Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy
- Conditions
- Carcinoid Syndrome
- Interventions
- Registration Number
- NCT00853047
- Lead Sponsor
- Lexicon Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
- 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
- ≥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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Telotristat Etiprate 150 mg Core Phase Telotristat etiprate 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 250 mg Core Phase Octreotide LAR Depot 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 350 mg Core Phase Octreotide LAR Depot 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 500 mg Core Phase Octreotide LAR Depot 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 Core Phase Placebo 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 250 mg Core Phase Telotristat etiprate 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 350 mg Core Phase Telotristat etiprate 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 500 mg Core Phase Telotristat etiprate 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. Telotristat Etiprate Open-Label Extension Phase Telotristat etiprate 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). Telotristat Etiprate 150 mg Core Phase Octreotide LAR Depot 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. Placebo Core Phase Octreotide LAR Depot 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 Open-Label Extension Phase Octreotide LAR Depot 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).
- Primary Outcome Measures
Name Time Method Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase Up to 4 Weeks 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 Up to 180 weeks 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
Name Time Method Change From Baseline in Weekly Mean Stool Form Baseline to Week 4 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 Number of Cutaneous Flushing Episodes Baseline to Week 4 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.
Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome Week 4 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.
Number of Participants Experiencing Complete Response at Week 4 Baseline to 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.
Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day Baseline to Week 4 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 Chromogranin A Baseline to Week 4 Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.
Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day Baseline to Week 4 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 Baseline to Week 4 Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.
Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate Baseline to Week 4 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 Severity of Abdominal Pain or Discomfort Baseline to Week 4 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) Baseline to Week 4 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.
Trial Locations
- Locations (9)
University of Iowa
🇺🇸Iowa City, Iowa, United States
Texas Oncology - Weslaco
🇺🇸Weslaco, Texas, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Hematology Oncology Services of Arkansas
🇺🇸Little Rock, Arkansas, United States
St. Francis Medical Group Oncology and Hematology Specialists
🇺🇸Indianapolis, Indiana, United States
UT M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Texas Oncology - McAllen
🇺🇸McAllen, Texas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States