Back to resultsStudy of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy
Primary Purpose
Carcinoid Syndrome
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Telotristat etiprate
Octreotide LAR Depot
Placebo
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
- Symptoms not managed by stable-dose long-acting octreotide therapy (≥4 bowel movements per day)
- Ability to provide written informed consent
Exclusion Criteria:
- ≥12 high volume, watery bowel movements per day associated with a clinical syndrome of volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome
- 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
- Previous exposure to a tryptophan hydroxylase (TPH) inhibitor
- Administration of any investigational drug within 30 days of screening or any therapeutic protein or antibody within 90 days of screening
Sites / Locations
- Hematology Oncology Services of Arkansas
- UCSF Helen Diller Family Comprehensive Cancer Center
- St. Francis Medical Group Oncology and Hematology Specialists
- University of Iowa
- Dana Farber Cancer Institute
- Nebraska Methodist Hospital
- UT M.D. Anderson Cancer Center
- Texas Oncology - McAllen
- Texas Oncology - Weslaco
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Telotristat Etiprate 150 mg Core Phase
Telotristat Etiprate 250 mg Core Phase
Telotristat Etiprate 350 mg Core Phase
Telotristat Etiprate 500 mg Core Phase
Placebo Core Phase
Telotristat Etiprate Open-Label Extension Phase
Arm Description
Telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.
Telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
Outcomes
Primary Outcome Measures
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE 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. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
Number of Participants With Any TEAE in the Open-Label Extension Phase
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after receiving treatment.
Secondary Outcome Measures
Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day
Participants recorded the number of BMs per day in a daily diary. The total number of BMs per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.
Change From Baseline in Weekly Mean Stool Form
Participants recorded stool form in a daily diary using a 6-point scale (0-none,1-hard, 2-firm, 3-soft, 4-loose, 5-watery). A negative change from Baseline indicates improvement.
Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate
Participants recorded the sensation of urgency to defecate (Yes or No) in a daily diary. A negative change from Baseline indicates improvement.
Change From Baseline in Number of Cutaneous Flushing Episodes
Participants recorded the number of daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.
Change From Baseline in Severity of Abdominal Pain or Discomfort
Participants recorded the severity of abdominal pain or discomfort in a daily diary assessed using a 4-point scale (0-none, 1-mild, 2-moderate, 3-severe). A negative change from Baseline indicates improvement.
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-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. A negative change from Baseline indicates improvement.
Change From Baseline in Chromogranin A
Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.
Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome
Participants were asked to answer 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 number of participants who answered Yes are reported.
Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day
Participants recorded details (location and frequency of injection) of subcutaneous injections of rescue, short-acting octreotide, if taken, in the daily diary. A negative change from Baseline indicates improvement.
Time to First Rescue, Short-acting Octreotide
Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.
Number of Participants Experiencing Complete Response at Week 4
Complete Response to treatment was defined as one of the following: 1. Less than 4 bowel movements per day; or 2. A decrease in daily bowel movements that is ≥ 50% from baseline; or 3. A positive response to the global assessment 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?") for each of the last 2 weeks of the Treatment Period.
Full Information
NCT ID
NCT00853047
First Posted
February 25, 2009
Last Updated
December 3, 2018
Sponsor
Lexicon Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00853047
Brief Title
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy
Official Title
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Ascending, Multidose Study To Determine Safety and Tolerability of Orally Administered LX1606 in Subjects With Symptomatic Carcinoid Syndrome Refractory to Stable-Dose Octreotide Long-Acting Release Depot Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lexicon Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety and tolerability of telotristat etiprate (LX1606) versus a placebo control in participants with symptomatic carcinoid syndrome not managed by stable-dose long-acting octreotide therapy. Following determination of the maximally tolerated or effective dose, cohort expansion will occur to confirm effect on symptoms and safety profile.
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
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Telotristat Etiprate 150 mg Core Phase
Arm Type
Experimental
Arm Description
Telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Arm Title
Telotristat Etiprate 250 mg Core Phase
Arm Type
Experimental
Arm Description
Telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Arm Title
Telotristat Etiprate 350 mg Core Phase
Arm Type
Experimental
Arm Description
Telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Arm Title
Telotristat Etiprate 500 mg Core Phase
Arm Type
Experimental
Arm Description
Telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Arm Title
Placebo Core Phase
Arm Type
Experimental
Arm Description
Placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.
