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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)681-688
Number of pages8
JournalCancer chemotherapy and pharmacology
Volume79
Issue number4
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • Bioavailability
  • Capsule and tablet formulation
  • MEK 1/2 inhibitor
  • Pimasertib

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this