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

December 3, 2018 updated by: Lexicon Pharmaceuticals

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

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Hematology Oncology Services of Arkansas
    • California
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • St. Francis Medical Group Oncology and Hematology Specialists
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • UT M.D. Anderson Cancer Center
      • McAllen, Texas, United States, 78503
        • Texas Oncology - McAllen
      • Weslaco, Texas, United States, 78596
        • Texas Oncology - Weslaco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Telotristat Etiprate 150 mg Core Phase
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.
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
  • LX1606
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
Experimental: Telotristat Etiprate 250 mg Core Phase
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.
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
  • LX1606
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
Experimental: Telotristat Etiprate 350 mg Core Phase
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.
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
  • LX1606
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
Experimental: Telotristat Etiprate 500 mg Core Phase
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.
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
  • LX1606
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
Experimental: Placebo Core Phase
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.
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
Drug: Placebo
Placebo-matching telotristat etiprate capsules; orally 3 times daily.
Experimental: Telotristat Etiprate Open-Label Extension Phase
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).
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
  • LX1606
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase
Time Frame: 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.
Up to 4 Weeks Core Phase
Number of Participants With Any TEAE in the Open-Label Extension Phase
Time Frame: 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.
Up to 180 weeks in the open-label extension phase

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day
Time Frame: 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.
Baseline to Week 4
Change From Baseline in Weekly Mean Stool Form
Time Frame: 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.
Baseline to Week 4
Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate
Time Frame: 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.
Baseline to Week 4
Change From Baseline in Number of Cutaneous Flushing Episodes
Time Frame: 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.
Baseline to Week 4
Change From Baseline in Severity of Abdominal Pain or Discomfort
Time Frame: 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.
Baseline to Week 4
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)
Time Frame: 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.
Baseline to Week 4
Change From Baseline in Chromogranin A
Time Frame: Baseline to Week 4
Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.
Baseline to Week 4
Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome
Time Frame: 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.
Week 4
Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day
Time Frame: 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.
Baseline to Week 4
Time to First Rescue, Short-acting Octreotide
Time Frame: Baseline to Week 4
Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.
Baseline to Week 4
Number of Participants Experiencing Complete Response at Week 4
Time Frame: 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.
Baseline to Week 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lexicon Pharmaceuticals

Investigators

  • Study Director: Pablo LaPuerta, MD, Lexicon Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

June 1, 2014

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

February 25, 2009

First Submitted That Met QC Criteria

February 25, 2009

First Posted (Estimate)

February 27, 2009

Study Record Updates

Last Update Posted (Actual)

December 26, 2018

Last Update Submitted That Met QC Criteria

December 3, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LX1606.1-202-CS
  • LX1606.202 (Other Identifier: Lexicon Pharmaceuticals, Inc.)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Carcinoid Syndrome

Clinical Trials on Telotristat etiprate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ireland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe