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

Carcinoid Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01104415
• Other study ID #: LX1606.1-203-CS
• Secondary ID: LX1606.203, LX10
• Status: Completed
• Phase: Phase 2
• Start date: June 15, 2010
• Est. completion date: February 12, 2014

Study information

• Verified date: February 2019
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: February 12, 2014
• Est. primary completion date: February 12, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoid Syndrome
• Carcinoid Tumor
• Malignant Carcinoid Syndrome
• Serotonin Syndrome
• Syndrome

Intervention

Drug:
• Telotristat etiprate
Telotristat etiprate capsules orally three times daily.

Locations

Country	Name	City	State
Germany	Lexicon Investigational Site	Bad Berka
Germany	Lexicon Investigational Site	Berlin
Germany	Lexicon Investigational Site	Halle
Germany	Lexicon Investigational Site	Lubeck
Germany	Lexicon Investigational Site	Marburg
Germany	Lexicon Investigational Site	Munich
United Kingdom	Lexicon Investigational Site	Basingstoke
United Kingdom	Lexicon Investigational Site	Cambridge
United Kingdom	Lexicon Investigational Site	London
United Kingdom	Lexicon Investigational Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to Week 12 in the Core Phase
Primary	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.	Up to 124 Weeks in the Extension Period
Secondary	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.	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Secondary	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.	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Secondary	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.	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Secondary	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.	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Secondary	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.	Core Phase: Weeks 9-12; Extension Period: Week 24
Secondary	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.	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Secondary	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.	Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Secondary	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.	Baseline to Week 12
Secondary	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.	Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21