- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01104415
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome
February 26, 2019 updated by: Lexicon Pharmaceuticals
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
The purpose of the study is to evaluate the safety and tolerability of orally administered telotristat etiprate (LX1606) in participants with symptomatic carcinoid syndrome.
Study Overview
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Bad Berka, Germany
- Lexicon Investigational Site
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Berlin, Germany
- Lexicon Investigational Site
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Halle, Germany
- Lexicon Investigational Site
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Lubeck, Germany
- Lexicon Investigational Site
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Marburg, Germany
- Lexicon Investigational Site
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Munich, Germany
- Lexicon Investigational Site
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Basingstoke, United Kingdom
- Lexicon Investigational Site
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Cambridge, United Kingdom
- Lexicon Investigational Site
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London, United Kingdom
- Lexicon Investigational Site
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Manchester, United Kingdom
- Lexicon Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Telotristat etiprate - Core Phase
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.
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Telotristat etiprate capsules orally three times daily.
Other Names:
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Experimental: Telotristat etiprate - 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.
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Telotristat etiprate capsules orally three times daily.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase
Time Frame: Baseline up to Week 12 in the Core Phase
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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.
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Baseline up to Week 12 in the Core Phase
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Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period
Time Frame: Up to 124 Weeks in the Extension Period
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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.
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Up to 124 Weeks in the Extension Period
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Number of Bowel Movements (BMs)
Time Frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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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.
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Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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Change From Baseline in Stool Form/Consistency
Time Frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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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.
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Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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Change From Baseline in Percentage of Days With Sensation of Urgency to Defecate
Time Frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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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.
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Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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Change From Baseline in Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)
Time Frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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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.
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Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome
Time Frame: Core Phase: Weeks 9-12; Extension Period: Week 24
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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.
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Core Phase: Weeks 9-12; Extension Period: Week 24
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Change From Baseline in Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)
Time Frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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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.
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Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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Change From Baseline in Daily Number of Cutaneous Flushing Episodes
Time Frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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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.
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Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
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Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase
Time Frame: Baseline to Week 12
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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.
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Baseline to Week 12
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Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels
Time Frame: Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21
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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.
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Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Pablo LaPuerta, MD, Lexicon Pharmaceuticals, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 15, 2010
Primary Completion (Actual)
February 12, 2014
Study Completion (Actual)
February 12, 2014
Study Registration Dates
First Submitted
April 12, 2010
First Submitted That Met QC Criteria
April 13, 2010
First Posted (Estimate)
April 15, 2010
Study Record Updates
Last Update Posted (Actual)
March 15, 2019
Last Update Submitted That Met QC Criteria
February 26, 2019
Last Verified
February 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Disease
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Drug-Related Side Effects and Adverse Reactions
- Syndrome
- Carcinoid Tumor
- Malignant Carcinoid Syndrome
- Serotonin Syndrome
Other Study ID Numbers
- LX1606.1-203-CS
- LX1606.203, LX1032 (Other Identifier: Lexicon Pharmaceuticals, Inc.)
- 2009-016973-13 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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