Clinical trial NCT01677910: TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoid Syndrome
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2012-09-03
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks
timeFrame: Baseline and 12 Weeks
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period
timeFrame: 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)
measure: Number of Participants With TEAEs in the Open-Label Extension Period
timeFrame: 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:
measure: Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels
timeFrame: Baseline and Week 12
measure: Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points
timeFrame: Baseline and 12 Weeks
measure: Change From Baseline in Abdominal Pain Averaged Across All Time-Points
timeFrame: Baseline and 12 Weeks
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Lexicon Investigational Site
state: Alabama
city: Palo Alto
country: United States
facility: Lexicon Investigational Site
state: California
city: San Francisco
country: United States
facility: Lexicon Investigational Site
state: California
city: Orlando
country: United States
facility: Lexicon Investigational Site
state: Florida
city: Iowa City
country: United States
facility: Lexicon Investigational Site
state: Iowa
city: Lexington
country: United States
facility: Lexicon Investigational Site
state: Kentucky
city: Kenner
country: United States
facility: Lexicon Investigational Site
state: Louisiana
city: Boston
country: United States
facility: Lexicon Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Lexicon Investigational Site
state: Massachusetts
city: Omaha
country: United States
facility: Lexicon Investigational Site
state: Nebraska
city: Buffalo
country: United States
facility: Lexicon Investigational Site
state: New York
city: New York
country: United States
facility: Lexicon Investigational Site
state: New York
city: Durham
country: United States
facility: Lexicon Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: Lexicon Investigational Site
state: Pennsylvania
city: Fort Worth
country: United States
facility: Lexicon Investigational Site
state: Texas
city: Houston
country: United States
facility: Lexicon Investigational Site
state: Texas
city: McAllen
country: United States
facility: Lexicon Investigational Site
state: Texas
city: Kogara
country: Australia
facility: Lexicon Investigational Site
state: New South Wales
city: Saint Leanoards
country: Australia
facility: Lexicon Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: Lexicon Investigational Site
state: Queensland
city: Fitzroy
country: Australia
facility: Lexicon Investigational Site
state: Victoria
city: Freemantle
country: Australia
facility: Lexicon Investigational Site
state: Western Australia
city: Woodville South
country: Australia
facility: Lexicon Investigational Site
city: Edegem
country: Belgium
facility: Lexicon Investigational Site
city: Gent
country: Belgium
facility: Lexicon Investigational Site
city: Yvoir
country: Belgium
facility: Lexicon Investigational Site
city: Calgary
country: Canada
facility: Lexicon Investigational Site
state: Alberta
city: Halifax
country: Canada
facility: Lexicon Investigational Site
state: Nova Scotia
city: Clichy
country: France
facility: Lexicon Investigational Site
city: Lille
country: France
facility: Lexicon Investigational Site
city: Lyon
country: France
facility: Lexicon Investigational Site
city: Marseille
country: France
facility: Lexicon Investigational Site
city: Strasbourg
country: France
facility: Lexicon Investigational Site
city: Villejuif
country: France
facility: Lexicon Investigational Site
city: Bad Berka
country: Germany
facility: Lexicon Investigational Site
city: Berlin
country: Germany
facility: Lexicon Investigational Site
city: Essen
country: Germany
facility: Lexicon Investigational Site
city: Hamburg
country: Germany
facility: Lexicon Investigational Site
city: Heidelberg
country: Germany
facility: Lexicon Investigational Site
city: Lubeck
country: Germany
facility: Lexicon Investigational Site
city: Mainz
country: Germany
facility: Lexicon Investigational Site
city: Marburg
country: Germany
facility: Lexicon Investigational Site
city: Munchen
country: Germany
facility: Lexicon Investigational Site
city: Neuss
country: Germany
facility: Lexicon Investigational Site
city: Jerusalem
country: Israel
facility: Lexicon Invetigational Site
city: Bologna
country: Italy
facility: Lexicon Investigational Site
city: Ferrara
country: Italy
facility: Lexicon Investigational Site
city: Milan
country: Italy
facility: Lexicon Investigational Site
city: Milan
country: Italy
facility: Lexicon Investigational Site
city: Modena
country: Italy
facility: Lexicon Investigational Site
city: Napoli
country: Italy
facility: Lexicon Investigational Site
city: Orbassano
country: Italy
facility: Lexicon Investigational Site
city: Perugia
country: Italy
facility: Lexicon Investigational Site
city: Pisa
country: Italy
facility: Lexicon Investigational Site
city: Rome
country: Italy
facility: Lexicon Investigational Site
city: Amsterdam
country: Netherlands
facility: Lexicon Investigational Site
city: Noord-Brahant
country: Netherlands
facility: Lexicon Investigational Site
city: Noord-Holland
country: Netherlands
facility: Lexicon Investigational Site
city: Zuid-Holland
country: Netherlands
facility: Lexicon Investigational Site
city: Barcelona
country: Spain
facility: Lexicon Investigational Site
city: Barcelona
country: Spain
facility: Lexicon Investigational Site
city: Madrid
country: Spain
facility: Lexicon Investigational Site
city: Madrid
country: Spain
facility: Lexicon Investigational Site
city: Seville
country: Spain
facility: Lexicon Investigational Site
city: Lund
country: Sweden
facility: Lexicon Investigational Site
city: Uppsala
country: Sweden
facility: Lexicon Investigational Site
city: Basingstoke-Hampshire
country: United Kingdom
facility: Lexicon Investigational Site
city: Coventry
country: United Kingdom
facility: Lexicon Investigational Site
city: Glasgow
country: United Kingdom
facility: Lexicon Investigational Site
city: Headington-Oxford
country: United Kingdom
facility: Lexicon Investigational Site
city: London
country: United Kingdom
facility: Lexicon Investigational Site
city: London
country: United Kingdom
facility: Lexicon Investigational Site
city: London
country: United Kingdom
facility: Lexicon Investigational Site
city: Manchester
country: United Kingdom
facility: Lexicon Investigational Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Lexicon Investigational Site
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc
name: Pablo Lapuerta, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.