Abstract
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: Nbib2063659).