Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome

Phase 2

Completed

Conditions: Carcinoid Syndrome

Interventions: Drug: Telotristat etiprate

Registration Number: NCT01104415

Lead Sponsor: Lexicon Pharmaceuticals

Brief Summary: The purpose of the study is to evaluate the safety and tolerability of orally administered telotristat etiprate (LX1606) in participants with symptomatic carcinoid syndrome.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 15

Inclusion Criteria

Males and females, aged 18 and older
Biopsy-proven metastatic carcinoid tumor of the gastrointestinal (GI) tract with disease extent confirmed by computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide imaging
Symptomatic carcinoid syndrome (≥4 bowel movements per day)
Ability to provide written informed consent

Exclusion Criteria

≥ 12 high-volume, watery bowel movements per day
Sponsor-unacceptable clinical laboratory values for hematology and liver function tests at screening
Karnofsky status ≤70% - unable to care for self
Surgery within 60 days prior to screening
A history of short bowel syndrome
Life expectancy < 12 months
History of substance or alcohol abuse within 2 years prior to screening
Administration of any investigational drug within 30 days of screening or any therapeutic protein or antibody within 90 days of screening

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Telotristat etiprate - Core Phase	Telotristat etiprate	Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.
Telotristat etiprate - Extension Period	Telotristat etiprate	Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase	Baseline up to Week 12 in the Core Phase	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. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period	Up to 124 Weeks in the 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. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Number of Bowel Movements (BMs)	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24	Participants recorded the number of bowel movements in a daily diary. The change from baseline value was calculated as the difference between mean numbers of BMs of the post-baseline interval (Weeks 9 to 12) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome	Core Phase: Weeks 9-12; Extension Period: Week 24	Participants assessed their symptoms using a weekly subjective response 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 values for improvement in global assessment of symptoms associated with carcinoid syndrome in the Core Phase were averaged from Weeks 9 to 12.
Change From Baseline in Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24	Sensation/severity of nausea was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of nausea experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Change From Baseline in Percentage of Days With Sensation of Urgency to Defecate	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24	Participants assessed the urgency to defecate using a daily diary response to the following question, "Have you felt or experienced a sense of urgency to pass stool today?". The change from the baseline value was calculated as the difference between the mean score (percentage of days) of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Change From Baseline in Daily Number of Cutaneous Flushing Episodes	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24	Participants recorded the number of daily cutaneous flushing episodes experienced in the daily diary. The change from baseline value was calculated as the difference between the mean numbers of cutaneous flushing episodes of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels	Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21	Urinary 5-HIAA (u5-HIAA) is a standard test used in clinical practice to assess the neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. The change from baseline value for the Extension Period was calculated as the difference between mean change in 5-HIAA of the post-baseline interval (Weeks 20 to 21) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Change From Baseline in Stool Form/Consistency	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24	Participants assessed stool form/consistency in a daily diary using a 6-point scale (0-none, 1-hard, 2-firm, 3-soft, 4-loose, 5-watery). The change from the baseline value was calculated as the difference between a mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score and 5 indicates the worst score. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Change From Baseline in Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24	The severity of abdominal pain was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of abdominal pain or experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicate the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase	Baseline to Week 12	Clinically meaningful symptom reduction was defined as either: a) an average of \< 4 bowel movements per day over 15 consecutive days, b) a 50% reduction from baseline in the number of bowel movements, c) a positive response to the question regarding adequate relief, or d) a 50% reduction from baseline in the number of daily flushing episodes.