A phase II dose-increasing study of sitamaquine for the treatment of visceral leishmaniasis in Kenya.
Sitamaquine (WR6026) is an 8-aminoquinoline in development for the oral treatment of visceral leishmaniasis (VL). This was an open-label, dose-increasing study to determine the dose-response and safety profile for sitamaquine in Kenyan patients with VL caused by Leishmania donovani. Patients (mean age 15.9 [range = 5-47] years) received sitamaquine daily for 28 days at one of four doses: 1.75 (n = 12), 2.0 (n = 61), 2.5 (n = 12), or 3.0 (n = 12) mg/kg/day. The primary efficacy outcome was cure (absence of parasites on splenic aspirate) in the intent-to-treat population at day 180. Cure was achieved in 79 (83%) of 95 patients overall, and in 11 (92%) of 12, 49 (80%) of 61, 9 (82%) of 11, and 10 (91%) of 11 patients at sitamaquine doses of 1.75, 2.0, 2.5, or 3.0 mg/kg/day, respectively. The most frequent adverse events during active treatment were abdominal pain (12 [12%] of 97) and headache (11 [11%] of 97), and one patient in each of the 2.5 mg/kg/day and 3.0 mg/kg/day dose groups had a severe renal adverse event. The effects of sitamaquine on the kidney need further investigation. Sitamaquine was efficacious and generally well tolerated in Kenyan patients with VL.
Wasunna
Monique K
MK
Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Rashid
Juma R
JR
Mbui
Jane
J
Kirigi
George
G
Kinoti
Dedan
D
Lodenyo
Hudson
H
Felton
J Mark
JM
Sabin
Antony J
AJ
Albert
M John
MJ
Horton
John
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007630:Kenya; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000634:Aminoquinolines; D000981:Antiprotozoal Agents; C080436:8-aminoquinoline