Cancer chemotherapy and pharmacology · 2016
Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors.
Клиническое исследование I фазыСтатьяМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Sarantopoulos John, Goel Sanjay, Chung Vincent, Munster Pamela, Pant Shubham, Patel Manish R, Infante Jeffrey, Tawbi Hussein, Becerra Carlos, Bruce Justine, Kabbinavar Fairooz, Lockhart A Craig, Tan Eugene, Yang Shu, Carlson Gary, Scott Jeffrey W, Sharma Sunil
Аннотация
PURPOSE: A capsule formulation of the tyrosine kinase inhibitor dovitinib (TKI258) was recently studied in a phase 3 renal cell carcinoma trial; however, tablets are the planned commercial formulation. Therefore, this randomized 2-way crossover study evaluated the bioequivalence of dovitinib tablet and capsule formulations in pretreated patients with advanced solid tumors, excluding breast cancer.
METHODS: In this 2-part study, eligible patients received dovitinib 500 mg once daily on a 5-days-on/2-days-off schedule. During the 2-period bioequivalence phase, patients received their initial formulation (capsule or tablet) for 3 weeks before being switched to the alternative formulation in the second period. Patients could continue to receive dovitinib capsules on the same dosing schedule during the post-bioequivalence phase.
RESULTS: A total of 173 patients were enrolled into the bioequivalence phase of the study (capsule → tablet, n = 88; tablet → capsule, n = 85), and 69 patients had evaluable pharmacokinetics (PK) for both periods. PK analyses showed similar exposure and PK profiles for the dovitinib capsule and tablet formulations and supported bioequivalence [geometric mean ratios: AUClast, 0.95 (90 % CI 0.88-1.01); C max, 0.98 (90 % CI 0.91-1.05)]. The most common adverse events, suspected to be study drug related, included diarrhea (60 %), nausea (53 %), fatigue (45 %), and vomiting (43 %). Of 168 patients evaluable for response, 1 achieved a partial response, and stable disease was observed in 32 % of patients.
CONCLUSIONS: Dovitinib capsules and tablets were bioequivalent, with a safety profile similar to that observed in other dovitinib studies of patients with heavily pretreated advanced solid tumors.
METHODS: In this 2-part study, eligible patients received dovitinib 500 mg once daily on a 5-days-on/2-days-off schedule. During the 2-period bioequivalence phase, patients received their initial formulation (capsule or tablet) for 3 weeks before being switched to the alternative formulation in the second period. Patients could continue to receive dovitinib capsules on the same dosing schedule during the post-bioequivalence phase.
RESULTS: A total of 173 patients were enrolled into the bioequivalence phase of the study (capsule → tablet, n = 88; tablet → capsule, n = 85), and 69 patients had evaluable pharmacokinetics (PK) for both periods. PK analyses showed similar exposure and PK profiles for the dovitinib capsule and tablet formulations and supported bioequivalence [geometric mean ratios: AUClast, 0.95 (90 % CI 0.88-1.01); C max, 0.98 (90 % CI 0.91-1.05)]. The most common adverse events, suspected to be study drug related, included diarrhea (60 %), nausea (53 %), fatigue (45 %), and vomiting (43 %). Of 168 patients evaluable for response, 1 achieved a partial response, and stable disease was observed in 32 % of patients.
CONCLUSIONS: Dovitinib capsules and tablets were bioequivalent, with a safety profile similar to that observed in other dovitinib studies of patients with heavily pretreated advanced solid tumors.