Telotristat Etiprate for Carcinoid Syndrome Therapy

NCT02063659 | Completed Phase 3 Results DMC

• 3 other identifiers: LX1606.1-303-CSLX1606.3032013-001543-31
• Study Type: interventional
• Target: 76
• Locations: 11 countries
• Sites: 50

Brief Summary

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.

Conditions

Carcinoid Syndrome

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks

  Baseline and 12 weeks

• Change From Baseline in Stool Form/Consistency Averaged Across All Time-Points

  Baseline and 12 Weeks

• 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

• Change in the Frequency of Rescue Short-acting, Somatostatin Analog (SSA) Used to Treat Carcinoid Syndrome Symptoms Averaged Across All Time-Points

  Baseline and 12 weeks

Study Arms (3)

250 mg Telotristat Etiprate

EXPERIMENTAL

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; Drug: Placebo

500 mg Telotristat Etiprate

EXPERIMENTAL

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; Drug: Placebo

Placebo

PLACEBO COMPARATOR

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

Interventions

Telotristat etiprate DRUG

Telotristat etiprate tablets

Also known as: LX1606

250 mg Telotristat Etiprate; 500 mg Telotristat Etiprate

Placebo DRUG

Placebo-matching telotristat etiprate tablets

250 mg Telotristat Etiprate; 500 mg Telotristat Etiprate; Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead

Study Sites (50)

Lexicon Investigational Site

Stanford, California, 94305, 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

Boston, Massachusetts, 02215, 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

Philadelphia, Pennsylvania, 19104, United States

Location

Lexicon Investigational Site

Kogara, New South Wales, 2217, Australia

Location

Lexicon Investigational Site

St Leonards, New South Wales, 2065, Australia

Location

Lexicon Investigational Site

Herston, Queensland, 4029, Australia

Location

Lexicon Investigational Site

East Melbourne, Victoria, 3002, Australia

Location

Lexicon Investigational Site

Edegem, B-2650, Belgium

Location

Lexicon Investigational Site

Ghent, 9000, Belgium

Location

Lexicon Investigational Site

Yvoir, 5530, Belgium

Location

Lexicon Investigational Site

Calgary, Alberta, T2N4N2, Canada

Location

Lexicon Investigational Site

Halifax, Nova Scotia, B0J1N0, Canada

Location

Lexicon Investigational Site

Clichy, 92118, France

Location

Lexicon Investigational Site

Lille, 59037, France

Location

Lexicon Investigational Site

Lyon, 69347, 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

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

Munich, 81377, Germany

Location

Lexicon Investigational Site

Neuss, 41464, Germany

Location

Lexicon Investigational Site

Jerusalem, 91120, Israel

Location

Lexicon Investigational Site

Amsterdam, North Holland, 1066X, Netherlands

Location

Lexicon Investigational Site

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Lexicon Investigational Site

Noord Brahant, 5631BM, Netherlands

Location

Lexicon Investigative Site

Rotterdam, 3015 CE, 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

Uppsala, 75185, Sweden

Location

Lexicon Investigational Site

Basingstoke Hampshire, RG249NA, United Kingdom

Location

Lexicon Investigational Site

Coventry, CV22DX, United Kingdom

Location

Lexicon Investigational Site

London, NW3 2QG, 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 (3)

• 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

• 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

• 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.

  PMID: 29330194 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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2014
• First Posted: February 14, 2014
• Study Start: March 11, 2014
• Primary Completion: March 29, 2016
• Study Completion: March 29, 2016
• Last Updated: February 26, 2018
• Results First Posted: September 25, 2017

Record last verified: 2018-01

Locations

SE (1); GB (7); AU (4); CA (2); BE (3); DE (9); NL (4); IL (1); FR (6); US (8); ES (5)