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

TY - JOUR

T1 - Telotristat ethyl in carcinoid syndrome

T2 - safety and efficacy in the TELECAST phase 3 trial

AU - Pavel, M.

AU - Benavent, M.

AU - Perros, P.

AU - Srirajaskanthan, R.

AU - Warner, R. R. P.

AU - Kulke, M. H.

AU - Anthony, L. B.

AU - Kunz, P.

AU - Hoersch, D.

AU - Lapuerta, P.

AU - Fleming, R.

AU - Gross, D.

PY - 2018

Y1 - 2018

N2 - 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 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-hour 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).

AB - 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 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-hour 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).

KW - serotonin

KW - safety

U2 - 10.1530/ERC-17-0455

DO - 10.1530/ERC-17-0455

M3 - Article

C2 - 29330194

SN - 1351-0088

VL - 105

SP - 205

EP - 205

JO - ENDOCRINE RELATED CANCER

JF - ENDOCRINE RELATED CANCER

ER -