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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

NCTNCT00853047 (opens ClinicalTrials.gov in a new tab)Other idLX1606.1-202-CSOther idLX1606.202
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Overview

Status
Completed
Phase
Phase 2
Enrollment
23 participants (actual)
Sponsor
Lexicon Pharmaceuticals · Industry
Design
Randomized · Triple masking
Countries
1 country

United States

Start
Mar 2009
Primary completion
Jun 2014
Completion
Jun 2014
First posted
27 Feb 2009 (estimated)
Last update posted
26 Dec 2018
Conditions
Carcinoid Syndrome

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2009201020112012201320142015
  1. Ph 2

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

    NCT00853047

    Mar 2009 to Jun 2014

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Telotristat etiprateDrug
  • Octreotide LAR DepotDrug
  • PlaceboDrug

Arms6

  • Experimental

    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.

  • Experimental

    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.

  • Experimental

    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.

  • Experimental

    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.

  • Experimental

    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.

  • Experimental

    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).

Primary outcomes2

Outcomes the sponsor listed as primary.

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

    Time frame · Up to 4 Weeks Core Phase

    Registry description

    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.

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

    Time frame · Up to 180 weeks in the open-label extension phase

    Registry description

    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.

Secondary outcomes(11)

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

    Time frame · Baseline to Week 4

    Registry description

    Participants recorded the number of BMs per day in a daily diary. The total number of BMs per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.

  2. Change From Baseline in Weekly Mean Stool Form

    Time frame · Baseline to Week 4

    Registry description

    Participants recorded stool form in a daily diary using a 6-point scale (0-none,1-hard, 2-firm, 3-soft, 4-loose, 5-watery). A negative change from Baseline indicates improvement.

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

    Time frame · Baseline to Week 4

    Registry description

    Participants recorded the sensation of urgency to defecate (Yes or No) in a daily diary. A negative change from Baseline indicates improvement.

  4. Change From Baseline in Number of Cutaneous Flushing Episodes

    Time frame · Baseline to Week 4

    Registry description

    Participants recorded the number of daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.

  5. Change From Baseline in Severity of Abdominal Pain or Discomfort

    Time frame · Baseline to Week 4

    Registry description

    Participants recorded the severity of abdominal pain or discomfort in a daily diary assessed using a 4-point scale (0-none, 1-mild, 2-moderate, 3-severe). A negative change from Baseline indicates improvement.

  6. Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)

    Time frame · Baseline to Week 4

    Registry description

    u5-HIAA is a standard test used in clinical practice to assess the neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. A negative change from Baseline indicates improvement.

  7. Change From Baseline in Chromogranin A

    Time frame · Baseline to Week 4

    Registry description

    Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.

  8. Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome

    Time frame · Week 4

    Registry description

    Participants were asked to answer the following question: "In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain, or discomfort?". The number of participants who answered Yes are reported.

  9. Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day

    Time frame · Baseline to Week 4

    Registry description

    Participants recorded details (location and frequency of injection) of subcutaneous injections of rescue, short-acting octreotide, if taken, in the daily diary. A negative change from Baseline indicates improvement.

  10. Time to First Rescue, Short-acting Octreotide

    Time frame · Baseline to Week 4

    Registry description

    Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.

  11. Number of Participants Experiencing Complete Response at Week 4

    Time frame · Baseline to Week 4

    Registry description

    Complete Response to treatment was defined as one of the following: 1. Less than 4 bowel movements per day; or 2. A decrease in daily bowel movements that is ≥ 50% from baseline; or 3. A positive response to the global assessment question ("In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain or discomfort?") for each of the last 2 weeks of the Treatment Period.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· Up to 4 Weeks Core Phase

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

GroupValue (Participants)
Placebo Core Phase4
Telotristat Etiprate 150 mg Core Phase3
Telotristat Etiprate 250 mg Core Phase3
Telotristat Etiprate 350 mg Core Phase2
Telotristat Etiprate 500 mg Core Phase9
Primary outcomeCount of participants· Up to 180 weeks in the open-label extension phase

