Carcinoid SyndromePhase 2NCT01104415
Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome
A Phase 2 study testing Telotristat etiprate in people with Carcinoid Syndrome, run by Lexicon Pharmaceuticals at 10 sites in 2 countries.
Trial summary
The purpose of the study is to evaluate the safety and tolerability of orally administered telotristat etiprate (LX1606) in participants with symptomatic carcinoid syndrome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoid Syndrome
- What is being tested?
- Telotristat etiprate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 15 Jun 2010to 12 Feb 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Symptomatic carcinoid syndrome (≥4 bowel movements per day)
- Ability to provide written informed consent
Who cannot join
- ≥ 12 high-volume, watery bowel movements per day
- 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
- Administration of any investigational drug within 30 days of screening or any therapeutic protein or antibody within 90 days of screening
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
Germany6 sites
Lexicon Investigational Site
Bad Berka
Lexicon Investigational Site
Berlin
Lexicon Investigational Site
Halle
Lexicon Investigational Site
Lübeck
Lexicon Investigational Site
Marburg
Lexicon Investigational Site
Munich
United Kingdom4 sites
Lexicon Investigational Site
Basingstoke
Lexicon Investigational Site
Cambridge
Lexicon Investigational Site
London
Lexicon Investigational Site
Manchester
About this study
Official title: A Phase 2, Open-Label, Multi-Center, Serial Ascending-Dose, Dose-Finding Study to Evaluate the Safety and Tolerability of LX1606 in Subjects With Symptomatic Carcinoid Syndrome
The purpose of the study is to evaluate the safety and tolerability of orally administered telotristat etiprate (LX1606) in participants with symptomatic carcinoid syndrome.
- Conditions
- Carcinoid Syndrome
- Being tested
- Telotristat etiprate
- Medical subject headings
- Serotonin Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Telotristat etiprateDrug
Also called LX1606 Hippurate
Telotristat etiprate capsules orally three times daily.
| Study group | Role | What they receive |
|---|---|---|
| Telotristat etiprate - Core Phase | Experimental | Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period. Receives: Drug: Telotristat etiprate |
| Telotristat etiprate - Extension Period | Experimental | Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit. Receives: Drug: Telotristat etiprate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs 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. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.
Measured: Baseline up to Week 12 in the Core Phase
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period
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. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.
Measured: Up to 124 Weeks in the Extension Period
Secondary outcomes (9)
Change From Baseline in Number of Bowel Movements (BMs)
Participants recorded the number of bowel movements in a daily diary. The change from baseline value was calculated as the difference between mean numbers of BMs of the post-baseline interval (Weeks 9 to 12) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Measured: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Stool Form/Consistency
Participants assessed stool form/consistency in a daily diary using a 6-point scale (0-none, 1-hard, 2-firm, 3-soft, 4-loose, 5-watery). The change from the baseline value was calculated as the difference between a mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score and 5 indicates the worst score. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Measured: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Percentage of Days With Sensation of Urgency to Defecate
Participants assessed the urgency to defecate using a daily diary response to the following question, "Have you felt or experienced a sense of urgency to pass stool today?". The change from the baseline value was calculated as the difference between the mean score (percentage of days) of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Measured: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)
Sensation/severity of nausea was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of nausea experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Measured: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome
Participants assessed their symptoms using a weekly subjective response to 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 values for improvement in global assessment of symptoms associated with carcinoid syndrome in the Core Phase were averaged from Weeks 9 to 12.
Measured: Core Phase: Weeks 9-12; Extension Period: Week 24
Change From Baseline in Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)
The severity of abdominal pain was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of abdominal pain or experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicate the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Measured: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Daily Number of Cutaneous Flushing Episodes
Participants recorded the number of daily cutaneous flushing episodes experienced in the daily diary. The change from baseline value was calculated as the difference between the mean numbers of cutaneous flushing episodes of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Measured: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase
Clinically meaningful symptom reduction was defined as either: a) an average of < 4 bowel movements per day over 15 consecutive days, b) a 50% reduction from baseline in the number of bowel movements, c) a positive response to the question regarding adequate relief, or d) a 50% reduction from baseline in the number of daily flushing episodes.
