A multicenter, phase 2 study to evaluate the efficacy and safety of osilodrostat, a new 11β-hydroxylase inhibitor, in japanese patients with endogenous cushing’s syndrome other than cushing’s disease

Tomoaki Tanaka, Fumitoshi Satoh, Makoto Ujihara, Sanae Midorikawa, Tomomi Kaneko, Tamami Takeda, Akina Suzuki, Masahiko Sato, Akira Shimatsu

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1 Citation (Scopus)

Abstract

This phase 2, single-arm, open-label, dose-titration, multicenter study evaluated osilodrostat (11β-hydroxylase inhibitor) in Japanese patients with endogenous Cushing’s syndrome (CS) caused by adrenal tumor/hyperplasia or ectopic adrenocorticotropic hormone syndrome. The primary endpoint was percent change from baseline to week 12 in mean urinary free cortisol (mUFC) at the individual patient level. Of the nine patients enrolled in the study, seven completed the 12-week core treatment period and two discontinued at or prior to week 12 due to adverse events (AEs). Of the seven patients who completed 12 weeks of study treatment, two completed 48 weeks of study treatment. Median osilodrostat exposure was 12 weeks. Median (range) average dose including dose interruption (0 mg/day) was 2.143 (1.16–7.54) mg/day. Median (range, population) percentage change in mUFC was –94.47% (–99.0% to –52.6%, n = 7) at week 12. At week 12, 6/9 patients were complete responders (mUFC ≤ upper limit of normal [ULN]) and 1/9 was a partial responder (mUFC > ULN but decreased by ≥50% from baseline). Most frequent AEs were adrenal insufficiency (n = 7), gamma-glutamyl transferase increase, malaise, and nasopharyngitis (n = 3 each). Serious AEs were seen in four patients. No deaths occurred in this study. In conclusion, osilodrostat treatment led to a reduction in mUFC in all nine patients with endogenous CS other than Cushing’s disease (CD), regardless of disease type, with >80% reduction seen in 6/7 patients at week 12. The safety profile was consistent with previous reports in CD patients, and the reported AEs were manageable.

Original languageEnglish
Article numberEJ19-0617
Pages (from-to)841-852
Number of pages12
Journalendocrine journal
Volume67
Issue number8
DOIs
Publication statusPublished - 2020

Keywords

  • 11β-hydroxylase inhibitor
  • Cushing’s disease
  • Cushing’s syndrome
  • Osilodrostat

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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