The phase III, placebo-controlled, randomized TELESTAR study evaluated efficacy and safety of telotristat ethyl (TE) in patients (pts) with diarrhea (≥4 bowel movements [BMs]/day) due to carcinoid syndrome (CS) inadequately controlled by somatostatin analogs (SSAs). TE, a tryptophan hydroxylase inhibitor, decreases peripheral serotonin levels. As add-on treatment to SSAs, TE 250 mg 3x/day (tid) and TE 500 mg tid significantly reduced BM frequency (p
Changes from baseline in BM frequency (monitored weekly), urinary 5-hydroxyindoleacetic acid (u5-HIAA; Weeks 18, 24, and 48), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) score (Weeks 24 and 48), and safety during the OLE period were evaluated.
Of the 135 pts randomly assigned, 118 completed the DBT period; 115 pts subsequently entered (and 79 completed) the OLE period. Of the 36 pts who discontinued the OLE period, the most frequent reasons were adverse event (AE; 15 pts) and withdrawal of consent (9 pts). Treatment-emergent AEs led 18 pts to discontinue TE; gastrointestinal disorder was the most commonly reported reason (6 pts). Reductions from baseline in BM frequency (∼2 BMs/day) and u5-HIAA levels (range –20.0 mg to –49.5 mg/24 hours) during the OLE were consistent with results of the DBT period and persisted through Week 48. Improvement in EORTC QLQ-C30 diarrhea subscale scores relative to baseline (range –18.8 to –30.6 points) was notable and persisted through Week 48. Crossover into the OLE period was well tolerated. Treatment-emergent AEs were mainly mild to moderate and occurred at a similar rate as in the DBT period.
Patients benefitted from TE throughout the OLE period. TE was well tolerated over 48 weeks and its efficacy was consistent with previously reported data.
Clinical trial identification
Legal entity responsible for the study
Lexicon Pharmaceuticals, Inc.
Lexicon Pharmaceuticals, Inc.
D. Hörsch: Grants and personal fees from Lexicon Pharmaceuticals, Inc., Ipsen Bioscience, Novartis Pharmaceuticals and Pfizer, Inc. M.H. Kulke: Relationships with Lexicon Pharmaceuticals, Inc., Ipsen Bioscience, and Novartis Pharmaceuticals. M. Caplin: Advisory board, speaker honoraria and/or research funding from Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals and Ipsen Biopharmaceuticals. L. Anthony: Grants from Lexicon Pharmaceuticals, Inc. E. Bergsland: Advisory boards for Ipsen Bioscience, Lexicon Pharmaceuticals, Inc., and Novartis Pharmaceuticals. Research support from Lexicon Pharmaceuticals, Inc., and Novartis Pharmaceuticals. P. Kunz: Research funding Merck & Co., Genetech, Advanced Accelerator Applications, Lexicon Pharmaceuticals, Inc., Oxygen, Esanex, Dicerna Pharmaceuticals, & Ipsen. Advisory boards Novartis Pharmaceuticals, Ipsen, & Lexicon Pharmaceuticals, Inc E. Grande Pulido: Research funding from Astellas, Pfizer and AstraZeneca. J.S. Dillon: Received grants from Lexicon Pharmaceuticals, Inc. P. Lapuerta, P. Banks, S. Jackson: Employee of Lexicon Pharmaceuticals, Inc. M. Pavel: Grants and personal fees from Ipsen Bioscience and Novartis Parhmaceuticals. Personal fees from Lexicon Pharmaceuticals, Inc., and Pfizer, inc. All other authors have declared no conflicts of interest.