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

Lexicon Pharmaceuticals23 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Carcinoid Syndrome

Interventions

Telotristat etiprateDRUG

Telotristat etiprate capsules; orally 3 times daily.

Octreotide LAR DepotDRUG

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

PlaceboDRUG

Placebo-matching telotristat etiprate capsules; orally 3 times daily.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (9)

Hematology Oncology Services of Arkansas

Little Rock, Arkansas, United States

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

St. Francis Medical Group Oncology and Hematology Specialists

Indianapolis, Indiana, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to 4 Weeks Core Phase

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.

Time frame: Up to 180 weeks in the open-label extension phase

Secondary Outcomes

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.

Time frame: Baseline to Week 4

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.

Time frame: Baseline to Week 4

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.

Time frame: Baseline to Week 4

Change From Baseline in Number of Cutaneous Flushing Episodes

Data from ClinicalTrials.gov

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University of Iowa

Iowa City, Iowa, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Nebraska Methodist Hospital

Omaha, Nebraska, United States

UT M.D. Anderson Cancer Center

Houston, Texas, United States

Texas Oncology - McAllen

McAllen, Texas, United States

Texas Oncology - Weslaco

Weslaco, Texas, United States

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

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.

Time frame: Baseline to Week 4

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.

Time frame: Baseline to Week 4

Change From Baseline in Chromogranin A

Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.

Time frame: Baseline to Week 4

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.

Time frame: Week 4

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 frame: Baseline to Week 4

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.

Time frame: Baseline to Week 4

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.

Time frame: Baseline to Week 4