Background: Telotristat ethyl (TE) is approved to treat inadequately controlled carcinoid syndrome (CS) diarrhea in combination with somatostatin analog (SSA) therapy. Understanding the time to onset of sustained BM frequency improvement is important when considering the use of TE in patients with CS diarrhea. We present data on time to sustained improvement and worsening in BM frequency during the double-blind treatment (DBT) period of TELECAST, a phase 3, randomized, placebo-controlled, double-blind study in patients with CS that required additional treatment, primarily due to gastrointestinal symptoms. Methods: Stable dose SSA was not required. Patients were treated with TE 250 mg 3 times per day (tid), TE 500 mg tid, or placebo tid. Sustained response was defined as the time from the first double-blind dose date to the first day of 2 consecutive weeks with BM frequency change of at least 30% from baseline. The time to the first sustained response in the TELECAST study was examined among treatment groups and analyzed using Cox regression. Results: There were 26 patients on placebo and 25 patients on either 250 mg or 500 mg telotristat groups. Sustained improvement in BM frequency over the 12-week DBT period was achieved in 6, 16, and 16 patients on placebo, TE 250 mg, and TE 500 mg treatment groups. Median time to sustained ≥ 30% improvement was 4-5 weeks with TE at both dosing levels, with no median reached on placebo. First occurrence of sustained improvements in BM frequency occurred within 4-68 days. Time to sustained worsening was delayed on the 500-mg dose of TE (no percentile reached) and is statistically significant (p = 0.021, HR: 0.25) Conclusions: Treatment with telotristat ethyl may provide sustained BM frequency reduction within 4-5 weeks (median) of initiating therapy. No median was reached on placebo due to fewer patients with sustained improvement. Additionally, TE 500 mg tid may also offer additional clinical benefit by reducing sustained BM worsening. Clinical trial information: NCT02063659