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Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial

Lookup NU author(s): Dr Petros PerrosORCiD

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Abstract

© 2018 The authors. Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing >4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or >1 symptom or >4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges-Lehmann estimators of median treatment differences from placebo of -54.0% (95% confidence limits, -85.0%, -25.1%, P < 0.001) and -89.7% (95% confidence limits, -113.1%, -63.9%, P < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: NCT02063659).

Publication metadata

Author(s): Pavel M, Gross DJ, Benavent M, Perros P, Srirajaskanthan R, Warner RRP, Kulke MH, Anthony LB, Kunz PL, Horsch D, Weickert MO, Lapuerta P, Jiang W, Kassler-Taub K, Wason S, Fleming R, Fleming D, Garcia-Carbonero R

Publication type: Article

Publication status: Published

Journal: Endocrine-Related Cancer

Year: 2018

Volume: 25

Issue: 3

Pages: 309-322

Print publication date: 01/03/2018

Online publication date: 12/01/2018

Acceptance date: 09/01/2018

Date deposited: 12/03/2018

ISSN (print): 1351-0088

ISSN (electronic): 1479-6821

Publisher: BioScientifica Ltd.

URL: https://doi.org/10.1530/ERC-17-0455

DOI: 10.1530/ERC-17-0455

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