• Wijith Munasinghe, Sven Stodtmann, Anthony Tolcher, Emiliano Calvo, Michael Gordon, Mathilde Jalving, Judith de Vos-Geelen, Diane Medina, Dennis Bergau, Silpa Nuthalapati, David Hoffman, Stacie Shepherd, and Hao Xiong.
• AbbVie Inc., 1 N Waukegan Rd, North Chicago, IL, United States. wijith.munasinghe@abbvie.com.
• Cancer Chemother. Pharmacol. 2016 Nov 1; 78 (5): 1003-1011.

PurposeVeliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2. This phase 1 study evaluated the effect of veliparib on corrected QT interval using Fridericia's formula (QTcF).MethodsEligible patients with advanced solid tumors received single-dose oral veliparib (200 mg or 400 mg) or placebo in a 6-sequence, 3-period crossover design. The primary endpoint was the difference in the mean baseline-adjusted QTcF between 400 mg veliparib and placebo (∆∆QTcF) at six post-dose time points. Absence of clinically relevant QTcF effect was shown if the 95 % upper confidence bound (UCB) for the mean ∆∆QTcF was <10 ms for all time points. An exposure-response analysis was also performed.ResultsForty-seven patients were enrolled. Maximum mean ∆∆QTcF of veliparib 400 mg was 6.4 ms, with a 95 % UCB of 8.9 ms; for veliparib 200 mg, the maximum mean ∆∆QTcF was 3.6 ms, with a 95 % UCB of 6.1 ms. No patient had a QTcF value >480 ms or change from baseline in QTcF interval >30 ms. Treatment-emergent adverse events (TEAEs) were experienced by 36.2, 48.9, and 47.8 % of patients while receiving veliparib 200 mg, veliparib 400 mg, and placebo, respectively. Most common TEAEs were nausea (12.8 %) and myalgia (8.5 %) after veliparib 200 mg, nausea (8.5 %) and vomiting (8.5 %) after veliparib 400 mg, and nausea (6.5 %) after placebo.ConclusionsSingle-dose veliparib (200 mg or 400 mg) did not result in clinically significant QTc prolongation and was well tolerated in patients with advanced solid tumors.

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