Arm Title
Telotristat Etiprate Open-Label Extension Phase
Arm Type
Experimental
Arm Description
Telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
Intervention Type
Drug
Intervention Name(s)
Telotristat etiprate
Other Intervention Name(s)
LX1606
Intervention Description
Telotristat etiprate capsules; orally 3 times daily.
Intervention Type
Drug
Intervention Name(s)
Octreotide LAR Depot
Intervention Description
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo-matching telotristat etiprate capsules; orally 3 times daily.
Primary Outcome Measure Information:
Title
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE 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. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.
Time Frame
Up to 4 Weeks Core Phase
Title
Number of Participants With Any TEAE in the Open-Label Extension Phase
Description
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after receiving treatment.
Time Frame
Up to 180 weeks in the open-label extension phase
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day
Description
Participants recorded the number of BMs per day in a daily diary. The total number of BMs per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Change From Baseline in Weekly Mean Stool Form
Description
Participants recorded stool form in a daily diary using a 6-point scale (0-none,1-hard, 2-firm, 3-soft, 4-loose, 5-watery). A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate
Description
Participants recorded the sensation of urgency to defecate (Yes or No) in a daily diary. A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Change From Baseline in Number of Cutaneous Flushing Episodes
Description
Participants recorded the number of daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Change From Baseline in Severity of Abdominal Pain or Discomfort
Description
Participants recorded the severity of abdominal pain or discomfort in a daily diary assessed using a 4-point scale (0-none, 1-mild, 2-moderate, 3-severe). A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)
Description
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. A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Change From Baseline in Chromogranin A
Description
Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome
Description
Participants were asked to answer 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 number of participants who answered Yes are reported.
Time Frame
Week 4
Title
Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day
Description
Participants recorded details (location and frequency of injection) of subcutaneous injections of rescue, short-acting octreotide, if taken, in the daily diary. A negative change from Baseline indicates improvement.
Time Frame
Baseline to Week 4
Title
Time to First Rescue, Short-acting Octreotide
Description
Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.
Time Frame
Baseline to Week 4
Title
Number of Participants Experiencing Complete Response at Week 4
Description
Complete Response to treatment was defined as one of the following: 1. Less than 4 bowel movements per day; or 2. A decrease in daily bowel movements that is ≥ 50% from baseline; or 3. A positive response to the global assessment 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?") for each of the last 2 weeks of the Treatment Period.
Time Frame
Baseline to Week 4
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
Symptoms not managed by stable-dose long-acting octreotide therapy (≥4 bowel movements per day)
Ability to provide written informed consent
Exclusion Criteria:
≥12 high volume, watery bowel movements per day associated with a clinical syndrome of volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome
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
Previous exposure to a tryptophan hydroxylase (TPH) inhibitor
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
Hematology Oncology Services of Arkansas
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
UCSF Helen Diller Family Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
St. Francis Medical Group Oncology and Hematology Specialists
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46237
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Nebraska Methodist Hospital
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
UT M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Oncology - McAllen
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503
Country
United States
Facility Name
Texas Oncology - Weslaco
City
Weslaco
State/Province
Texas
ZIP/Postal Code
78596
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27041406
Citation
Gelhorn HL, Kulke MH, O'Dorisio T, Yang QM, Jackson J, Jackson S, Boehm KA, Law L, Kostelec J, Auguste P, Lapuerta P. Patient-reported Symptom Experiences in Patients With Carcinoid Syndrome After Participation in a Study of Telotristat Etiprate: A Qualitative Interview Approach. Clin Ther. 2016 Apr;38(4):759-68. doi: 10.1016/j.clinthera.2016.03.002. Epub 2016 Mar 31.
Results Reference
derived
PubMed Identifier
25012985
Citation
Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, Freiman J, Frazier K, Jackson J, Yao JC, Kvols L, Lapuerta P, Zambrowicz B, Fleming D, Sands A. Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide. Endocr Relat Cancer. 2014 Oct;21(5):705-14. doi: 10.1530/ERC-14-0173. Epub 2014 Jul 10.
Results Reference
derived
Learn more about this trial
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy
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