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Comparison of the pharmacokinetics (PK) of galeterone novel oral formulations.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Galeterone (gal) is an orally available steroid analog for the treatment of castration resistant prostate cancer (CRPC). A significant food effect, similar to abiraterone, was found when gal, as powder in capsule (PIC), was dosed in a phase I CRPC trial and confirmed in a PK study in human volunteers.The objective of this study was to assess single-dose PK of gal after reformulation and to evaluate effect of food. Methods: In this single-center open-label study, 24 male subjects were assigned to receive once daily doses of between 100 and 3400 mg in either a 3-treatment, 3-period or 4-treatment, 4-period dose scheme. Treatment periods were separated by 7-day washout intervals. Plasma concentrations were measured over 72 hours to assess PK. Two novel tablet formulations were administered in 100 mg doses under fasted and/or fed condition compared to 2600 mg-PIC administered under fed conditions. Escalating doses of PIC (975 to 2600 mg) and tablet (850 to 3400 mg) formulations were evaluated to assess linearity. Results: Gal was well tolerated. Food effect has been negated with the tablet. Exposure from 1700 mg galeterone tablet (fed or fasted) is comparable to a 2,600 mg dose of PIC (fed) (Table). For tablet, AUC(inf) increased in a dose-related and dose-proportional manner from 6,689 ± 2,602 hxng/mL (850 mg) to 20131 ± 9,930 hxng/mL (2,550 mg). Conclusions: The tablet formulation negates the food effect previously observed. Gal may be dosed either fed or fasted with no difference in absorption, which reduces intra-patient variability in exposure. Tablet has more consistent bioavailability and a linear increase in AUC between escalating doses.
100 mg fasted
100 mg fed
1700 mg fed
2600 mg fed
|Cmax (ng/mL)||48.4 ± 24.0 (6)||54.7 ± 28.5 (6)||1,091 ± 400 (5)||1,061 ± 256 (6)|
|Tmax (h)||2.00 (6)
[0.50 – 3.00]
[3.00 – 8.00]
[5.00 – 5.00]
[4.00 – 6.00]
|AUC(inf)||560 ± 254 (5)||690 ± 172 (6)||13,554 ± 6,074 (4)||16,691 ± 5,152 (6)|
*Arithmetic mean ± standard deviation (N) except Tmax for which the median (N) [Range] is reported. **All data from single cross over group except 1700 mg dose.