Telotristat Etiprate for Carcinoid Syndrome Therapy (TELECAST)

A Phase 3, Randomized, Placebo-controlled, Multicenter, Double-blind Study to Evaluate the Safety and Efficacy of Telotristat Etiprate (LX1606) in Patients With Carcinoid Syndrome

The purpose of the study is to evaluate the effect of telotristat etiprate versus placebo on the incidence of treatment-emergent adverse events and on 5-hydroxyindoleacetic acid (5-HIAA) levels.

Study Overview

• Status: Completed
• Conditions: Carcinoid Syndrome
• Intervention / Treatment: Drug: Telotristat etiprate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogara, New South Wales, Australia, 2217
      • Lexicon Investigational Site
    • St. Leonards, New South Wales, Australia, 2065
      • Lexicon Investigational Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Lexicon Investigational Site
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Lexicon Investigational Site
• Belgium
  • Edegem, Belgium, B-2650
    • Lexicon Investigational Site
  • Gent, Belgium, 9000
    • Lexicon Investigational Site
  • Yvoir, Belgium, 5530
    • Lexicon Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N2
      • Lexicon Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B0J1N0
      • Lexicon Investigational Site
• France
  • Clichy, France, 92118
    • Lexicon Investigational Site
  • Lille, France, 59037
    • Lexicon Investigational Site
  • Lyon, France, 69347
    • Lexicon Investigational Site
  • Marseille, France, 13385
    • Lexicon Investigational Site
  • Strasbourg, France, 67098
    • Lexicon Investigational Site
  • Villejuif, France, 94805
    • Lexicon Investigational Site
• Germany
  • Bad Berka, Germany, 99437
    • Lexicon Investigational Site
  • Berlin, Germany, 13353
    • Lexicon Investigational Site
  • Hamburg, Germany, 20246
    • Lexicon Investigational Site
  • Heidelberg, Germany, 69120
    • Lexicon Investigational Site
  • Lubeck, Germany, 23538
    • Lexicon Investigational Site
  • Mainz, Germany, 55131
    • Lexicon Investigational Site
  • Marburg, Germany, 35043
    • Lexicon Investigational Site
  • Munich, Germany, 81377
    • Lexicon Investigational Site
  • Neuss, Germany, 41464
    • Lexicon Investigational Site
• Israel
  • Jerusalem, Israel, 91120
    • Lexicon Investigational Site
• Netherlands
  • Noord Brahant, Netherlands, 5631BM
    • Lexicon Investigational Site
  • Rotterdam, Netherlands, 3015 CE
    • Lexicon Investigative Site
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066X
      • Lexicon Investigational Site
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Lexicon Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Lexicon Investigational Site
  • Barcelona, Spain, 08907
    • Lexicon Investigational Site
  • Madrid, Spain, 28034
    • Lexicon Investigational Site
  • Madrid, Spain, 28040
    • Lexicon Investigational Site
  • Sevilla, Spain, 41013
    • Lexicon Investigational Site
• Sweden
  • Uppsala, Sweden, 75185
    • Lexicon Investigational Site
• United Kingdom
  • Basingstoke Hampshire, United Kingdom, RG249NA
    • Lexicon Investigational Site
  • Coventry, United Kingdom, CV22DX
    • Lexicon Investigational Site
  • London, United Kingdom, SE59RS
    • Lexicon Investigational Site
  • London, United Kingdom, NW3 2QG
    • Lexicon Investigational Site
  • London, United Kingdom, W12 OHS
    • Lexicon Investigational Site
  • Manchester, United Kingdom, M204BX
    • Lexicon Investigational Site
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Lexicon Investigational Site
• United States
  • California
    • Stanford, California, United States, 94305
      • Lexicon Investigational Site
  • Florida
    • Orlando, Florida, United States, 32806
      • Lexicon Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Lexicon Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Lexicon Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Lexicon Investigational Site
  • New York
    • Buffalo, New York, United States, 14263
      • Lexicon Investigational Site
    • New York, New York, United States, 10029
      • Lexicon Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ≥ 18 years of age
• All patients of reproductive potential must agree to use an adequate method of contraception during the study and for 12 weeks after the Follow-up visit.
• Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor
• Documented history of carcinoid syndrome
• Patient is able and willing to provide written informed consent prior to participation

Exclusion Criteria:

