A Phase 3, Randomized, Placebo-controlled, Multicenter, Double-blind Study to Evaluate the Safety and Efficacy of Telotristat Etiprate (LX1606) in Patients with Carcinoid Syndrome

1. Patients >=18 years of age at the time of the Screening visit;2. Patients (males and females) of reproductive potential must agree to use an adequate method of contraception (defined as having a failure rate of less than 1% per year) during the study and for 12 weeks after the follow-up visit. Adequate methods of contraception for patient or partner include condoms with spermicidal gel, diaphragm with spermicidal gel, coil (intrauterine device), surgical sterilization, vasectomy, oral contraceptive pill, depot progesterone injections, progesterone implant, and abstinence during the study and for 12 weeks after the Follow-up
visit. Note: For females, childbearing potential is defined as those who have not undergone surgical sterilization, or those who are not considered postmenopausal. Postmenopause is defined as absence of menstruation for at least 2 years. If necessary, folliclestimulating
hormone (FSH) results >50 IU/L at Screening are confirmatory in the absence of a clear postmenopausal history.;3. Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor (NET) confirmed by CT, MRI or radionuclide imaging;4. Documented history of CS and meeting 1 of the following 2 criteria:;• If currently receiving LAR/Depot/infusion SSA therapy for the treatment of CS, must be currently receiving a stable dose, averaging less than 4 Bowel movements (BMs) per day, and must have >=1 of the following sign/symptoms of CS:
a)Daily stool consistency of type>=5 on Bristol Stool Form Scale (Appendix D in Protocol) for equal or greater than 50% of the days during the Run-in, or
b) Average daily flushing frequency of >=2, or
c) Average daily rating of >=3 for abdominal pain, or
d) Nausea present >=20% of days, or
e) u5-HIAA > ULN;• If not currently receiving SSA therapy, must have >=1 of the following sign/symptoms of CS:
a) Daily stool consistency of type >=5 on Bristol Stool Form Scale (Appendix D of protocol) for equal or greater than 50% of the days during the Run-in, or
b) Average daily flushing frequency of >=2, or
c) Average daily rating of >=3 for abdominal pain, or
d) Nausea present >=20% of days, or
e) u5-HIAA > ULN, or
f) Currently averaging >=4 BMs per day;5. Patient is able and willing to provide written informed consent prior to participation in any study-related

Patients who meet any of the following criteria will be excluded from participating in the study:
1. Presence of diarrhea attributed to any condition(s) other than CS including, but not limited to, fat malabsorption or bile acid malabsorption;2. Presence of >12 watery BMs per day associated with volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome, as judged by the Investigator;3. Positive stool examination for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile at Screening;4. Karnofsky Performance Status <=60% (see Appendix C);5. Clinical laboratory values for hematology (at Screening):
• Absolute neutrophil count (ANC) <=1500 cells/mm3; or
• Platelets <=75,000, cells/mm3; or
• Hemoglobin (Hgb) <=9 g/dL for males and <=8 g/dL for females;6. Hepatic laboratory values (at Screening) such that:
• Asparate transaminase (AST) or alanine aminotransferase (ALT):
a. >=5.5 x ULN if patient has documented history of hepatic metastases,or
b. >=2.5 x ULN if patient does not have documented history of hepatic metastases
• Total bilirubin >1.5 x ULN (unless patient has a ocumented history of
Gilbert's Syndrome); or
• Alkaline phosphatase (ALP) >=5 x ULN, if total bilirubin is >ULN
a. No upper limit on the ALP value if the total bilirubin is <=ULN;7. Serum creatinine >=1.5 x ULN;8. Treatment with any tumor-directed therapy including, but not limited to: interferon, chemotherapy, mTOR inhibitors <4 weeks prior to Screening, or hepatic embolization, radiotherapy, radiolabelled SSA,and/or tumor debulking <12 weeks prior to Screening;9. Major surgery defined as procedures requiring general anesthesia or major regional anesthesia within 8 weeks prior to Screening;10. A history of short bowel syndrome (SBS);11. Current complaints of constipation or history of chronic or idiopathic constipation within 2 years prior to Screening;12. Positive pregnancy test or pregnant or nursing (lactating) (female patients only);13. Life expectancy <12 months from the Screening visit;14. Presence of any clinically significant findings at Screening medical
history, or physical examination (relative to patient population) that, in the Investigator's or Medical Monitor's opinion, would compromise patient safety or the outcome of the study;15. Any other clinically significant laboratory abnormality at Screening that would compromise patient safety or the outcome of the study;16. Clinically significant cardiac arrhythmia, bradycardia, or tachycardia that would compromise patient safety or the outcome of the study;17. A history of substance or alcohol abuse (DSM-IV Criteria for Substance-Related Disorders12) within 2 years prior to Screening;18. Administration of any investigational agent within 30 days of Screening or investigational therapeutic protein or antibody within 90 days prior to Screening;19. Patients who are currently committed to an institution by virtue of an order issued either by judicial or administrative authorities