Telotristat Etiprate for Carcinoid Syndrome Therapy

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effect of telotristat etiprate versus placebo on the incidence of treatment-emergent adverse events and on 5-hydroxyindoleacetic acid (5-HIAA) levels.

Official Title
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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

Conditions
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Carcinoid Syndrome

Intervention / Treatment
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* Drug: Telotristat etiprate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years of age All patients of reproductive potential must agree to use an adequate method of contraception during the study and for 12 weeks after the Follow-up visit. Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor Documented history of carcinoid syndrome Patient is able and willing to provide written informed consent prior to participation Exclusion Criteria: Presence of diarrhea attributed to any condition other than carcinoid syndrome. Presence of 12 or more watery bowel movements per day Positive stool examination for enteric pathogens, pathogenic ova or parasites, of Clostridium difficile at Screening Karnofsky Performance Status ≤ 60% Presence of any clinically significant laboratory, medical history, or physical examination findings deemed unacceptable by the Investigator A history of short bowel syndrome History of constipation within 2 years of Screening Life expectancy < 12 months from Screening

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 250 mg Telotristat Etiprate<br>Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period. | Drug: Telotristat etiprate<br>* Telotristat etiprate tablets<br>* Other names: LX1606;Drug: Placebo<br>* Placebo-matching telotristat etiprate tablets<br>|
| Experimental: 500 mg Telotristat Etiprate<br>Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week 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<br>* Placebo-matching telotristat etiprate tablets<br>|
| Placebo Comparator: Placebo<br>Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period. | Drug: Placebo<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 |
| --- | --- | --- |
| 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 17.1 Weeks) | 
| Primary: Percent 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 12 Weeks | 
| Number of Participants With Treatment-Emergent Adverse Events (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 52.6 Weeks) | 

Secondary 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 | 
| Change From Baseline in Stool Form/Consistency Averaged Across All Time-Points | Participants assessed stool form/consistency of a BM using the Bristol Stool Form Scale where: 1=hard lumps to 7=watery liquid. The daily scores were averaged over the 12-week period. A negative change indicates improvement. | Baseline and 12 Weeks | 
| 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 | 
| Change in the Frequency of Rescue Short-acting, Somatostatin Analog (SSA) Used to Treat Carcinoid Syndrome Symptoms Averaged Across All Time-Points | The frequency (the number of times) the participant used rescue with SSA to control symptoms was recorded in a daily diary. The daily number of rescue treatments with SSA was averaged over the 12- week period. A negative change from Baseline (less use of SSA) indicates improvement. | Baseline and 12 weeks | 
| Change From Baseline in the Number of Daily BMs Averaged Over the 12-Week Double-Blind Period, Among Participants Who Were Not Receiving SSA Therapy at Baseline | 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 |