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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01677910




Registration number
NCT01677910
Ethics application status
Date submitted
30/08/2012
Date registered
3/09/2012
Date last updated
27/02/2018

Titles & IDs
Public title
TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome)
Scientific 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
Secondary ID [1] 0 0
LX1606.301
Secondary ID [2] 0 0
LX1606.1-301-CS
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoid Syndrome 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Telotristat etiprate
Treatment: Drugs - Placebo-matching telotristat etiprate

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.

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.

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.

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.


Treatment: Drugs: Telotristat etiprate
Telotristat etiprate tablets.

Treatment: Drugs: Placebo-matching telotristat etiprate
Placebo-matching telotristat etiprate tablets.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks
Timepoint [1] 0 0
Baseline and 12 Weeks
Primary outcome [2] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period
Timepoint [2] 0 0
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)
Primary outcome [3] 0 0
Number of Participants With TEAEs in the Open-Label Extension Period
Timepoint [3] 0 0
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 [1] 0 0
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [2] 0 0
Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points
Timepoint [2] 0 0
Baseline and 12 Weeks
Secondary outcome [3] 0 0
Change From Baseline in Abdominal Pain Averaged Across All Time-Points
Timepoint [3] 0 0
Baseline and 12 Weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/03/2016
Sample size
Target
Accrual to date
Final
135
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Lexicon Investigational Site - Kogara
Recruitment hospital [2] 0 0
Lexicon Investigational Site - Saint Leanoards
Recruitment hospital [3] 0 0
Lexicon Investigational Site - Herston
Recruitment hospital [4] 0 0
Lexicon Investigational Site - Fitzroy
Recruitment hospital [5] 0 0
Lexicon Investigational Site - Freemantle
Recruitment hospital [6] 0 0
Lexicon Investigational Site - Woodville South
Recruitment postcode(s) [1] 0 0
2217 - Kogara
Recruitment postcode(s) [2] 0 0
2065 - Saint Leanoards
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
6160 - Freemantle
Recruitment postcode(s) [6] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
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United States of America
State/province [3] 0 0
Florida
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United States of America
State/province [4] 0 0
Iowa
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United States of America
State/province [5] 0 0
Kentucky
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United States of America
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Louisiana
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United States of America
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Massachusetts
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United States of America
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Nebraska
Country [9] 0 0
United States of America
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New York
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United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
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United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Belgium
State/province [13] 0 0
Edegem
Country [14] 0 0
Belgium
State/province [14] 0 0
Gent
Country [15] 0 0
Belgium
State/province [15] 0 0
Yvoir
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
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Canada
State/province [17] 0 0
Nova Scotia
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France
State/province [18] 0 0
Clichy
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France
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Lille
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France
State/province [20] 0 0
Lyon
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France
State/province [21] 0 0
Marseille
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France
State/province [22] 0 0
Strasbourg
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France
State/province [23] 0 0
Villejuif
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Germany
State/province [24] 0 0
Bad Berka
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Germany
State/province [25] 0 0
Berlin
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Germany
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Essen
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
State/province [29] 0 0
Lubeck
Country [30] 0 0
Germany
State/province [30] 0 0
Mainz
Country [31] 0 0
Germany
State/province [31] 0 0
Marburg
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Germany
State/province [32] 0 0
Munchen
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Germany
State/province [33] 0 0
Neuss
Country [34] 0 0
Israel
State/province [34] 0 0
Jerusalem
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Italy
State/province [35] 0 0
Bologna
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Italy
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Ferrara
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Italy
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Milan
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Italy
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Modena
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Italy
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Napoli
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Italy
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Orbassano
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Italy
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Perugia
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Italy
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Pisa
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Italy
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Rome
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Netherlands
State/province [44] 0 0
Amsterdam
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Netherlands
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Noord-Brahant
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Netherlands
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Noord-Holland
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Netherlands
State/province [47] 0 0
Zuid-Holland
Country [48] 0 0
Spain
State/province [48] 0 0
Barcelona
Country [49] 0 0
Spain
State/province [49] 0 0
Madrid
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Spain
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Seville
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Sweden
State/province [51] 0 0
Lund
Country [52] 0 0
Sweden
State/province [52] 0 0
Uppsala
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United Kingdom
State/province [53] 0 0
Basingstoke-Hampshire
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Coventry
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Glasgow
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United Kingdom
State/province [56] 0 0
Headington-Oxford
Country [57] 0 0
United Kingdom
State/province [57] 0 0
London
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Manchester
Country [59] 0 0
United Kingdom
State/province [59] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Lexicon Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01677910
Trial related presentations / 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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Pablo Lapuerta, MD
Address 0 0
Lexicon Pharmaceuticals, Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01677910