ECE2014 Oral Communications Pituitary clinical (5 abstracts)
Normalization of urinary cortisol with the potent 11β-hydroxylase inhibitor LCI699 in patients with Cushing's disease: 22-week, multicentre, open-label study
Beverly Biller 1 , Jacques Young 2 , Amir Hamrahian 3 , Maria Fleseriu 4 , Mark Molitch 5 , Rosario Pivonello 6 , Akira Shimatsu 7 , Chikara Shimizu 8 , Tomoaki Tanaka 9 , Tracy White 10 , Annie Hilliard 10 , Chuan Tian 10 , Nicholas Sauter 10 & Xavier Bertagna 11
1Massachusetts General Hospital, Boston, Massachusetts, USA; 2Assistance Publique Hôpitaux de Paris, Paris, France; 3Cleveland Clinic Foundation, Cleveland, Ohio, USA; 4Oregon Health & Science University, Portland, Oregon, USA; 5Northwestern University, Chicago, Illinois, USA; 6Università Federico II di Napoli, Naples, Italy; 7National Hospital Organization Kyoto Medical Center, Kyoto, Japan; 8Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 9Chiba University Hospital, Chiba-city, Chiba, Japan; 10Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 11Hôpital Cochin, Paris, France.
Background: A proof-of-concept study (LINC 1) demonstrated that after 10 weeks, LCI699 normalized UFC in 11/12 patients with Cushing’s disease. This interim analysis of the first eight patients enrolled into a longer-term study (LINC 2) further evaluates LCI699 in Cushing’s disease; the full analysis on all 19 enrolled patients is expected in time for the congress.
Methods: There were two study groups. Previous LINC 1 participants (follow-up cohort (FC)), who were off LCI699 for at least 8 months, were offered re-enrolment if baseline UFC>1×ULN. Twice-daily LCI699 was initiated at the penultimate efficacious/tolerable dose in LINC 1; doses were escalated as needed. Newly enrolled patients (expansion cohort (EC)) had baseline UFC>1.5×ULN. LCI699 was initiated at 2 mg bid (5 mg bid if baseline UFC>3×ULN). Dose was escalated every 2 weeks to 5, 10, 20 and 30 mg bid until UFC was ≤ULN, whereupon that dose was maintained or reduced for safety reasons up to 22 weeks. Main efficacy endpoints were the proportion of responders (UFC≤ULN or ≧50% decrease from baseline) at weeks 10 and 22.
Results: Nineteen patients enrolled (FC, n=4; EC, n=15); eight are included in this interim analysis (FC, n=2; EC, n=6; male:female 3:5; aged 28–51 years); one EC patient discontinued after week 2 for AEs (diarrhoea/muscle weakness/malaise/papule). At week 10, 7/8 patients (87.5%) were responders (FC 2/2; EC 5/6). At week 22, 6/8 patients (75.0%) were responders (FC 1/2; EC 5/6); no responders required a dose increase during weeks 10–22. All responders at both time points had UFC≤ULN. The most common AEs were asthenia (n=5) and nasopharyngitis (n=4). Hypokalaemia developed in four patients. Three patients had ACTH >2×baseline at week 22. One patient experienced a hypocortisolism-related AE. There were no serious AEs.
Conclusions: This interim analysis demonstrates that 22 weeks’ LCI699 treatment reduces UFC≤ULN in 75% of patients, with good tolerability.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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