Clinical trial NCT00853047: Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Ascending, Multidose Study To Determine Safety and Tolerability of Orally Administered LX1606 in Subjects With Symptomatic Carcinoid Syndrome Refractory to Stable-Dose Octreotide Long-Acting Release Depot Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoid Syndrome
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2009-02-27
Enrollment: 23
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 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase
timeFrame: Up to 4 Weeks Core Phase
measure: Number of Participants With Any TEAE in the Open-Label Extension Phase
timeFrame: Up to 180 weeks in the open-label extension phase
Secondary outcomes:
measure: Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day
timeFrame: Baseline to Week 4
measure: Change From Baseline in Weekly Mean Stool Form
timeFrame: Baseline to Week 4
measure: Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate
timeFrame: Baseline to Week 4
measure: Change From Baseline in Number of Cutaneous Flushing Episodes
timeFrame: Baseline to Week 4
measure: Change From Baseline in Severity of Abdominal Pain or Discomfort
timeFrame: Baseline to Week 4
measure: Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)
timeFrame: Baseline to Week 4
measure: Change From Baseline in Chromogranin A
timeFrame: Baseline to Week 4
measure: Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome
timeFrame: Week 4
measure: Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day
timeFrame: Baseline to Week 4
measure: Time to First Rescue, Short-acting Octreotide
timeFrame: Baseline to Week 4
measure: Number of Participants Experiencing Complete Response at Week 4
timeFrame: Baseline to Week 4
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Hematology Oncology Services of Arkansas
state: Arkansas
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Indianapolis
country: United States
facility: St. Francis Medical Group Oncology and Hematology Specialists
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Houston
country: United States
facility: UT M.D. Anderson Cancer Center
state: Texas
city: McAllen
country: United States
facility: Texas Oncology - McAllen
state: Texas
city: Weslaco
country: United States
facility: Texas Oncology - Weslaco
state: Texas
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Pablo Lapuerta, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.