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

NCT00853047 | Completed Phase 2 Results

• 2 other identifiers: LX1606.1-202-CSLX1606.202
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Carcinoid Syndrome

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase

  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.

  Up to 4 Weeks Core Phase

• Number of Participants With Any TEAE in the Open-Label Extension Phase

  An 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 receiving treatment.

  Up to 180 weeks in the open-label extension phase

Secondary Outcomes (11)

• Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day

  Baseline to Week 4

• Change From Baseline in Weekly Mean Stool Form

  Baseline to Week 4

• Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate

  Baseline to Week 4

• Change From Baseline in Number of Cutaneous Flushing Episodes

  Baseline to Week 4

• Change From Baseline in Severity of Abdominal Pain or Discomfort

  Baseline to Week 4

Study Arms (6)

Telotristat Etiprate 150 mg Core Phase

EXPERIMENTAL

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.

Drug: Telotristat etiprate; Drug: Octreotide LAR Depot

Telotristat Etiprate 250 mg Core Phase

EXPERIMENTAL

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.

Drug: Telotristat etiprate; Drug: Octreotide LAR Depot

Telotristat Etiprate 350 mg Core Phase

EXPERIMENTAL

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.

Drug: Telotristat etiprate; Drug: Octreotide LAR Depot

Telotristat Etiprate 500 mg Core Phase

EXPERIMENTAL

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.

Drug: Telotristat etiprate; Drug: Octreotide LAR Depot

Placebo Core Phase

EXPERIMENTAL

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.

Drug: Octreotide LAR Depot; Drug: Placebo

Telotristat Etiprate Open-Label Extension Phase

EXPERIMENTAL

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).

Drug: Telotristat etiprate; Drug: Octreotide LAR Depot

Interventions

Telotristat etiprate DRUG

Telotristat etiprate capsules; orally 3 times daily.

Also known as: LX1606

Telotristat Etiprate 150 mg Core Phase; Telotristat Etiprate 250 mg Core Phase; Telotristat Etiprate 350 mg Core Phase; Telotristat Etiprate 500 mg Core Phase; Telotristat Etiprate Open-Label Extension Phase

Octreotide LAR Depot DRUG

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

Placebo Core Phase; Telotristat Etiprate 150 mg Core Phase; Telotristat Etiprate 250 mg Core Phase; Telotristat Etiprate 350 mg Core Phase; Telotristat Etiprate 500 mg Core Phase; Telotristat Etiprate Open-Label Extension Phase

Placebo DRUG

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

Placebo Core Phase

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• ≥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

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead

Study Sites (9)

Hematology Oncology Services of Arkansas

Little Rock, Arkansas, 72205, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

St. Francis Medical Group Oncology and Hematology Specialists

Indianapolis, Indiana, 46237, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

Location

UT M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Oncology - McAllen

McAllen, Texas, 78503, United States

Location

Texas Oncology - Weslaco

Weslaco, Texas, 78596, United States

Location

Related Publications (2)

• 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.

  PMID: 27041406 DERIVED

• 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.

  PMID: 25012985 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 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2009
• First Posted: February 27, 2009
• Study Start: March 1, 2009
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: December 26, 2018
• Results First Posted: December 26, 2018

Record last verified: 2018-10

Locations

US (9)