TELESTAR (Telotristat Etiprate for Somatostatin Analogue Refractory Carcinoid Syndrome)

• Change from baseline in stool consistency [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline in the number of cutaneous flushing episodes [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline in abdominal pain [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Change in the frequency of rescue short-acting somatostatin analog [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
• Incidence of treatment-emergent adverse events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

• Change from baseline in stool consistency [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline in the number of cutaneous flushing episodes [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change from baseline in abdominal pain [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Change in the frequency of rescue short-acting somatostatin analog [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Incidence of treatment-emergent adverse events [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

The primary objective of the study is to confirm that at least 1 or more doses of telotristat etiprate compared to placebo is effective in reducing the change from baseline in the number of daily bowel movements (BMs) averaged over the 12-week double-blind portion (Treatment Period) of the trial in patients refractory to current SSA therapy.

• Drug: Telotristat etiprate tablets (250 mg)
  Other Name: LX1606
• Drug: Placebo tablets
  One placebo tablet administered three times daily

• Experimental: 250 mg telotristat etiprate
  One telotristat etiprate (250 mg) tablet administered three times daily
  Intervention: Drug: Telotristat etiprate tablets (250 mg)
• Experimental: 500 mg telotristat etiprate
  Two telotristat etiprate (250 mg) tablets administered three times daily
  Intervention: Drug: Telotristat etiprate tablets (250 mg)
• Placebo Comparator: Placebo
  Placebo administered three times daily
  Intervention: Drug: Placebo tablets

Inclusion Criteria:

• Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor
• Documented history of carcinoid syndrome and currently experiencing ≥4 bowel movements per day during the Run-in period
• Currently receiving stable-dose somatostatin analog (SSA) therapy

• Minimum dose of LAR or depot SSA therapy

  • Octreotide LAR at 30 mg every 4 weeks
  • Lanreotide Depot at 120 mg every 4 weeks
  • Patients who cannot tolerate SSA therapy at a level indicated above will be allowed to enter at their highest tolerated dose
• Ability and willingness to provide written informed consent

Exclusion Criteria:

• Presence of diarrhea attributed to any condition(s) other than carcinoid syndrome
• Karnofsky Performance status ≤60%
• Treatment with any tumor directed therapy, including interferon, chemotherapy, mTOR inhibitors ≤4 weeks prior to Screening, or hepatic embolization, radiotherapy, radiolabelled SSA, and/or tumor debulking ≤12 weeks prior to Screening
• History of short bowel syndrome (SBS)
• Clinically significant cardiac arrhythmia, bradycardia, tachycardia that would compromise patient safety or the outcome of the study, or QTcF >450 ms
• Previous exposure to telotristat etiprate