Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2014 Apr;99(4):1375-83.
doi: 10.1210/jc.2013-2117. Epub 2013 Dec 11.

LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study

Xavier Bertagna  1 , Rosario Pivonello, Maria Fleseriu, Yiming Zhang, Paul Robinson, Ann Taylor, Catherine E Watson, Mario Maldonado, Amir H Hamrahian, Marco Boscaro, Beverly M K Biller
Affiliations
Clinical Trial

LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study

Xavier Bertagna et al. J Clin Endocrinol Metab. 2014 Apr.

Abstract

Introduction: The clinical features and increased mortality associated with Cushing's syndrome result from a chronic excess of circulating cortisol. As LCI699 potently inhibits 11β-hydroxylase, which catalyzes the final step of cortisol synthesis, it is a potential new treatment for Cushing's disease, the most common cause of endogenous Cushing's syndrome.

Methods: Adult patients with moderate-to-severe Cushing's disease (urinary free cortisol [UFC] levels >1.5 × ULN [upper limit of normal]) received oral LCI699 for 10 weeks in this proof-of-concept study. LCI699 was initiated at 4 mg/d in two equal doses; the dose was escalated every 14 days to 10, 20, 40, and 100 mg/d until UFC normalized, whereupon the dose was maintained until treatment ended (day 70). The primary endpoint was UFC ≤ ULN or a ≥50% decrease from baseline at day 70.

Results: Twelve patients were enrolled and completed the study. Baseline UFC ranged over 1.6-17.0 × ULN. All 12 patients achieved UFC ≤ULN or a ≥50% decrease from baseline at day 70; 11 (92%) had normal UFC levels at that time. After treatment discontinuation (day 84), UFC was >ULN in 10 patients with available measurements. Mean 11-deoxycortisol, 11-deoxycorticosterone, and adrenocorticotropic hormone levels increased during treatment and declined after discontinuation. Mean systolic and diastolic blood pressure decreased from baseline by 10.0 and 6.0 mmHg, respectively. LCI699 was generally well tolerated; most adverse events (AEs) were mild or moderate. The most common AEs included fatigue (7/12), nausea (5/12), and headache (3/12). No serious drug-related AEs were reported.

Conclusions: LCI699 was efficacious and well tolerated in patients with Cushing's disease enrolled in this proof-of-concept study.

Trial registration: ClinicalTrials.gov NCT01331239.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

Associated data