Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy

Carcinoid Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00853047
• Other study ID #: LX1606.1-202-CS
• Secondary ID: LX1606.202
• Status: Completed
• Phase: Phase 2
• Start date: March 2009
• Est. completion date: June 2014

Study information

• Verified date: October 2018
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 2014
• Est. primary completion date: June 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

• 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
• Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
• Placebo
Placebo-matching telotristat etiprate capsules; orally 3 times daily.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	UT M.D. Anderson Cancer Center	Houston	Texas
United States	St. Francis Medical Group Oncology and Hematology Specialists	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Hematology Oncology Services of Arkansas	Little Rock	Arkansas
United States	Texas Oncology - McAllen	McAllen	Texas
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Texas Oncology - Weslaco	Weslaco	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 4 Weeks Core Phase
Primary	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.	Up to 180 weeks in the open-label extension phase
Secondary	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.	Baseline to Week 4
Secondary	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.	Baseline to Week 4
Secondary	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.	Baseline to Week 4
Secondary	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.	Baseline to Week 4
Secondary	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.	Baseline to Week 4
Secondary	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.	Baseline to Week 4
Secondary	Change From Baseline in Chromogranin A	Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.	Baseline to Week 4
Secondary	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.	Week 4
Secondary	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.	Baseline to Week 4
Secondary	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.	Baseline to Week 4
Secondary	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.	Baseline to Week 4