A phase 1, open-label, drug-drug interaction study of rucaparib with rosuvastatin and oral contraceptives in patients with advanced solid tumors.

Autor: Liao M; Clinical Pharmacology, Clovis Oncology, Inc 5500 Flatrion Pkwy, Boulder, CO, 80301, USA., Jeziorski KG; Department of Gerontology, Public Health and Didactics, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.; Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland.; BioVirtus Research Site Sp. Z.O.O., BioVirtus Medical Centre, Józefów, Poland., Tomaszewska-Kiecana M; BioVirtus Research Site Sp. Z.O.O., BioVirtus Medical Centre, Józefów, Poland., Láng I; Oncology Unit, Istenhegy Private Health Center, Budapest, Hungary., Jasiówka M; Gynecological Oncology Clinic, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Krakow, Poland.; Pleiades Medical Centre, Krakow, Poland., Skarbová V; Department of Internal Medicine and Clinical Pharmacology, Summit Clinical Research, Bratislava, Slovakia., Centkowski P; Department of Oncology and Hematology, Provincial Specialist Hospital, Biala Podlaska, Poland., Ramlau R; Department of Oncology, Poznan University of Medical Sciences, Poznań, Poland., Górnaś M; Department of Chemotherapy, ATTIS Centre, Warsaw, Poland., Lee J; Regulatory Affairs, Clovis Oncology UK, Ltd., Cambridge, UK., Edwards S; Medical Affairs, Clovis Oncology UK, Ltd., Cambridge, UK., Habeck J; Biostatistics, Clovis Oncology, Inc., Boulder, CO, USA., Nash E; Clinical Operations, Clovis Oncology, Inc., Boulder, CO, USA., Grechko N; Clinical Science, Clovis Oncology UK, Ltd., Cambridge, UK., Xiao JJ; Clinical Pharmacology, Clovis Oncology, Inc 5500 Flatrion Pkwy, Boulder, CO, 80301, USA. jxiao@clovisoncology.com.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2021 Nov; Vol. 88 (5), pp. 887-897. Date of Electronic Publication: 2021 Aug 09.
DOI: 10.1007/s00280-021-04338-7
Abstrakt: Purpose: This study aimed at evaluating the effect of rucaparib on the pharmacokinetics of rosuvastatin and oral contraceptives in patients with advanced solid tumors and the safety of rucaparib with and without coadministration of rosuvastatin or oral contraceptives.
Methods: Patients received single doses of oral rosuvastatin 20 mg (Arm A) or oral contraceptives ethinylestradiol 30 µg + levonorgestrel 150 µg (Arm B) on days 1 and 19 and continuous doses of rucaparib 600 mg BID from day 5 to 23. Serial blood samples were collected with and without rucaparib for pharmacokinetic analysis.
Results: Thirty-six patients (n = 18 each arm) were enrolled and received at least 1 dose of study drug. In the drug-drug interaction analysis (n = 15 each arm), the geometric mean ratio (GMR) of maximum concentration (C max ) with and without rucaparib was 1.29 for rosuvastatin, 1.09 for ethinylestradiol, and 1.19 for levonorgestrel. GMR of area under the concentration-time curve from time zero to last quantifiable measurement (AUC 0-last ) was 1.34 for rosuvastatin, 1.43 for ethinylestradiol, and 1.56 for levonorgestrel. There was no increase in frequency of treatment-emergent adverse events (TEAEs) when rucaparib was given with either of the probe drugs. In both arms, most TEAEs were mild in severity and considered unrelated to study treatment.
Conclusion: Rucaparib 600 mg BID weakly increased the plasma exposure to rosuvastatin or oral contraceptives. Rucaparib safety profile when coadministered with rosuvastatin or oral contraceptives was consistent with that of rucaparib monotherapy. Dose adjustments of rosuvastatin and oral contraceptives are not necessary when coadministered with rucaparib. ClinicalTrials.gov NCT03954366; Date of registration May 17, 2019.
(© 2021. The Author(s).)
Databáze: MEDLINE
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