Olaparib does not cause clinically relevant QT/QTc interval prolongation in patients with advanced solid tumours: results from two phase I studies.
Some therapeutic agents in oncology can be causally associated with specific cardiovascular events including QT/QTc interval prolongation. We investigated the effect of multiple dosing of the oral poly (ADP-ribose)-polymerase (PARP) inhibitor, olaparib (tablet formulation) on QT/QTc interval.
Two phase I, open-label, three-part studies (NCT01921140 [study 4] and NCT01900028 [study 7]) were conducted in adults with refractory/resistant advanced solid tumours. In both studies, parts A and B assessed the QT/QTc interval effects of single-dose oral olaparib 100 (study 4) or 300 (study 7) mg and multiple-dose olaparib 300 mg bid for 5 days, respectively, while part C evaluated continued access to olaparib for additional safety analyses. An ANCOVA model tested the primary objective of multiple-dose effects of olaparib on QT interval corrected using Fridericia's formula (QTcF).
Data from 119 and 109 patients were pooled from parts A and B, respectively, for QT/QTc analysis. At pre-dose and up to 12 h post-dose, the upper limits of the 90 % confidence intervals (CIs) for the difference in QTcF least squares means after olaparib multiple dosing versus control (day -1) were CONCLUSION:
Olaparib tablets administered as multiple or single doses had no clinically significant effect on QT/QTc interval.
Full Reference: Swaisland, Helen, Ruth Plummer, Karen So, Sally Garnett, Wendy Bannister, Marc-Antoine Fabre, Corina Dota, and Anitra Fielding. “Olaparib Does Not Cause Clinically Relevant QT/QTc Interval Prolongation in Patients with Advanced Solid Tumours: Results from Two Phase I Studies.” Cancer Chemotherapy and Pharmacology 78, no. 4 (October 2016): 775–84. doi:10.1007/s00280-016-3124-5.
Link to full text: https://www.ncbi.nlm.nih.gov/pubmed/27553432