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

NCT01677910 | Completed Phase 3 Results DMC

• 3 other identifiers: LX1606.1-301-CSLX1606.3012012-003460-47
• Study Type: interventional
• Target: 135
• Locations: 12 countries
• Sites: 75

Brief Summary

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.

Conditions

Carcinoid Syndrome

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels

  Baseline and Week 12

• Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points

  Baseline and 12 Weeks

• Change From Baseline in Abdominal Pain Averaged Across All Time-Points

  Baseline and 12 Weeks

Study Arms (4)

250 mg Telotristat Etiprate

EXPERIMENTAL

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; Drug: Placebo-matching telotristat etiprate

500 mg Telotristat Etiprate

EXPERIMENTAL

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; Drug: Placebo-matching telotristat etiprate

Placebo

PLACEBO COMPARATOR

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

Telotristat Etiprate Open-Label Extension

EXPERIMENTAL

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; Drug: Placebo-matching telotristat etiprate

Interventions

Telotristat etiprate DRUG

Telotristat etiprate tablets.

Also known as: LX1606

250 mg Telotristat Etiprate; 500 mg Telotristat Etiprate; Telotristat Etiprate Open-Label Extension

Placebo-matching telotristat etiprate DRUG

Placebo-matching telotristat etiprate tablets.

250 mg Telotristat Etiprate; 500 mg Telotristat Etiprate; Placebo; Telotristat Etiprate Open-Label Extension

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead

Study Sites (75)

