Back to resultsStudy of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome
Primary Purpose
Carcinoid Syndrome
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Telotristat etiprate
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoid Syndrome
Eligibility Criteria
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
Sites / Locations
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Telotristat etiprate - Core Phase
Telotristat etiprate - Extension Period
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs 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
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
Change From Baseline in Number of Bowel Movements (BMs)
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.
Change From Baseline in Stool Form/Consistency
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 Percentage of Days With Sensation of Urgency to Defecate
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 Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)
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.
Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome
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 Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)
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.
Change From Baseline in Daily Number of Cutaneous Flushing Episodes
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.
Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase
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.
Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels
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.
Full Information
NCT ID
NCT01104415
First Posted
April 12, 2010
Last Updated
February 26, 2019
Sponsor
Lexicon Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01104415
Brief Title
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome
Official Title
A Phase 2, Open-Label, Multi-Center, Serial Ascending-Dose, Dose-Finding Study to Evaluate the Safety and Tolerability of LX1606 in Subjects With Symptomatic Carcinoid Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
June 15, 2010 (Actual)
Primary Completion Date
February 12, 2014 (Actual)
Study Completion Date
February 12, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lexicon Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoid Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Telotristat etiprate - Core Phase
Arm Type
Experimental
Arm Description
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.
Arm Title
Telotristat etiprate - Extension Period
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Telotristat etiprate
Other Intervention Name(s)
LX1606 Hippurate
Intervention Description
Telotristat etiprate capsules orally three times daily.
Primary Outcome Measure Information:
Title
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase
Description
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.
Time Frame
Baseline up to Week 12 in the Core Phase
Title
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period
Description
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.
Time Frame
Up to 124 Weeks in the Extension Period
Secondary Outcome Measure Information:
Title
Change From Baseline in Number of Bowel Movements (BMs)
Description
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.
Time Frame
Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Title
Change From Baseline in Stool Form/Consistency
Description
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.
Time Frame
Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Title
Change From Baseline in Percentage of Days With Sensation of Urgency to Defecate
Description
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.
Time Frame
Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Title
Change From Baseline in Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)
Description
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.
Time Frame
Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Title
Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome
Description
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.
Time Frame
Core Phase: Weeks 9-12; Extension Period: Week 24
Title
Change From Baseline in Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)
Description
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.
Time Frame
Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Title
Change From Baseline in Daily Number of Cutaneous Flushing Episodes
Description
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.
Time Frame
Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Title
Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase
Description
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.
Time Frame
Baseline to Week 12
Title
Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels
Description
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.
Time Frame
Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pablo LaPuerta, MD
Organizational Affiliation
Lexicon Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Lexicon Investigational Site
City
Bad Berka
Country
Germany
Facility Name
Lexicon Investigational Site
City
Berlin
Country
Germany
Facility Name
Lexicon Investigational Site
City
Halle
Country
Germany
Facility Name
Lexicon Investigational Site
City
Lubeck
Country
Germany
Facility Name
Lexicon Investigational Site
City
Marburg
Country
Germany
Facility Name
Lexicon Investigational Site
City
Munich
Country
Germany
Facility Name
Lexicon Investigational Site
City
Basingstoke
Country
United Kingdom
Facility Name
Lexicon Investigational Site
City
Cambridge
Country
United Kingdom
Facility Name
Lexicon Investigational Site
City
London
Country
United Kingdom
Facility Name
Lexicon Investigational Site
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25636046
Citation
Pavel M, Horsch D, Caplin M, Ramage J, Seufferlein T, Valle J, Banks P, Lapuerta P, Sands A, Zambrowicz B, Fleming D, Wiedenmann B. Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1511-9. doi: 10.1210/jc.2014-2247. Epub 2015 Jan 30.
Results Reference
derived
Learn more about this trial
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome
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