol 40: 361-366.
58. Awadzi K, Opoku NO, Addy ET, Quartey BT, (1995) The chemotherapy of onchocerciasis. XIX: The clinical and laboratory tolerance of high dose ivermectin. Trop Med Parasitol 46: 131-137.
59. Awadzi K, (2003) Clinical picture and outcome of Serious Adverse Events in the treatment of Onchocerciasis. Filaria J 2 Suppl 1: S6.
60. Boussinesq M, Richard P, Chippaux JP, (1993) Incidence des éffets secondaires indésirables après une prise d'ivermectine associée à un corticoide administré par voie orale. Bull Soc Fr Parasitol 11: 49-53.
61. Prod'hon J, Boussinesq M, Fobi G, Prud'hom JM, Enyong P, et al. (1991) [Control of onchocerciasis with ivermectin: results of a mass campaign in northern Cameroon]. Bull World Health Organ 69: 443-450.
62. Kamgno J, Gardon J, Gardon-Wendel N, Demanga N, Duke BO, et al. (2004) Adverse systemic reactions to treatment of onchocerciasis with ivermectin at normal and high doses given annually or three-monthly. Trans R Soc Trop Med Hyg 98: 496-504.
63. Kipp W, Bamhuhiiga J, Rubaale T, Buttner DW, (2003) Adverse reactions to ivermectin treatment in Simulium neavei-transmitted onchocerciasis. Am J Trop Med Hyg 69: 621-623.
64. DeSole G, Remme J, Awadzi K, Accorsi S, Alley ES, et al. (1989) Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials. Bull World Health Organ 67: 707-719.
65. African Programme for Onchocerciasis Control (APOC) (2012) Final Communiqué (JAF 17). http://www.who.int/apoc/publications/recommendations/en/index.html.
66. Osei-Atweneboana MY, Eng JK, Boakye DA, Gyapong JO, Prichard RK, (2007) Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two-phase epidemiological study. Lancet 369: 2021-2029.
67. Coffeng LE, Pion SD, O'Hanlon S, Cousens S, Abiose AO, et al. (2013) Onchocerciasis: the pre-control association between prevalence of palpable nodules and skin microfilariae. PLoS Negl Trop Dis 7: e2168 10.1371/journal.pntd.0002168 [doi];PNTD-D-12-00825 [pii].
68. Noordzij M, Dekker FW, Zoccali C, Jager KJ, (2011) Sample size calculations. Nephron Clin Pract 118: c319-c323 000322830 [pii];10.1159/000322830 [doi].
69. Farrokhyar F, Reddy D, Poolman RW, Bhandari M, (2013) Why perform a priori sample size calculation? Can J Surg 56: 207-213 10.1503/cjs.018012 [pii];10.1503/cjs.018012 [doi].
70. Schulz-Key H, Karam M, (1986) Periodic reproduction of Onchocerca volvulus. Parasitology Today 2: 284-286.
71. Büttner D, Albiez EJ, von EJ, Erichsen J, (1988) Histological examination of adult Onchocerca volvulus and comparison with the collagenase technique. Trop Med Parasitol 39 Suppl 4: 390-417.
72. Turner HC, Churcher TS, Walker M, Osei-Atweneboana MY, Prichard RK, et al. (2013) Uncertainty surrounding projections of the long-term impact of ivermectin treatment on human onchocerciasis. PLoS Negl Trop Dis 7: e2169 10.1371/journal.pntd.0002169 [doi];PNTD-D-12-01430 [pii].
73. Mand S, Marfo-Debrekyei Y, Debrah A, Buettner M, Batsa L, et al. (2005) Frequent detection of worm movements in onchocercal nodules by ultrasonography. Filaria J 4: 1.