Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy

NCT ID: NCT00853047

Last Updated: 2018-12-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2014-06-30

Brief Summary

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The purpose of this study is to evaluate the safety and tolerability of telotristat etiprate (LX1606) versus a placebo control in participants with symptomatic carcinoid syndrome not managed by stable-dose long-acting octreotide therapy. Following determination of the maximally tolerated or effective dose, cohort expansion will occur to confirm effect on symptoms and safety profile.

Detailed Description

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Conditions

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Carcinoid Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Telotristat Etiprate 150 mg Core Phase

Telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Group Type EXPERIMENTAL

Telotristat etiprate

Intervention Type DRUG

Telotristat etiprate capsules; orally 3 times daily.

Octreotide LAR Depot

Intervention Type DRUG

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Telotristat Etiprate 250 mg Core Phase

Telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Group Type EXPERIMENTAL

Telotristat etiprate

Intervention Type DRUG

Telotristat etiprate capsules; orally 3 times daily.

Octreotide LAR Depot

Intervention Type DRUG

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Telotristat Etiprate 350 mg Core Phase

Telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Group Type EXPERIMENTAL

Telotristat etiprate

Intervention Type DRUG

Telotristat etiprate capsules; orally 3 times daily.

Octreotide LAR Depot

Intervention Type DRUG

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Telotristat Etiprate 500 mg Core Phase

Telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.

Group Type EXPERIMENTAL

Telotristat etiprate

Intervention Type DRUG

Telotristat etiprate capsules; orally 3 times daily.

Octreotide LAR Depot

Intervention Type DRUG

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Placebo Core Phase

Placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.

Group Type EXPERIMENTAL

Octreotide LAR Depot

Intervention Type DRUG

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Placebo

Intervention Type DRUG

Placebo-matching telotristat etiprate capsules; orally 3 times daily.

Telotristat Etiprate Open-Label Extension Phase

Telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).

Group Type EXPERIMENTAL

Telotristat etiprate

Intervention Type DRUG

Telotristat etiprate capsules; orally 3 times daily.

Octreotide LAR Depot

Intervention Type DRUG

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Interventions

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Telotristat etiprate

Telotristat etiprate capsules; orally 3 times daily.

Intervention Type DRUG

Octreotide LAR Depot

A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.

Intervention Type DRUG

Placebo

Placebo-matching telotristat etiprate capsules; orally 3 times daily.

Intervention Type DRUG

Other Intervention Names

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LX1606

Eligibility Criteria

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Inclusion Criteria

* Males and females, aged 18 and older
* Biopsy-proven metastatic carcinoid tumor of the gastrointestinal (GI) tract with disease extent confirmed by computed tomography (CT), magnetic resonance imaging (MRI), or radionuclide imaging
* Symptoms not managed by stable-dose long-acting octreotide therapy (≥4 bowel movements per day)
* Ability to provide written informed consent

Exclusion Criteria

* ≥12 high volume, watery bowel movements per day associated with a clinical syndrome of volume contraction, dehydration, or hypotension compatible with a "pancreatic cholera"-type clinical syndrome
* Sponsor-unacceptable clinical laboratory values for hematology and liver function tests at screening
* Karnofsky status ≤70% - unable to care for self
* Surgery within 60 days prior to screening
* A history of short bowel syndrome
* Life expectancy \<12 months
* History of substance or alcohol abuse within 2 years prior to screening
* Previous exposure to a tryptophan hydroxylase (TPH) inhibitor
* Administration of any investigational drug within 30 days of screening or any therapeutic protein or antibody within 90 days of screening
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lexicon Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pablo Lapuerta, MD

Role: STUDY_DIRECTOR

Lexicon Pharmaceuticals, Inc.

Locations

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Hematology Oncology Services of Arkansas

Little Rock, Arkansas, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

St. Francis Medical Group Oncology and Hematology Specialists

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

UT M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Oncology - McAllen

McAllen, Texas, United States

Site Status

Texas Oncology - Weslaco

Weslaco, Texas, United States

Site Status

Countries

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United States

References

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Gelhorn HL, Kulke MH, O'Dorisio T, Yang QM, Jackson J, Jackson S, Boehm KA, Law L, Kostelec J, Auguste P, Lapuerta P. Patient-reported Symptom Experiences in Patients With Carcinoid Syndrome After Participation in a Study of Telotristat Etiprate: A Qualitative Interview Approach. Clin Ther. 2016 Apr;38(4):759-68. doi: 10.1016/j.clinthera.2016.03.002. Epub 2016 Mar 31.

Reference Type DERIVED
PMID: 27041406 (View on PubMed)

Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, Freiman J, Frazier K, Jackson J, Yao JC, Kvols L, Lapuerta P, Zambrowicz B, Fleming D, Sands A. Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide. Endocr Relat Cancer. 2014 Oct;21(5):705-14. doi: 10.1530/ERC-14-0173. Epub 2014 Jul 10.

Reference Type DERIVED
PMID: 25012985 (View on PubMed)

Other Identifiers

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LX1606.202

Identifier Type: OTHER

Identifier Source: secondary_id

LX1606.1-202-CS

Identifier Type: -

Identifier Source: org_study_id