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Efficacy,Safety,and Dose of Pafuramidine,a New Oral Drug for Treatment of First Stage Sleeping Sickness,in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies
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نویسنده
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burri c. ,yeramian p.d. ,allen j.l. ,merolle a. ,serge k.k. ,mpanya a. ,lutumba p. ,mesu v.k.b.k. ,bilenge c.m.m. ,lubaki j.-p.f. ,mpoto a.m. ,thompson m. ,munungu b.f. ,manuel f. ,josenando t. ,bernhard s.c. ,olson c.a. ,blum j. ,tidwell r.r. ,pohlig g.
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منبع
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plos neglected tropical diseases - 2016 - دوره : 10 - شماره : 2
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چکیده
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Background: sleeping sickness (human african trypanosomiasis [hat]) is caused by protozoan parasites and characterized by a chronic progressive course,which may last up to several years before death. we conducted two phase 2 studies to determine the efficacy and safety of oral pafuramidine in african patients with first stage hat. methods: the phase 2a study was an open-label,non-controlled,proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (bid) for 5 days at two trypanosomiasis reference centers (angola and the democratic republic of the congo [drc]) between august 2001 and november 2004. the phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. the phase 2b study was open-label,parallel-group,controlled,randomized,and conducted at two sites in the drc between april 2003 and february 2007. the phase 2b study was then amended to add an open-label sequence (phase 2b-2),where 30 patients received pafuramidine for 10 days. the primary efficacy endpoint was parasitologic cure at 24 hours (phase 2a) or 3 months (phase 2b) after treatment completion. the primary safety outcome was the rate of occurrence of world health organization toxicity scale grade 3 or higher adverse events. all subjects provided written informed consent. findings/conclusion: pafuramidine for the treatment of first stage hat was comparable in efficacy to pentamidine after 10 days of dosing. the cure rates 3 months post-treatment were 79% in the 5-day pafuramidine,100% in the 7-day pentamidine,and 93% in the 10-day pafuramidine groups. in phase 2b,the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). these results support continuation of the development program for pafuramidine into phase 3. © 2016 burri et al.
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آدرس
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swiss tropical and public health institute,basel,switzerland,university of basel,basel, Switzerland, the vaccine and gene therapy institute of florida,port st. lucie,fl, United States, immtech pharmaceuticals,inc.,vernon hills,il, United States, the qed group,luanda, Angola, médecins sans frontières suisse,genève, Switzerland, lisumbi health centre,kinshasa, Congo, institut national de recherche biomédicale and tropical medicine department,kinshasa university,kinshasa, Congo, programme des maladies tropicales négligées,ministère de la santé publique kinshasa, Congo, ministry of health,kinshasa, Congo, hôspital evangélique de vanga,vanga, Congo, hôspital evangélique de vanga,vanga, Congo, federally qualified community health center,elgin,il, United States, lisumbi health centre,kinshasa, Congo, instituto de combate e de controlo das tripanossomíases,luanda, Angola, instituto de combate e de controlo das tripanossomíases,luanda, Angola, swiss tropical and public health institute,basel,switzerland,university of basel,basel, Switzerland, infectious diseases,global product development,ppd,rockville,md, United States, swiss tropical and public health institute,basel,switzerland,university of basel,basel, Switzerland, university of north carolina,department of pathology and laboratory medicine,school of medicine,chapel hill,nc, United States, swiss tropical and public health institute,basel,switzerland,university of basel,basel, Switzerland
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Authors
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