113035-132

Comparison of the pharmacokinetics (PK) of galeterone novel oral formulations.

Subcategory: 
Category: 
Genitourinary (Prostate) Cancer
Session Type and Session Title: 
This abstract will not be presented at the 2013 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 
e16075
Citation: 
J Clin Oncol 31, 2013 (suppl; abstr e16075)
Author(s): 
William G. Kramer, Bradley Vince, Carolyn McGarry; Kramer Consulting LLP, North Potomac, MD; Vince and Associates, Overland Park, KS; Tokai Pharmaceuticals Inc., Cambridge, MA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

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.

PK parameters for gal after oral administration of tablet and PIC.
Parameter* Tablet
100 mg fasted
Tablet
100 mg fed
Tablet
1700 mg fed
PIC
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]
5.00 (6)
[3.00 – 8.00]
5.00 (5)
[5.00 – 5.00]
5.00 (6)
[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.