TABLET: Relative bioavailability and bioequivalence study of niraparib tablets and capsules in patients with advanced solid tumors.

e17603 Background: Niraparib is a poly (ADP-ribose) polymerase inhibitor, approved as a maintenance treatment (tx) for patients (pts) with advanced ovarian cancer and under investigation in solid tumors, available in 100 mg capsules (starting dose: 200 or 300 mg/day). Compared with capsules, tablets have improved stability in hot and humid conditions. This study assessed the relative bioavailability (BA; Stage 1 [S1]) and bioequivalence (BE; Stage 2 [S2]) between niraparib tablets and capsules. Methods: This was a US, open-label, multicenter, single-cohort, randomized-sequence study with an optional extension phase. Eligible pts were ≥18 years, had histologically/cytologically confirmed advanced solid tumors (metastatic or local), disease progression despite standard therapy (if available), and ECOG performance scores of 0–2. Pts were dosed 1x300 mg tablet or 3x100 mg capsules then crossed over to the other tx after full washout. Pharmacokinetic (PK) parameters were assessed up to 168 hours post-niraparib dose; safety was assessed throughout and for 30 days after last dose (90 days for serious adverse events). A comparison of the log-transformed PK parameters (maximum observed plasma concentration [C max ], area under the plasma concentration–time curve from time 0 to time of the last quantifiable concentration [AUC 0–t ] and from time 0 extrapolated to infinity [AUC 0– ∞ ]) was carried out to evaluate the formulations using a linear mixed-effects model with fixed effects for sequence, period, and tx and random effect for pt nested within sequence. Results: Pts in both stages completed study drug and washout/PK periods and had sufficient PK samples to estimate PK parameters in both periods. In S1 (n=29), a comparable BA performance of both formulations was demonstrated; the 90% confidence intervals (CI) of the geometric least square means (LSM) for C max , AUC 0–t , and AUC 0– ∞ for tablet/capsule were within prespecified 0.80–1.25 limits (intra-pt variability: 12.4–21.9%). An initial 7-day washout period between PK assessments was extended to 14 days in S2 due to significant carryover reported in 6 pts in S1. In S2 (n=108), niraparib PK characteristics were similar following dosing with tablet or capsule (Table); LSM ratios of the key parameters were close to unity and 90% CI for the ratio of C max , AUC 0 –t , and AUC 0 –∞ were within prespecified 0.80–1.25 limits required to demonstrate BE. No new safety signals were reported. Conclusions: Both niraparib formulations were bioequivalent and can be used interchangeably. Editorial support was provided by Fishawack Health, funded by GSK. Clinical trial information: NCT03329001 . [Table: see text]