Lexicon Investigational Site

Mobile, Alabama, 36604, United States

Location

Lexicon Investigational Site

Palo Alto, California, 94305, United States

Location

Lexicon Investigational Site

San Francisco, California, 94115, United States

Location

Lexicon Investigational Site

Orlando, Florida, 32806, United States

Location

Lexicon Investigational Site

Iowa City, Iowa, 52242, United States

Location

Lexicon Investigational Site

Lexington, Kentucky, 40536, United States

Location

Lexicon Investigational Site

Kenner, Louisiana, 70065, United States

Location

Lexicon Investigational Site

Boston, Massachusetts, 02114, United States

Location

Lexicon Investigational Site

Boston, Massachusetts, 02215, United States

Location

Lexicon Investigational Site

Omaha, Nebraska, 68114, United States

Location

Lexicon Investigational Site

Buffalo, New York, 14263, United States

Location

Lexicon Investigational Site

New York, New York, 10029, United States

Location

Lexicon Investigational Site

Durham, North Carolina, 27710, United States

Location

Lexicon Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

Lexicon Investigational Site

Fort Worth, Texas, 76104, United States

Location

Lexicon Investigational Site

Houston, Texas, 77030, United States

Location

Lexicon Investigational Site

McAllen, Texas, 78503, United States

Location

Lexicon Investigational Site

Kogara, New South Wales, 2217, Australia

Location

Lexicon Investigational Site

Saint Leanoards, New South Wales, 2065, Australia

Location

Lexicon Investigational Site

Herston, Queensland, 4029, Australia

Location

Lexicon Investigational Site

Fitzroy, Victoria, 3065, Australia

Location

Lexicon Investigational Site

Freemantle, Western Australia, 6160, Australia

Location

Lexicon Investigational Site

Woodville South, 5011, Australia

Location

Lexicon Investigational Site

Edegem, B-2650, Belgium

Location

Lexicon Investigational Site

Ghent, 9000, Belgium

Location

Lexicon Investigational Site

Yvoir, B-5530, Belgium

Location

Lexicon Investigational Site

Calgary, Alberta, T2N 4N2, Canada

Location

Lexicon Investigational Site

Halifax, Nova Scotia, B3H2Y9, Canada

Location

Lexicon Investigational Site

Clichy, 92118, France

Location

Lexicon Investigational Site

Lille, 59037, France

Location

Lexicon Investigational Site

Lyon, 69437, France

Location

Lexicon Investigational Site

Marseille, 13385, France

Location

Lexicon Investigational Site

Strasbourg, 67098, France

Location

Lexicon Investigational Site

Villejuif, 94805, France

Location

Lexicon Investigational Site

Bad Berka, 99437, Germany

Location

Lexicon Investigational Site

Berlin, 13353, Germany

Location

Lexicon Investigational Site

Essen, 45147, Germany

Location

Lexicon Investigational Site

Hamburg, 20246, Germany

Location

Lexicon Investigational Site

Heidelberg, 69120, Germany

Location

Lexicon Investigational Site

Lübeck, 23538, Germany

Location

Lexicon Investigational Site

Mainz, 55131, Germany

Location

Lexicon Investigational Site

Marburg, 35043, Germany

Location

Lexicon Investigational Site

München, 81377, Germany

Location

Lexicon Investigational Site

Neuss, 41464, Germany

Location

Lexicon Invetigational Site

Jerusalem, 91120, Israel

Location

Lexicon Investigational Site

Bologna, 40138, Italy

Location

Lexicon Investigational Site

Ferrara, 44124, Italy

Location

Lexicon Investigational Site

Milan, 20089, Italy

Location

Lexicon Investigational Site

Milan, 20141, Italy

Location

Lexicon Investigational Site

Modena, 41126, Italy

Location

Lexicon Investigational Site

Napoli, 80100, Italy

Location

Lexicon Investigational Site

Orbassano, 10043, Italy

Location

Lexicon Investigational Site

Perugia, 06156, Italy

Location

Lexicon Investigational Site

Pisa, 56124, Italy

Location

Lexicon Investigational Site

Rome, 00189, Italy

Location

Lexicon Investigational Site

Amsterdam, 1105 AZ, Netherlands

Location

Lexicon Investigational Site

Noord-Brahant, 5631BM, Netherlands

Location

Lexicon Investigational Site

Noord-Holland, 1066CX, Netherlands

Location

Lexicon Investigational Site

Zuid-Holland, 3015E, Netherlands

Location

Lexicon Investigational Site

Barcelona, 08035, Spain

Location

Lexicon Investigational Site

Barcelona, 08907, Spain

Location

Lexicon Investigational Site

Madrid, 28034, Spain

Location

Lexicon Investigational Site

Madrid, 28040, Spain

Location

Lexicon Investigational Site

Seville, 41013, Spain

Location

Lexicon Investigational Site

Lund, 22185, Sweden

Location

Lexicon Investigational Site

Uppsala, 75185, Sweden

Location

Lexicon Investigational Site

Basingstoke-Hampshire, RG249NA, United Kingdom

Location

Lexicon Investigational Site

Coventry, CV2 2DX, United Kingdom

Location

Lexicon Investigational Site

Glasgow, G12OYN, United Kingdom

Location

Lexicon Investigational Site

Headington-Oxford, OX37LJ, United Kingdom

Location

Lexicon Investigational Site

London, NW32QG, United Kingdom

Location

Lexicon Investigational Site

London, SE59RS, United Kingdom

Location

Lexicon Investigational Site

London, W12 OHS, United Kingdom

Location

Lexicon Investigational Site

Manchester, M204BX, United Kingdom

Location

Lexicon Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Publications (6)

• 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.

  PMID: 34598813 DERIVED

• 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.

  PMID: 32157590 DERIVED

• 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.

  PMID: 32146619 DERIVED

• 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.

  PMID: 31655936 DERIVED

• 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.

  PMID: 30477789 DERIVED

• 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.

  PMID: 29724499 DERIVED

MeSH Terms

Conditions

Serotonin Syndrome

Interventions

telotristat

Condition Hierarchy (Ancestors)

Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders

Results Point of Contact

• Title: Pablo Lapuerta, MD
• Organization: Lexicon Pharmaceuticals, Inc.

plapuerta@lexpharma.com

Study Officials

• Pablo Lapuerta, MD

  Lexicon Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants were randomized to one of three treatment arms in the double-blind treatment period. After completion of the double-blind treatment period, participants entered an open-label treatment period.

Study Record Dates

• First Submitted: August 30, 2012
• First Posted: September 3, 2012
• Study Start: January 8, 2013
• Primary Completion: March 21, 2016
• Study Completion: March 21, 2016
• Last Updated: February 27, 2018
• Results First Posted: September 18, 2017

Record last verified: 2018-01

Locations

BE (3); ES (5); US (17); CA (2); AU (6); IT (10); FR (6); GB (9); IL (1); DE (10); NL (4); SE (2)