Abstract
Purpose
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.
Results
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.
Conclusion
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.
Document Type
Article
Publication Date
1-1-2017
Digital Object Identifier (DOI)
https://doi.org/10.1200/JCO.2016.69.2780
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.
Repository Citation
Kulke, Matthew H.; Hörsch, Dieter; Caplin, Martyn E.; Anthony, Lowell B.; Bergsland, Emily; Öberg, Kjell; Welin, Staffan; Warner, Richard R. P.; Lombard-Bohas, Catherine; Kunz, Pamela L.; Grande, Enrique; Valle, Juan W.; Fleming, Douglas; Lapuerta, Pablo; Banks, Phillip; Jackson, Shanna; Zambrowicz, Brian; Sands, Arthur T.; and Pavel, Marianne, "Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome" (2017). Internal Medicine Faculty Publications. 134.
https://uknowledge.uky.edu/internalmedicine_facpub/134
Data Supplement
protocol 692780.pdf (297 kB)
Protocol
10.1200-JCO.2016.69.2780FigureA1.pdf (117 kB)
Fig A1.
10.1200-JCO.2016.69.2780TableA1.pdf (422 kB)
Table A1.
10.1200-JCO.2016.69.2780Figure2.pdf (507 kB)
Table A2.
10.1200-JCO.2016.69.2780Figure3.pdf (664 kB)
Table A3.
10.1200-JCO.2016.69.2780Figure4.pdf (376 kB)
Table A4.
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.