Premium
Dose‐Escalation Study of ICA‐17043 in Patients with Sickle Cell Disease
Author(s) -
Ataga Kenneth I.,
Orringer Eugene P.,
Styles Lori,
Vichinsky Elliott P.,
Swerdlow Paul,
Davis George A.,
DeSimone Philip A.,
Stocker Jonathan W.
Publication year - 2006
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.26.11.1557
Subject(s) - medicine , pharmacokinetics , placebo , dosing , adverse effect , gastroenterology , pathology , alternative medicine
Study Objective . To determine the dose tolerance, safety, and pharmacokinetics of a single oral dose of ICA‐17043 in patients with sickle cell disease. Design . Phase I, randomized, double‐blind, placebo‐controlled, single‐dose, dose‐escalation study. Setting . Four university medical centers. Patients . Twenty‐eight patients with sickle cell disease, aged 18–60 years, who were otherwise healthy and in a noncrisis state. Intervention . Patients in three separate dose cohorts—50 mg, 100 mg, and 150 mg—received single doses of ICA‐17043 or placebo. Measurements and Main Results . The mean area under the concentration‐time curve from time zero extrapolated to infinity (AUC 0–∞ ) for ICA‐17043 increased in a dose‐related manner (11,827, 19,697, and 30,676 ng•hr/ml for 50, 100, and 150 mg, respectively). Overall mean half‐life was 12.8 days. Mean peak plasma concentrations rose between the 50‐ and 100‐mg dose levels but plateaued at 150 mg (59.1, 108.7, and 109.1 ng/ml, respectively). Weekly pharmacokinetic and safety assessments were conducted in each patient during the follow‐up phase for 56 days. No dose‐limiting adverse events were noted in any of the patients. Conclusion . Total systemic exposure of ICA‐17043 after a single oral dose, as measured by AUC 0–∞ , increased nearly proportionally with the dose. The rate of absorption, however, appeared to be delayed at doses greater than 100 mg. With the long half‐life of ICA‐17043 demonstrated in this study, once‐daily dosing is probably adequate to maintain steady‐state plasma concentrations. In addition, single doses of ICA‐17043 were well tolerated.