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Title:
An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib | Targeted Oncology
Description:
Olaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation. Two stages of sequentially enrolled cohorts: stage 1, pharmacokinetic properties of tablet and capsule formulations were compared in patients with advanced solid tumours; stage 2, tablet dose escalation with expansion cohorts at doses/schedules of interest in patients with solid tumours and BRCAm breast/ovarian cancers. Olaparib 200 mg tablets displayed similar Cmax,ss, but lower AUCss and Cmin,ss than 400 mg capsules. Following multiple dosing, steady-state exposure with tablets ≥300 mg matched or exceeded that of 400 mg capsules. After dose escalation, while 400 mg twice daily was the tablet maximum tolerated dose based on haematological toxicity, 65 % of patients in the randomized expansion phase eventually required dose reduction to 300 mg. Intermittent tablet administration did not significantly improve tolerability. Tumour shrinkage was similar for 300 and 400 mg tablet and 400 mg capsule cohorts. The recommended monotherapy dose of olaparib tablet for Phase III trials was 300 mg twice daily, simplifying drug administration from 16 capsules to four tablets per day. NCT00777582 (ClinicalTrials.gov)
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cancer, article, pubmed, google, scholar, olaparib, cas, astrazeneca, patients, research, ovarian, tablet, brca, study, dose, phase, funding, advanced, clinical, trial, oncol, advisory, oncology, institute, received, board, solid, polymerase, mutations, lancet, attendance, privacy, cookies, content, personal, formulation, inhibitor, drug, tumours, trials, access, nature, polyadpribose, breast, centre, university, publish, search, gourley, ledermann,
Topics {✒️}
/media/press-releases/article/20141218--lynparza-approved gov/drugs/informationondrugs/approveddrugs/ucm427598 recurrent high-grade serous month download article/chapter brcam breast/ovarian cancers triple-negative breast cancer early-phase clinical trials ovarian carcinoma cases /responsibility/code-policies-standards/ simplifying drug administration germ-line brca1/2 mutation population pharmacokinetic meta-analysis recurrent ovarian cancer full article pdf epithelial ovarian cancer ovarian carcinoma tablet dose escalation privacy choices/manage cookies olaparib maintenance therapy advanced breast cancer advanced solid tumours recommended monotherapy dose steady-state exposure phase iii trials parp inhibitor olaparib national research committee investigator-initiated trials clinical trial evaluated medical writing assistance natl cancer inst gynecological cancer intergroup individual participants included wales clinical school brca mutation carriers cancer research uk brca2-deficient tumours tablets ≥300 mg matched cancer therapy intermittent tablet administration scope submit manuscript reduce pill burden check access integrated genomic analyses gene expression profile claire routley phd attended advisory boards ema regulatory submission bristol-myers squibb advisory board attendance advisory board payment
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headline:An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib
description:Olaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation. Two stages of sequentially enrolled cohorts: stage 1, pharmacokinetic properties of tablet and capsule formulations were compared in patients with advanced solid tumours; stage 2, tablet dose escalation with expansion cohorts at doses/schedules of interest in patients with solid tumours and BRCAm breast/ovarian cancers. Olaparib 200 mg tablets displayed similar Cmax,ss, but lower AUCss and Cmin,ss than 400 mg capsules. Following multiple dosing, steady-state exposure with tablets ≥300 mg matched or exceeded that of 400 mg capsules. After dose escalation, while 400 mg twice daily was the tablet maximum tolerated dose based on haematological toxicity, 65 % of patients in the randomized expansion phase eventually required dose reduction to 300 mg. Intermittent tablet administration did not significantly improve tolerability. Tumour shrinkage was similar for 300 and 400 mg tablet and 400 mg capsule cohorts. The recommended monotherapy dose of olaparib tablet for Phase III trials was 300 mg twice daily, simplifying drug administration from 16 capsules to four tablets per day. NCT00777582 (ClinicalTrials.gov)
datePublished:2016-05-12T00:00:00Z
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Maximum Tolerate Dose
Ovarian Cancer Patient
Antitumour Activity
Serous Ovarian Carcinoma
Tablet Dose
Oncology
Biomedicine
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headline:An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib
description:Olaparib is poorly soluble, requiring advanced drug delivery technologies for adequate bioavailability. Sixteen capsules/day are required for the approved 400 mg twice-daily dose; a tablet formulation was developed to reduce pill burden. This clinical trial evaluated the optimal dose and administration schedule of the tablet formulation. Two stages of sequentially enrolled cohorts: stage 1, pharmacokinetic properties of tablet and capsule formulations were compared in patients with advanced solid tumours; stage 2, tablet dose escalation with expansion cohorts at doses/schedules of interest in patients with solid tumours and BRCAm breast/ovarian cancers. Olaparib 200 mg tablets displayed similar Cmax,ss, but lower AUCss and Cmin,ss than 400 mg capsules. Following multiple dosing, steady-state exposure with tablets ≥300 mg matched or exceeded that of 400 mg capsules. After dose escalation, while 400 mg twice daily was the tablet maximum tolerated dose based on haematological toxicity, 65 % of patients in the randomized expansion phase eventually required dose reduction to 300 mg. Intermittent tablet administration did not significantly improve tolerability. Tumour shrinkage was similar for 300 and 400 mg tablet and 400 mg capsule cohorts. The recommended monotherapy dose of olaparib tablet for Phase III trials was 300 mg twice daily, simplifying drug administration from 16 capsules to four tablets per day. NCT00777582 (ClinicalTrials.gov)
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Ovarian Cancer Patient
Antitumour Activity
Serous Ovarian Carcinoma
Tablet Dose
Oncology
Biomedicine
general
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