Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies.
Bottom Line: In conclusion, the MTD of OPB-51602 was 6 mg.OPB-51602 was safe and well tolerated in a dose range of 1-4 mg.However, long-term administration at higher doses was difficult with the daily dosing schedule, and no response was seen.
Affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.Show MeSH
Related in: MedlinePlus
Mentions: OPB-51602 was rapidly absorbed after both single and multiple administrations. The median time to reach the maximum plasma concentration (tmax) was between 2.0 and 4.5 h (Table3, Fig.1). For the lower dose groups (the 1- and 2-mg cohorts), terminal-phase elimination half-life (t1/2,z) was evaluable in a few patients due to low OPB-51602 plasma levels after single administration. The mean t1/2,z was 50.1–240.0 h after multiple administrations. Exposure (area under the plasma concentration–time curve from 0 to 24 h [AUC24 h] and maximum plasma drug concentration [Cmax]) tended to increase in a dose-dependent manner following multiple administrations across the dose range from 1 to 4 mg (Table3). We observed accumulation of OPB-51602 with a 2.6–10.2-fold increase in AUC24 h and a 1.4–4.6-fold increase in Cmax with doses of 1, 2, 3, and 4 mg.
Affiliation: Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Nagoya, Japan.