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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Randomized, Placebo-controlled, Parallel Group, Multicenter, Double-blind Study to Evaluate the Efficacy and Safety of Telotristat Etiprate (LX1606) in Patients With Carcinoid Syndrome Not Adequately Controlled by Somatostatin Analog (SSA) Therapy

Conditions
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Carcinoid Syndrome

Intervention / Treatment
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* Drug: Telotristat etiprate
* Drug: Placebo-matching telotristat etiprate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants were randomized to one of three treatment arms in the double-blind treatment period. After completion of the double-blind treatment period, participants entered an open-label treatment period.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 250 mg Telotristat Etiprate<br>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. | Drug: Telotristat etiprate<br>* Telotristat etiprate tablets.<br>* Other names: LX1606;Drug: Placebo-matching telotristat etiprate<br>* Placebo-matching telotristat etiprate tablets.<br>|
| Experimental: 500 mg Telotristat Etiprate<br>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. | Drug: Telotristat etiprate<br>* Telotristat etiprate tablets.<br>* Other names: LX1606;Drug: Placebo-matching telotristat etiprate<br>* Placebo-matching telotristat etiprate tablets.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo-matching telotristat etiprate<br>* Placebo-matching telotristat etiprate tablets.<br>|
| Experimental: Telotristat Etiprate Open-Label Extension<br>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. | Drug: Telotristat etiprate<br>* Telotristat etiprate tablets.<br>* Other names: LX1606;Drug: Placebo-matching telotristat etiprate<br>* Placebo-matching telotristat etiprate tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 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. | Baseline and 12 Weeks | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period | 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. | 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) | 
| Number of Participants With TEAEs in the Open-Label Extension Period | 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels | 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. | Baseline and Week 12 | 
| Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points | 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. | Baseline and 12 Weeks | 
| Change From Baseline in Abdominal Pain Averaged Across All Time-Points | 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. | Baseline and 12 Weeks |