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

GroupValue (Participants)
Telotristat Etiprate Open-Label Extension Phase18
Secondary and other outcome results(6)
Secondary outcomeMean· Baseline to Week 4

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

GroupValue (bowel movements/day)Spread
Placebo Core Phase0.820.435
Telotristat Etiprate 150 mg Core Phase-1.371.514
Telotristat Etiprate 250 mg Core Phase-2.172.259
Telotristat Etiprate 350 mg Core Phase-0.200
Telotristat Etiprate 500 mg Core Phase-0.712.048
Secondary outcomeMean· Baseline to Week 4

Change From Baseline in Weekly Mean Stool Form

GroupValue (units on a scale)Spread
Placebo Core Phase-0.070.222
Telotristat Etiprate 150 mg Core Phase-0.500.755
Telotristat Etiprate 250 mg Core Phase0.000.141
Telotristat Etiprate 350 mg Core Phase0.000
Telotristat Etiprate 500 mg Core Phase-0.170.579
Secondary outcomeMean· Baseline to Week 4

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

GroupValue (percentage of days)Spread
Placebo Core Phase-2.725.164
Telotristat Etiprate 150 mg Core Phase-34.4347.261
Telotristat Etiprate 250 mg Core Phase-32.1328.328
Telotristat Etiprate 350 mg Core Phase0.000
Telotristat Etiprate 500 mg Core Phase-8.4915.742
Secondary outcomeMean· Baseline to Week 4

Change From Baseline in Number of Cutaneous Flushing Episodes

GroupValue (cutaneous flushing episodes)Spread
Placebo Core Phase-0.430.435
Telotristat Etiprate 150 mg Core Phase-0.601.044
Telotristat Etiprate 250 mg Core Phase-0.300.436
Telotristat Etiprate 350 mg Core Phase-0.100
Telotristat Etiprate 500 mg Core Phase-0.030.673
Secondary outcomeMean· Baseline to Week 4

Change From Baseline in Severity of Abdominal Pain or Discomfort

GroupValue (units on a scale)Spread
Placebo Core Phase0.040.358
Telotristat Etiprate 150 mg Core Phase0.030.586
Telotristat Etiprate 250 mg Core Phase-0.530.808
Telotristat Etiprate 350 mg Core Phase0.030.153
Telotristat Etiprate 500 mg Core Phase0.160.358
Secondary outcomeMean· Baseline to Week 4

Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)

GroupValue (mg/24 hours)Spread
Placebo Core Phase-20.7317.212
Telotristat Etiprate 150 mg Core Phase-27.5545.891
Telotristat Etiprate 250 mg Core Phase-0.670.493
Telotristat Etiprate 350 mg Core Phase13.6019.092
Telotristat Etiprate 500 mg Core Phase-35.4949.949

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Placebo Core PhaseParticipants received placebo-matching telotristat etiprate capsules, 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 receive telotristat etiprate in the optional open-label extension period.0 / 50 / 54 / 5
Telotristat Etiprate 150 mg Core PhaseParticipants received telotristat etiprate capsules,150 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.0 / 30 / 33 / 3
Telotristat Etiprate 250 mg Core PhaseParticipants received 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.0 / 30 / 33 / 3
Telotristat Etiprate 350 mg Core PhaseParticipants received 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.0 / 31 / 32 / 3
Telotristat Etiprate 500 mg Core PhaseParticipants received 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.0 / 90 / 99 / 9
Telotristat Etiprate Open-Label Extension PhaseParticipants received 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).1 / 198 / 1918 / 19

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

Studies with results

0 studies on this page

Indexing hint: Randomized controlled trial · 2014

Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide.

Kulke et al. 2014Endocrine-related cancercited by 100

PMID 25012985PMC4295770DOI 10.1530/erc-14-0173PUB-25012985

Rights unknown
Source link

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedGelhorn 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

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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