Telotristat Etiprate - Expanded Treatment for Patients With Carcinoid Syndrome Symptoms

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the long-term safety and tolerability of orally administered telotristat etiprate.

Official Title
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A Multicenter, Long-term Extension Study to Further Evaluate the Safety and Tolerability of Telotristat Etiprate (LX1606)

Conditions
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Carcinoid Syndrome

Intervention / Treatment
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* Drug: Telotristat etiprate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ongoing participation in a Phase 2 [LX1606.1-202-CS (NCT00853047), LX1606.1-203-CS (NCT01104415)] or Phase 3 [LX1606.1-301-CS (NCT01677910), LX1606.1-303-CS (NCT02063659)] study Patients of childbearing potential must agree to use an adequate method of contraception (defined as having a failure rate of <1% per year) during the study and for 12 weeks after the Follow-up visit. Ability and willingness to provide written informed consent Exclusion Criteria: Major protocol violations or tolerability concerns in a Phase 2 (eg, LX1606.1-202-CS, LX1606.1-203-CS) or Phase 3 (eg, LX1606.1-301-CS, LX1606.1-303-CS) study Positive pregnancy test Presence of any clinically significant findings at entry for medical history, laboratory values, or physical examination

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 250 mg Telotristat Etiprate<br>One telotristat etiprate (250 mg) tablet administered three times daily. | Drug: Telotristat etiprate<br>* Telotristat etiprate tablet (250 mg)<br>* Other names: LX1606;|
| Experimental: 500 mg Telotristat Etiprate<br>Two telotristat etiprate (250 mg) tablets administered three times daily. | Drug: Telotristat etiprate<br>* Telotristat etiprate tablet (250 mg)<br>* Other names: LX1606;|

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) | An adverse event (AE) is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE includes any noxious, pathological, or unintended change in anatomical, physiological, or metabolic functions as indicated by physical signs or symptoms occurring in any phase of the clinical study whether or not considered related to the study medication. A TEAE is an AE that occurs or worsens after receiving study drug. | First dose of study drug (Day 1) up to 15 days post last dose (approximately up to 236 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) Score at Each Visit | QLQ-C30 is a standardized 30-item scale to assess health-related quality of life composed of 5 functional scales (physical functioning [5 items], role functioning [2 items], emotional functioning [4 items], cognitive functioning [2 items], and social functioning [2 items]); 3 symptom scales (fatigue [3 items], nausea/vomiting [2 items], and pain [2 items]); a global health status (GHS) /quality of life (QOL) scale [2 items]; 6 single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties). 28 questions answered:1 (not at all) to 4 (very much) and 2 questions on overall health/QOL answered:1 (poor) to 7 (excellent). All of the scales and single-item measures are transformed to a score:0 to 100. For functioning scales and global QOL higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement). | Baseline, Weeks 24, 48, 72 and 84 | 
| Change From Baseline in Gastrointestinal Symptoms of Carcinoid Neuroendocrine Tumors (GI.NET21) Score at Each Visit | GI.NET21 is a standardized 21-item scale composed of both multi-item scales and single-item measures that include 5 functional scales (gastrointestinal (GI) [5 items], endocrine [3 items], treatment-related [3 items], social functioning [3 items], and disease-related worries scale [DRWS] [3 items]) and 4 single items (muscle and bone pain symptom (BPS), sexual functioning, communication function (CF), body image and information about the disease). Each item is scored from 1 (not at all) to 4 (very much). All of the scales and single-item measures are transformed to a score of 0 to 100. For functioning scales higher scores indicate better functioning (a positive change from Baseline indicates improvement); for symptom scales higher scores indicate more severe symptoms (a negative change from Baseline indicates improvement). | Baseline, Weeks 24, 48, 72 and 84 | 
| Percentage of Participants With Adequate Relief as Per Subjective Global Assessment Question | Participants were asked to respond to the following question: In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain, or discomfort? The percentage of participants reporting adequate relief (answered Yes) were reported. | Baseline, Weeks 12, 24, 36, 48, 60, 72 and 84 | 
| Change From Baseline in Subjective Global Assessment of Carcinoid Syndrome Symptoms on 11-Point Numeric Scale at Each Visit | Participants were asked the following question to assess global symptoms associated with carcinoid syndrome (CS) on an 11-point scale: Rate the severity of your overall carcinoid symptoms over the past 7 days on a scale from 0 to 10, where 0=no symptoms and 10=worst symptoms ever experienced. A negative change from baseline indicated improvement. | Baseline, Weeks 12, 24, 36, 48, 60, 72 and 84 |