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

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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); 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.

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Acknowledgments

This study was supported by Novartis Pharmaceuticals Corporation. Additional support was provided by the Institute for Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center San Antonio in San Antonio, TX Cancer Center Support Grant P30CA054174. We thank Peter J. Simon, Ph.D., and Amanda L. Kauffman, Ph.D., from ArticulateScience (funded by Novartis Pharmaceuticals Corporation) and Sudipta Ridhurkar from Novartis Healthcare Pvt Ltd for providing medical editorial assistance with this manuscript.

Funding

Funding for this study and editorial assistance for the manuscript was provided by Novartis Pharmaceuticals Corporation.

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Authors and Affiliations

  1. Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, 7979 Wurzbach Road, San Antonio, TX, 78229, USA

    John Sarantopoulos

  2. Montefiore Medical Center, Bronx, NY, USA

    Sanjay Goel

  3. City of Hope National Medical Center, Duarte, CA, USA

    Vincent Chung

  4. University of California, San Francisco, San Francisco, CA, USA

    Pamela Munster

  5. University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA

    Shubham Pant

  6. Florida Cancer Specialists, Sarasota, FL, USA

    Manish R. Patel

  7. Sarah Cannon Research Institute, Nashville, TN, USA

    Manish R. Patel & Jeffrey Infante

  8. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Hussein Tawbi

  9. Baylor Sammons Cancer Center, Dallas, TX, USA

    Carlos Becerra

  10. University of Wisconsin Carbone Cancer Center, Madison, WI, USA

    Justine Bruce

  11. University of California, Los Angeles, Los Angeles, CA, USA

    Fairooz Kabbinavar

  12. Washington University School of Medicine Siteman Cancer Center, St. Louis, MO, USA

    A. Craig Lockhart

  13. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Eugene Tan, Shu Yang, Gary Carlson & Jeffrey W. Scott

  14. University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA

    Sunil Sharma

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  1. John Sarantopoulos
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  2. Sanjay Goel
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  8. Hussein Tawbi
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  9. Carlos Becerra
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  10. Justine Bruce
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  14. Shu Yang
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  15. Gary Carlson
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  16. Jeffrey W. Scott
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  17. Sunil Sharma
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Corresponding author

Correspondence to John Sarantopoulos.

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Sarantopoulos, J., Goel, S., Chung, V. et al. Randomized phase 1 crossover study assessing the bioequivalence of capsule and tablet formulations of dovitinib (TKI258) in patients with advanced solid tumors. Cancer Chemother Pharmacol 78, 921–927 (2016). https://doi.org/10.1007/s00280-016-3122-7

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  • DOI: https://doi.org/10.1007/s00280-016-3122-7

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