TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome)

A Phase 3, Randomized, Placebo-controlled, Parallel Group, Multicenter, Double-blind Study to Evaluate the Efficacy and Safety of Telotristat Etiprate (LX1606) in Patients With Carcinoid Syndrome Not Adequately Controlled by Somatostatin Analog (SSA) Therapy

The primary objective of the study is to confirm that at least 1 or more doses of telotristat etiprate compared to placebo is effective in reducing the number of daily bowel movements (BMs) from baseline averaged over the 12-week double-blind portion (Treatment Period) of the trial in patients not adequately controlled by current SSA therapy.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Woodville South, Australia, 5011
    • Lexicon Investigational Site
  • New South Wales
    • Kogara, New South Wales, Australia, 2217
      • Lexicon Investigational Site
    • Saint Leanoards, New South Wales, Australia, 2065
      • Lexicon Investigational Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Lexicon Investigational Site
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Lexicon Investigational Site
  • Western Australia
    • Freemantle, Western Australia, Australia, 6160
      • Lexicon Investigational Site
• Belgium
  • Edegem, Belgium, B-2650
    • Lexicon Investigational Site
  • Gent, Belgium, 9000
    • Lexicon Investigational Site
  • Yvoir, Belgium, B-5530
    • Lexicon Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Lexicon Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H2Y9
      • Lexicon Investigational Site
• France
  • Clichy, France, 92118
    • Lexicon Investigational Site
  • Lille, France, 59037
    • Lexicon Investigational Site
  • Lyon, France, 69437
    • 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
  • Essen, Germany, 45147
    • 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
  • Munchen, Germany, 81377
    • Lexicon Investigational Site
  • Neuss, Germany, 41464
    • Lexicon Investigational Site
• Israel
  • Jerusalem, Israel, 91120
    • Lexicon Invetigational Site
• Italy
  • Bologna, Italy, 40138
    • Lexicon Investigational Site
  • Ferrara, Italy, 44124
    • Lexicon Investigational Site
  • Milan, Italy, 20089
    • Lexicon Investigational Site
  • Milan, Italy, 20141
    • Lexicon Investigational Site
  • Modena, Italy, 41126
    • Lexicon Investigational Site
  • Napoli, Italy, 80100
    • Lexicon Investigational Site
  • Orbassano, Italy, 10043
    • Lexicon Investigational Site
  • Perugia, Italy, 06156
    • Lexicon Investigational Site
  • Pisa, Italy, 56124
    • Lexicon Investigational Site
  • Rome, Italy, 00189
    • Lexicon Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Lexicon Investigational Site
  • Noord-Brahant, Netherlands, 5631BM
    • Lexicon Investigational Site
  • Noord-Holland, Netherlands, 1066CX
    • Lexicon Investigational Site
  • Zuid-Holland, Netherlands, 3015E
    • 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
  • Seville, Spain, 41013
    • Lexicon Investigational Site
• Sweden
  • Lund, Sweden, 22185
    • Lexicon Investigational Site
  • Uppsala, Sweden, 75185
    • Lexicon Investigational Site
• United Kingdom
  • Basingstoke-Hampshire, United Kingdom, RG249NA
    • Lexicon Investigational Site
  • Coventry, United Kingdom, CV2 2DX
    • Lexicon Investigational Site
  • Glasgow, United Kingdom, G12OYN
    • Lexicon Investigational Site
  • Headington-Oxford, United Kingdom, OX37LJ
    • Lexicon Investigational Site
  • London, United Kingdom, NW32QG
    • Lexicon Investigational Site
  • London, United Kingdom, SE59RS
    • 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
  • Alabama
    • Mobile, Alabama, United States, 36604
      • Lexicon Investigational Site
  • California
    • Palo Alto, California, United States, 94305
      • Lexicon Investigational Site
    • San Francisco, California, United States, 94115
      • 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
  • Louisiana
    • Kenner, Louisiana, United States, 70065
      • Lexicon Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Lexicon Investigational Site
    • Boston, Massachusetts, United States, 02114
      • Lexicon Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Lexicon Investigational Site
  • New York
    • Buffalo, New York, United States, 14263
      • Lexicon Investigational Site
    • New York, New York, United States, 10029
      • Lexicon Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Lexicon Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Lexicon Investigational Site
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Lexicon Investigational Site
    • Houston, Texas, United States, 77030
      • Lexicon Investigational Site
    • McAllen, Texas, United States, 78503
      • Lexicon Investigational Site

Participation Criteria

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:

