Clinical trial NCT02063659: Telotristat Etiprate for Carcinoid Syndrome Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoid Syndrome
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-02-14
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
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 17.1 Weeks)
measure: Primary: Percent Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels
timeFrame: Baseline and 12 Weeks
measure: Number of Participants With Treatment-Emergent Adverse Events (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 52.6 Weeks)
Secondary outcomes:
measure: Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Stool Form/Consistency Averaged Across All Time-Points
timeFrame: Baseline and 12 Weeks
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
measure: Change in the Frequency of Rescue Short-acting, Somatostatin Analog (SSA) Used to Treat Carcinoid Syndrome Symptoms Averaged Across All Time-Points
timeFrame: Baseline and 12 weeks
measure: 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
timeFrame: Baseline and 12 Weeks
Other outcomes:
Locations:
city: Stanford
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: Boston
country: United States
facility: Lexicon Investigational Site
state: Massachusetts
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: Philadelphia
country: United States
facility: Lexicon Investigational Site
state: Pennsylvania
city: Kogara
country: Australia
facility: Lexicon Investigational Site
state: New South Wales
city: St. Leonards
country: Australia
facility: Lexicon Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: Lexicon Investigational Site
state: Queensland
city: East Melbourne
country: Australia
facility: Lexicon Investigational Site
state: Victoria
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: 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: Munich
country: Germany
facility: Lexicon Investigational Site
city: Neuss
country: Germany
facility: Lexicon Investigational Site
city: Jerusalem
country: Israel
facility: Lexicon Investigational Site
city: Amsterdam
country: Netherlands
facility: Lexicon Investigational Site
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Lexicon Investigational Site
state: Noord-Holland
city: Noord Brahant
country: Netherlands
facility: Lexicon Investigational Site
city: Rotterdam
country: Netherlands
facility: Lexicon Investigative 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: Sevilla
country: Spain
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: 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: 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: 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.