TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome)

Phase 3

Completed

Conditions: Carcinoid Syndrome

Interventions: Drug: Telotristat etiprate
Drug: Placebo-matching telotristat etiprate

Registration Number: NCT01677910

Lead Sponsor: Lexicon Pharmaceuticals

Brief Summary: 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 number of daily bowel movements (BMs) from baseline averaged over the 12-week double-blind portion (Treatment Period) of the trial in patients not adequately controlled by current SSA therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 135

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 long-acting release (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, mechanistic target of rapamycin (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
Previous exposure to telotristat etiprate

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
500 mg Telotristat Etiprate	Telotristat etiprate	Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
250 mg Telotristat Etiprate	Telotristat etiprate	Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Telotristat Etiprate Open-Label Extension	Telotristat etiprate	Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.
500 mg Telotristat Etiprate	Placebo-matching telotristat etiprate	Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Placebo	Placebo-matching telotristat etiprate	Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Telotristat Etiprate Open-Label Extension	Placebo-matching telotristat etiprate	Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.
250 mg Telotristat Etiprate	Placebo-matching telotristat etiprate	Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period	First dose of study drug to within 30 days of last dose of study drug in the Double-Blind Treatment Period (Up to 17.6 Weeks)	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
Number of Participants With TEAEs in the Open-Label Extension Period	First dose of study drug to within 30 days of last dose of study drug in the Open-Label Extension Period (Up to 54.3 Weeks)	An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks	Baseline and 12 Weeks	Participants recorded the number of bowel movements per day in a daily diary. The total number of BMs per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels	Baseline and Week 12	u5-HIAA is a standard test used in clinical practice to assess neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. A negative change from Baseline indicates improvement.
Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points	Baseline and 12 Weeks	Participants recorded the number daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.
Change From Baseline in Abdominal Pain Averaged Across All Time-Points	Baseline and 12 Weeks	Participants recorded abdominal pain in a daily diary. Participants evaluated the level of any abdominal pain using an 11-point numeric rating scale, where: 0=no pain to 10=worst pain ever experienced. The average daily abdominal pain was averaged over the 12-week period. A negative change from Baseline indicates improvement.