Measured: Baseline to Week 12
Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels
Urinary 5-HIAA (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. The change from baseline value for the Extension Period was calculated as the difference between mean change in 5-HIAA of the post-baseline interval (Weeks 20 to 21) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.
Measured: Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2010 (estimated)
- Study start15 Jun 2010
- Primary completion12 Feb 2014
- Study completion12 Feb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoid SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lexicon Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pablo LaPuerta, MD, Study director, Lexicon Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01104415
- Sponsor's protocol ID
- LX1606.1-203-CS
- Other IDs
- LX1606.203, LX1032, 2009-016973-13, 2009
- Status last verified
- Feb 2019
- First submitted
- 12 Apr 2010
- Last updated
- 15 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Pavel M, Horsch D, Caplin M, Ramage J, Seufferlein T, Valle J, Banks P, Lapuerta P, Sands A, Zambrowicz B, Fleming D, Wiedenmann B. Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1511-9. doi: 10.1210/jc.2014-2247. Epub 2015 Jan 30.
PubMed 25636046
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-Label, Multi-Center, Serial Ascending-Dose, Dose-Finding Study to Evaluate the Safety and Tolerability of LX1606 in Subjects With Symptomatic Carcinoid Syndrome
- ClinicalTrials.gov ID
- NCT01104415
- Acronym / sponsor ID
- LX1606.1-203-CS
- Conditions
- Carcinoid Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Lexicon PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Jun 2010 (actual)
- Primary completion
- 12 Feb 2014 (actual)
- Study completion
- 12 Feb 2014 (actual)
- First posted
- 15 Apr 2010 (estimated)
- Results
- Posted 6 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate the safety and tolerability of orally administered telotristat etiprate (LX1606) in participants with symptomatic carcinoid syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Telotristat etiprate - Core Phase | Experimental | Drug: Telotristat etiprateFollowing a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period. |
| Telotristat etiprate - Extension Period | Experimental | Drug: Telotristat etiprateParticipants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
- Symptomatic carcinoid syndrome (≥4 bowel movements per day)
- Ability to provide written informed consent
Key exclusion criteria (8 listed)
- ≥ 12 high-volume, watery bowel movements per day
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Telotristat etiprateAlso: LX1606 HippurateTelotristat etiprate capsules orally three times daily. | Drug | Telotristat etiprate - Core Phase, Telotristat etiprate - Extension Period |
Primary outcome
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase
Time frame: Baseline up to Week 12 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. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period
Time frame: Up to 124 Weeks in the Extension Period
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. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.
9 secondary outcomes
Change From Baseline in Number of Bowel Movements (BMs)
Time frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Stool Form/Consistency
Time frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Percentage of Days With Sensation of Urgency to Defecate
Time frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)
Time frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome
Time frame: Core Phase: Weeks 9-12; Extension Period: Week 24
Change From Baseline in Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)
Time frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Change From Baseline in Daily Number of Cutaneous Flushing Episodes
Time frame: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24
Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase
Time frame: Baseline to Week 12
Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels
Time frame: Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25636046Pavel M, Horsch D, Caplin M, Ramage J, Seufferlein T, Valle J, Banks P, Lapuerta P, Sands A, Zambrowicz B, Fleming D, Wiedenmann B. Telotristat etiprate for carcinoid syndrome: a single-arm, multicenter trial. J Clin Endocrinol Metab. 2015 Apr;100(4):1511-9. doi: 10.1210/jc.2014-2247. Epub 2015 Jan 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pablo LaPuerta, MD study director
Lexicon Pharmaceuticals, Inc.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Telotristat etiprate in people with Carcinoid Syndrome, run by Lexicon Pharmaceuticals at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase (time frame: Baseline up to Week 12 in the Core Phase). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01104415, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2019.