Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors

John Sarantopoulos, Sanjay Goel, Vincent Chung, Pamela Munster, Shubham Pant, Manish R. Patel, Jeffrey Infante, Hussein Tawbi, Carlos Becerra, Justine Bruce, Fairooz Kabbinavar, Albert Lockhart, Eugene Tan, Shu Yang, Gary Carlson, Jeffrey W. Scott, Sunil Sharma

Research output: Contribution to journalArticle

Abstract

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); Cmax, 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.

Original languageEnglish (US)
Pages (from-to)921-927
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume78
Issue number5
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

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Therapeutic Equivalency
Cross-Over Studies
Tablets
Capsules
Tumors
Pharmacokinetics
Neoplasms
Appointments and Schedules
4-amino-5-fluoro-3-(5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl)quinolin-2(1H)-one
Protein-Tyrosine Kinases
Renal Cell Carcinoma
Nausea
Vomiting
Fatigue
Diarrhea
Cells
Fatigue of materials
Breast Neoplasms
Safety

Keywords

  • Bioequivalence
  • Capsule
  • Dovitinib
  • Pharmacokinetics
  • Tablet
  • TKI258

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors. / Sarantopoulos, John; Goel, Sanjay; Chung, Vincent; Munster, Pamela; Pant, Shubham; Patel, Manish R.; Infante, Jeffrey; Tawbi, Hussein; Becerra, Carlos; Bruce, Justine; Kabbinavar, Fairooz; Lockhart, Albert; Tan, Eugene; Yang, Shu; Carlson, Gary; Scott, Jeffrey W.; Sharma, Sunil.

In: Cancer Chemotherapy and Pharmacology, Vol. 78, No. 5, 01.11.2016, p. 921-927.

Research output: Contribution to journalArticle

Sarantopoulos, J, Goel, S, Chung, V, Munster, P, Pant, S, Patel, MR, Infante, J, Tawbi, H, Becerra, C, Bruce, J, Kabbinavar, F, Lockhart, A, Tan, E, Yang, S, Carlson, G, Scott, JW & Sharma, S 2016, 'Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors', Cancer Chemotherapy and Pharmacology, vol. 78, no. 5, pp. 921-927. https://doi.org/10.1007/s00280-016-3122-7
Sarantopoulos, John ; Goel, Sanjay ; Chung, Vincent ; Munster, Pamela ; Pant, Shubham ; Patel, Manish R. ; Infante, Jeffrey ; Tawbi, Hussein ; Becerra, Carlos ; Bruce, Justine ; Kabbinavar, Fairooz ; Lockhart, Albert ; Tan, Eugene ; Yang, Shu ; Carlson, Gary ; Scott, Jeffrey W. ; Sharma, Sunil. / Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors. In: Cancer Chemotherapy and Pharmacology. 2016 ; Vol. 78, No. 5. pp. 921-927.
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abstract = "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); Cmax, 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.",
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AU - Goel, Sanjay

AU - Chung, Vincent

AU - Munster, Pamela

AU - Pant, Shubham

AU - Patel, Manish R.

AU - Infante, Jeffrey

AU - Tawbi, Hussein

AU - Becerra, Carlos

AU - Bruce, Justine

AU - Kabbinavar, Fairooz

AU - Lockhart, Albert

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