Phase I single dose, two-period and two-sequence cross-over trial to evaluate the relative bioavailability of two oral pimasertib formulations in advanced cancer patients

D. Mahadevan, Monica Mita, Donald Richards, Edward McClay, Rebecca Suk Heist, A. Kumar, S. Sundararajan, Aung Naing

Producción científica: Articlerevisión exhaustiva

4 Citas (Scopus)

Resumen

Purpose: A phase I two-period two sequence cross-over study compared the bioavailability of two pimasertib (MSC1936369B/AS703026) formulations (capsule versus tablet) in advanced cancer patients. Methods: Patients with advanced solid tumors were randomized to one of two treatment sequences utilizing pimasertib tablet (test; 3 × 20 mg, PO QD) and capsule (standard; 2 × 30 mg, PO QD). The trial comprised a screening and baseline period, two time periods or parts A and B, and a trial extension phase. Results: N = 38 patients were randomized to two treatment sequences S1 and S2. PK parameters t1/2, CL/f, and Vz/f were within the same range for the two formulations. Tablet had bioavailability comparable to capsule based on the analysis of AUC0–t, however, tablet administration resulted in an increase of ~25% in Cmax versus capsule. Common predicted adverse events of pimasertib included ocular events, diarrhea and creatine phosphokinase elevation. Disease control rate was ~29% with 1 partial response and 4 of 10 patients with stable disease >4 months. Conclusions: Pimasertib tablet was overall well tolerated, had a similar safety and efficacy profile to standard capsule formulation and had bioavailability comparable to capsule.

Idioma originalEnglish (US)
Páginas (desde-hasta)681-688
Número de páginas8
PublicaciónCancer chemotherapy and pharmacology
Volumen79
N.º4
DOI
EstadoPublished - abr 1 2017
Publicado de forma externa

ASJC Scopus subject areas

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

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