Exposure-Response Analysis of Sonidegib (LDE225), an Oral Inhibitor of the Hedgehog Signaling Pathway, for Effectiveness and Safety in Patients With Advanced Solid Tumors

• Published in: Journal of clinical pharmacology Vol. 56; no. 11; p. 1406
• Main Authors: Zhou, Jocelyn, Quinlan, Michelle, Hurh, Eunju, Sellami, Dalila
• Format: Journal Article
• Language: English
• Published: England 01.11.2016
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Biphenyl Compounds - administration & dosage; Biphenyl Compounds - adverse effects; Biphenyl Compounds - blood; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Hedgehog Proteins - antagonists & inhibitors; Humans; Male; Middle Aged; Neoplasms - blood; Neoplasms - drug therapy; Pyridines - administration & dosage; Pyridines - adverse effects; Pyridines - blood; Signal Transduction - drug effects; Signal Transduction - physiology; Treatment Outcome; basal cell carcinoma; exposure-response relationship; creatine kinase; sonidegib; tumor response; Hedgehog pathway

Sonidegib selectively inhibits smoothened protein, suppresses the growth of Hedgehog pathway-dependent tumors, and has recently been approved in the indication of locally advanced basal cell carcinoma. A comprehensive exposure-response analysis was conducted to further characterize the relationship...