Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting.

Patients and Methods

Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1:1:1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg.


Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were –0.81 for telotristat ethyl 250 mg (P < .001) and ‒0.69 for telotristat ethyl 500 mg (P < .001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were –0.9, –1.7, and –2.1, respectively. Responses, predefined as a BM frequency reduction ≥ 30% from baseline for ≥ 50% of the double-blind treatment period, were observed in 20%, 44%, and 42% of patients given placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg, respectively. Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 (P < .001). Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl. Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment.


Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid.

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Publication Date


Notes/Citation Information

Published in Journal of Clinical Oncology, v. 35, no. 1, p. 14-23.

© 2016 by American Society of Clinical Oncology

The copyright holder has granted the permission for posting the article here.

Digital Object Identifier (DOI)


Funding Information

We thank Ammy Santiago, Chameleon Communications International (with funding provided by Lexicon Pharmaceuticals), for medical editorial assistance with this manuscript.

Related Content

Clinical trial information: NCT01677910

Appendix: https://doi.org/10.1200/JCO.2016.69.2780

Supplements: https://doi.org/10.1200/JCO.2016.69.2780

Disclosures provided by the authors are available with this article at ascopubs.org/journal/jco.

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