Guadecitabine is next-generation HMA formulated as a dinucleotide of decitabine and deoxyguanosine delivered as a low volume and pharmaceutically stable subcutaneous (SC) injection. In vivo conversion to active metabolite decitabine results in longer effective half-life and more extended decitabine exposure window than decitabine IV infusion. The differentiated PK profile may lead to improved biological and clinical activity and safety over currently available HMAs (Issa et al. Lancet Oncology 2015).
SGI-110-01 (NCT01261312) was a phase 1-2, dose escalation, multicenter study of subcutaneous regimens of SGI-110 in subjects with intermediate or high-risk myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Several dosing regimens were tested. In regimen 1 and its phase 2 expansion, guadecitabine was administered daily for 5 days of a 28-day cycle. In regimens 2a and 2b, it was administered weekly or twice-weekly, respectively, for 3 weeks of a 28-day cycle. In another part of the phase 2 expansion, it was administered daily for 10 days (1-5 and 8-12) of a 28-day cycle.
The PK data included full concentration-time profiles of parent SGI-110 and its active metabolite, decitabine obtained after the first dose and after dose on day 5 (for regimen 1 and expansion), day 8 (for regimen 2a) or day 12 (for expansion 10-day regimen) of cycle 1.
The abstract reported results of the population PK analysis of data from 98 patients. Since the time the abstract was submitted, more data became available, and the model was updated. This poster describes the population PK modeling of data using an updated dataset from 124 patients.
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2017 ACCP: Population Pharmacokinetics Analysis for Guadecitabine (SGI-110) and Decitabine after Subcutaneous Dosing with SGI-110 in Patients with Relapsed/Refractory AML and MDS