• Histopathologically-confirmed, well-differentiated metastatic neuroendocrine tumor
• Documented history of carcinoid syndrome and currently experiencing ≥4 bowel movements per day during the Run-in period
• Currently receiving stable-dose somatostatin analog (SSA) therapy

• Minimum dose of long-acting release (LAR) or depot SSA therapy

  • Octreotide LAR at 30 mg every 4 weeks
  • Lanreotide Depot at 120 mg every 4 weeks
  • Patients who cannot tolerate SSA therapy at a level indicated above will be allowed to enter at their highest tolerated dose
• Ability and willingness to provide written informed consent

Exclusion Criteria:

• Presence of diarrhea attributed to any condition(s) other than carcinoid syndrome
• Karnofsky Performance status ≤60%
• Treatment with any tumor directed therapy, including interferon, chemotherapy, mechanistic target of rapamycin (mTOR) inhibitors <4 weeks prior to Screening, or hepatic embolization, radiotherapy, radiolabelled SSA, and/or tumor debulking <12 weeks prior to Screening
• History of short bowel syndrome (SBS)
• Clinically significant cardiac arrhythmia, bradycardia, tachycardia that would compromise patient safety or the outcome of the study
• Previous exposure to telotristat etiprate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 250 mg Telotristat Etiprate; Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	Drug: Telotristat etiprate; Telotristat etiprate tablets.; Other Names: LX1606; Drug: Placebo-matching telotristat etiprate; Placebo-matching telotristat etiprate tablets.
Experimental: 500 mg Telotristat Etiprate; Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	Drug: Telotristat etiprate; Telotristat etiprate tablets.; Other Names: LX1606; Drug: Placebo-matching telotristat etiprate; Placebo-matching telotristat etiprate tablets.
Placebo Comparator: Placebo; Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	Drug: Placebo-matching telotristat etiprate; Placebo-matching telotristat etiprate tablets.
Experimental: Telotristat Etiprate Open-Label Extension; Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.	Drug: Telotristat etiprate; Telotristat etiprate tablets.; Other Names: LX1606; Drug: Placebo-matching telotristat etiprate; Placebo-matching telotristat etiprate tablets.

What is the study measuring?

Primary 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
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 17.6 Weeks)
Number of Participants With 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 54.3 Weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 Week 12

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.
• Fust K, Maschio M, Kohli M, Singh S, Pritchard DM, Marteau F, Myrenfors P, Feuilly M. A Budget Impact Model of the Addition of Telotristat Ethyl Treatment to the Standard of Care in Patients with Uncontrolled Carcinoid Syndrome. Pharmacoeconomics. 2020 Jun;38(6):607-618. doi: 10.1007/s40273-020-00896-5.
• Hudgens S, Ramage J, Kulke M, Bergsland E, Anthony L, Caplin M, Oberg K, Pavel M, Gable J, Banks P, Yang QM, Lapuerta P. Evaluation of meaningful change in bowel movement frequency for patients with carcinoid syndrome. J Patient Rep Outcomes. 2019 Oct 26;3(1):64. doi: 10.1186/s41687-019-0153-y.
• Cella D, Beaumont JL, Hudgens S, Marteau F, Feuilly M, Houchard A, Lapuerta P, Ramage J, Pavel M, Horsch D, Kulke MH. Relationship Between Symptoms and Health-related Quality-of-life Benefits in Patients With Carcinoid Syndrome: Post Hoc Analyses From TELESTAR. Clin Ther. 2018 Dec;40(12):2006-2020.e2. doi: 10.1016/j.clinthera.2018.10.008. Epub 2018 Nov 24.
• Weickert MO, Kaltsas G, Horsch D, Lapuerta P, Pavel M, Valle JW, Caplin ME, Bergsland E, Kunz PL, Anthony LB, Grande E, Oberg K, Welin S, Lombard-Bohas C, Ramage JK, Kittur A, Yang QM, Kulke MH. Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome. Clin Ther. 2018 Jun;40(6):952-962.e2. doi: 10.1016/j.clinthera.2018.04.006. Epub 2018 May 1.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2013
• Primary Completion (Actual): March 21, 2016
• Study Completion (Actual): March 21, 2016

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: August 30, 2012
• First Posted (Estimate): September 3, 2012

Study Record Updates

• Last Update Posted (Actual): February 27, 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: LX1606.1-301-CS; LX1606.301 (Other Identifier: Lexicon Pharmaceuticals, Inc.); 2012-003460-47 (EudraCT Number)