title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Burri
authors.affiliation: The Vaccine and Gene Therapy Institute of Florida, Port St. Lucie, Florida, United States of America.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Yeramian
authors.affiliation: Immtech Pharmaceuticals, Inc., Vernon Hills, Illinois, United States of America.
authors.forename: James L
authors.initials: JL
authors.lastname: Allen
authors.affiliation: The QED group, Luanda, Angola.
authors.forename: Ada
authors.initials: A
authors.lastname: Merolle
authors.affiliation: Médecins sans Frontières Suisse, Genève, Suisse.
authors.forename: Kazadi Kyanza
authors.initials: KK
authors.lastname: Serge
authors.affiliation: Lisumbi Health Centre, Kinshasa, Democratic Republic of the Congo.
authors.forename: Alain
authors.initials: A
authors.lastname: Mpanya
authors.affiliation: Institut National de Recherche Biomédicale and Tropical Medicine Department, Kinshasa University, Kinshasa, Democratic Republic of the Congo.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lutumba
authors.affiliation: Programme des Maladies Tropicales Négligées, Ministère de la Santé Publique Kinshasa, Democratic Republic of the Congo.
authors.forename: Victor Kande Betu Ku
authors.initials: VK
authors.lastname: Mesu
authors.affiliation: Ministry of Health, Kinshasa, Democratic Republic of the Congo.
authors.forename: Constantin Miaka Mia
authors.initials: CM
authors.lastname: Bilenge
authors.affiliation: Hôspital Evangélique de Vanga, Vanga, Democratic Republic of the Congo.
authors.forename: Jean-Pierre Fina
authors.initials: JP
authors.lastname: Lubaki
authors.affiliation: Hôspital Evangélique de Vanga, Vanga, Democratic Republic of the Congo.
authors.forename: Alfred Mpoo
authors.initials: AM
authors.lastname: Mpoto
authors.affiliation: Federally Qualified Community Health Center, Elgin, Illinois, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Lisumbi Health Centre, Kinshasa, Democratic Republic of the Congo.
authors.forename: Blaise Fungula
authors.initials: BF
authors.lastname: Munungu
authors.affiliation: Instituto de Combate e de Controlo das Tripanossomíases, Luanda, Angola.
authors.forename: Francisco
authors.initials: F
authors.lastname: Manuel
authors.affiliation: Instituto de Combate e de Controlo das Tripanossomíases, Luanda, Angola.
authors.forename: Théophilo
authors.initials: T
authors.lastname: Josenando
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Sonja C
authors.initials: SC
authors.lastname: Bernhard
authors.affiliation: Infectious Diseases, Global Product Development, PPD, Rockville, Maryland, United States of America.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Olson
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Blum
authors.affiliation: University of North Carolina, Department of Pathology and Laboratory Medicine, School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Tidwell
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pohlig
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000810:Angola; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001550:Benzamidines / Q000008:administration & dosage* / Q000009:adverse effects*; D015023:Democratic Republic of the Congo / Q000453:epidemiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010419:Pentamidine / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014353:Trypanosomiasis, African / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D001550:Benzamidines; D010419:Pentamidine; C458513:pafuramidine