• Presence of diarrhea attributed to any condition other than carcinoid syndrome.
• Presence of 12 or more watery bowel movements per day
• Positive stool examination for enteric pathogens, pathogenic ova or parasites, of Clostridium difficile at Screening
• Karnofsky Performance Status ≤ 60%
• Presence of any clinically significant laboratory, medical history, or physical examination findings deemed unacceptable by the Investigator
• A history of short bowel syndrome
• History of constipation within 2 years of Screening
• Life expectancy < 12 months from Screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 250 mg Telotristat Etiprate; Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.	Drug: Telotristat etiprate; Telotristat etiprate tablets; Other Names: LX1606; Drug: Placebo; Placebo-matching telotristat etiprate tablets
Experimental: 500 mg Telotristat Etiprate; Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.	Drug: Telotristat etiprate; Telotristat etiprate tablets; Other Names: LX1606; Drug: Placebo; Placebo-matching telotristat etiprate tablets
Placebo Comparator: Placebo; Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.	Drug: Placebo; Placebo-matching telotristat etiprate tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period	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.	First dose of study drug to within 30 days of last dose of study drug in the Double-Blind Treatment Period (Up to 17.1 Weeks)
Primary: Percent Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels	u5-HIAA is a standard test used in clinical practice to assess neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. A negative change from Baseline indicates improvement.	Baseline and 12 Weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Extension Period	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.	First dose of study drug to within 30 days of last dose of study drug in the Open-Label Extension Period (Up to 52.6 Weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks	Participants recorded the number of bowel movements per day in a daily diary. The total number of BMs per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.	Baseline and 12 weeks
Change From Baseline in Stool Form/Consistency Averaged Across All Time-Points	Participants assessed stool form/consistency of a BM using the Bristol Stool Form Scale where: 1=hard lumps to 7=watery liquid. The daily scores were averaged over the 12-week period. A negative change indicates improvement.	Baseline and 12 Weeks
Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points	Participants recorded the number daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.	Baseline and 12 Weeks
Change From Baseline in Abdominal Pain Averaged Across All Time-Points	Participants recorded abdominal pain in a daily diary. Participants evaluated the level of any abdominal pain using an 11-point numeric rating scale, where: 0=no pain to 10=worst pain ever experienced. The average daily abdominal pain was averaged over the 12-week period. A negative change from Baseline indicates improvement.	Baseline and 12 Weeks
Change in the Frequency of Rescue Short-acting, Somatostatin Analog (SSA) Used to Treat Carcinoid Syndrome Symptoms Averaged Across All Time-Points	The frequency (the number of times) the participant used rescue with SSA to control symptoms was recorded in a daily diary. The daily number of rescue treatments with SSA was averaged over the 12- week period. A negative change from Baseline (less use of SSA) indicates improvement.	Baseline and 12 weeks
Change From Baseline in the Number of Daily BMs Averaged Over the 12-Week Double-Blind Period, Among Participants Who Were Not Receiving SSA Therapy at Baseline	Participants recorded the number of bowel movements per day in a daily diary. The total number of BMs per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.	Baseline and 12 Weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Srirajaskanthan R, Pavel M, Kulke M, Clement D, Houchard A, Keeber L, Weickert MO. Weight Maintenance up to 48 Weeks in Patients With Carcinoid Syndrome Treated With Telotristat Ethyl: Pooled Data From the Open-Label Extensions of the Phase III Clinical Trials TELESTAR and TELECAST. Clin Ther. 2021 Oct;43(10):1779-1785. doi: 10.1016/j.clinthera.2021.08.014. Epub 2021 Sep 28.
• Dillon JS, Kulke MH, Horsch D, Anthony LB, Warner RRP, Bergsland E, Welin S, O'Dorisio TM, Kunz PL, McKee C, Lapuerta P, Banks P, Pavel M. Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome. J Gastrointest Cancer. 2021 Mar;52(1):212-221. doi: 10.1007/s12029-020-00375-2.
• Pavel M, Gross DJ, Benavent M, Perros P, Srirajaskanthan R, Warner RRP, Kulke MH, Anthony LB, Kunz PL, Horsch D, Weickert MO, Lapuerta P, Jiang W, Kassler-Taub K, Wason S, Fleming R, Fleming D, Garcia-Carbonero R. Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial. Endocr Relat Cancer. 2018 Mar;25(3):309-322. doi: 10.1530/ERC-17-0455. Epub 2018 Jan 12.

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2014
• Primary Completion (Actual): March 29, 2016
• Study Completion (Actual): March 29, 2016

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimate): February 14, 2014

Study Record Updates

• Last Update Posted (Actual): February 26, 2018
• Last Update Submitted That Met QC Criteria: January 26, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Drug-Related Side Effects and Adverse Reactions; Syndrome; Carcinoid Tumor; Malignant Carcinoid Syndrome; Serotonin Syndrome
• Other Study ID Numbers: LX1606.1-303-CS; LX1606.303 (Other Identifier: Lexicon Pharmaceuticals, Inc.); 2013-001543-31 (EudraCT Number)