Cushing's syndrome: levoketoconazole shows benefit in phase 3 trial

  • Fleseriu M & al.
  • Lancet Diabetes Endocrinol
  • 18/09/2019

  • Brian Richardson, PhD
  • Clinical Essentials
L'accesso ai contenuti di questo sito è riservato agli operatori del settore sanitario italiano L'accesso ai contenuti di questo sito è riservato agli operatori del settore sanitario italiano

Takeaway

  • Levoketoconazole (Recorlev) was associated with improvements in mean 24-hour urinary free cortisol (mUFC) and acceptable safety in a phase 3 trial of patients with Cushing's syndrome.

Why this matters

  • Levoketoconazole may represent a useful therapeutic option.

Key results

  • 81% of patients who advanced to the maintenance phase had a complete response (mUFC ≤upper limit of normal) by end-of-dose titration.
  • 31% of patients showed a response at the end of the 6-month maintenance phase.
    • The least-squares mean estimate of the proportion of responders was 0.30 (P=.0154 vs null hypothesis of ≤0.20).
  • Significant mean improvements were observed for:
    • Fasting blood glucose (P<.0001>
    • HbA1c (P<.0001>
    • Total and low-density lipoprotein cholesterol (both P<.0001>
    • Body weight (P<.0001>
    • Acne global score (P=.0063).
    • Hirsutism total score in women (P=.0008).
    • Peripheral edema total score (P=.030).
  • The most common adverse events were nausea (32%) and headache (28%).

Study design

  • 94 patients with Cushing's syndrome were treated with levoketoconazole and analyzed for efficacy and safety outcomes.
  • Funding: Strongbridge Biopharma.

Limitations

  • Small patient sample size.
  • Open-label study.
  • Nonrandomized, single-group study.