Telotristat Ethyl Tablets

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Xermelo was studied in a double-blind, placebo-controlled clinical trial of 90 patients with metastatic neuroendocrine tumors and carcinoid syndrome diarrhea. Patients reported between 4 to 12 bowel movements daily despite the use of SSA therapy at a stable dose for at least 3 months [see Clinical Studies]. Placebo or Xermelo 250 mg was administered three times daily for 12 weeks. Concomitant anti-diarrheal medications (e.g., loperamide) were used by 43% (36% and 51% in the placebo and Xermelo group, respectively), pancreatic enzyme replacement medications by 39% (36% and 42% in the placebo and Xermelo group, respectively), and opioid analgesics by 29% (24% and 33% in the placebo and Xermelo group, respectively) of patients during the 12-week double-blind period of the trial.

Table 1 below lists adverse reactions occurring at an incidence of at least 5% in the Xermelo group (N=45) and at an incidence greater than placebo (N=45) during the 12-week placebocontrolled period of the trial.

Table 1: Percent Common Adverse Reactionsa by Treatment Group at 12-Weeks in a Double-Blind Placebo-Controlled Clinical Trial of Patients with Carcinoid Syndrome Diarrhea

In another placebo-controlled clinical trial of patients with carcinoid syndrome diarrhea and less than 4 bowel movements per day, the following additional adverse reactions, not listed in Table 1, of abdominal pain (including upper and lower abdominal pain, abdominal distention and gastrointestinal pain) and constipation were reported in at least 5% of patients in the Xermelo treated group and at an incidence greater than placebo [see WARNINGS AND PRECAUTIONS].

The following is a list of adverse reactions occurring in less than 5% of patients receiving Xermelo during the 12-week placebo-controlled period of the clinical trial:

Investigations: increased alkaline phosphatase, increased alanine aminotransferase, and increased aspartate aminotransferase.

Fecaloma was reported in one patient treated with Xermelo during the 36-week open-label extension period following the 12-week double-blind period of the trial.