Carcinoid Syndrome
Conditions
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.
Interventions
Telotristat etiprate capsules; orally 3 times daily.
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
DRUGPlacebo
Placebo-matching telotristat etiprate capsules; orally 3 times daily.
Sponsors
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Up to 4 Weeks 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. |
| Number of Participants With Any TEAE in the Open-Label Extension Phase | Up to 180 weeks 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Mean Stool Form | Baseline to Week 4 | 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. |
| Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate | Baseline to Week 4 | Participants recorded the sensation of urgency to defecate (Yes or No) in a daily diary. A negative change from Baseline indicates improvement. |
| Change From Baseline in Number of Cutaneous Flushing Episodes | Baseline to Week 4 | 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. |
| Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) | Baseline to Week 4 | 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. |
| Change From Baseline in Severity of Abdominal Pain or Discomfort | Baseline to Week 4 | 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. |
| Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome | Week 4 | 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. |
| Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day | Baseline to Week 4 | 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. |
| Time to First Rescue, Short-acting Octreotide | Baseline to Week 4 | Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary. |
| Number of Participants Experiencing Complete Response at Week 4 | Baseline to Week 4 | 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. |
| Change From Baseline in Chromogranin A | Baseline to Week 4 | Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement. |
| Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day | Baseline to Week 4 | 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. |
Countries
United States
Participant flow
Recruitment details
A total of 23 participants were enrolled in the Core Phase (ie, Screening and Double-blind Treatment Period) from 11 sites, including 1 satellite site, in the United States. 19 participants entered the Open-label Extension Phase.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Core Phase Participants 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. | 5 |
| Telotristat Etiprate 150 mg Core Phase Participants 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. | 3 |
| Telotristat Etiprate 250 mg Core Phase Participants 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. | 3 |
| Telotristat Etiprate 350 mg Core Phase Participants 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. | 3 |
| Telotristat Etiprate 500 mg Core Phase Participants 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. | 9 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Core Phase | Participant Request | 0 | 0 | 0 | 1 | 0 | 0 |
| Open-Label Extension Phase | Investigator Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Open-Label Extension Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
| Open-Label Extension Phase | Participant Request | 0 | 0 | 0 | 0 | 0 | 7 |
| Open-Label Extension Phase | Reason Not Specified | 0 | 0 | 0 | 0 | 0 | 6 |
| Open-Label Extension Phase | Transfer to LX1606-302 | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo Core Phase | Total | Telotristat Etiprate 500 mg Core Phase | Telotristat Etiprate 350 mg Core Phase | Telotristat Etiprate 250 mg Core Phase | Telotristat Etiprate 150 mg Core Phase |
|---|---|---|---|---|---|---|
| Age, Continuous | 62.4 years STANDARD_DEVIATION 11.72 | 60.8 years STANDARD_DEVIATION 11.39 | 65.7 years STANDARD_DEVIATION 9.94 | 52.7 years STANDARD_DEVIATION 9.81 | 61.0 years STANDARD_DEVIATION 16.09 | 51.7 years STANDARD_DEVIATION 8.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 22 Participants | 9 Participants | 3 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 12 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 11 Participants | 5 Participants | 1 Participants | 2 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 9 | 1 / 19 |
| other Total, other adverse events | 4 / 5 | 3 / 3 | 3 / 3 | 2 / 3 | 9 / 9 | 18 / 19 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 9 | 8 / 19 |
Outcome results
Primary
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.
Time frame: Up to 180 weeks in the open-label extension phase
Population: The Safety Set Extension Period included all participants who received at least one dose of study drug in the open-label extensions phase.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Core Phase | Number of Participants With Any TEAE in the Open-Label Extension Phase | 18 Participants |
Primary
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.
Time frame: Up to 4 Weeks Core Phase
Population: The Safety Set Core Phase included all participants who received at least one dose of study drug in the core phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Any TEAE | 4 Participants |
| Placebo Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Related TEAEs | 3 Participants |
| Telotristat Etiprate 150 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Any TEAE | 3 Participants |
| Telotristat Etiprate 150 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Related TEAEs | 3 Participants |
| Telotristat Etiprate 250 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Any TEAE | 3 Participants |
| Telotristat Etiprate 250 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Related TEAEs | 0 Participants |
| Telotristat Etiprate 350 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Related TEAEs | 2 Participants |
| Telotristat Etiprate 350 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Any TEAE | 2 Participants |
| Telotristat Etiprate 500 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Any TEAE | 9 Participants |
| Telotristat Etiprate 500 mg Core Phase | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase | Related TEAEs | 6 Participants |
Secondary
Change From Baseline in Chromogranin A
Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.
Time frame: Baseline to Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Chromogranin A | -3251.2 ng/mL | Standard Deviation 7803.84 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Chromogranin A | -190.5 ng/mL | Standard Deviation 225.57 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Chromogranin A | -12.3 ng/mL | Standard Deviation 13.05 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Chromogranin A | 52.5 ng/mL | Standard Deviation 60.1 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Chromogranin A | 26011.4 ng/mL | Standard Deviation 59383.95 |
Secondary
Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day
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.
Time frame: Baseline to Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day | -0.38 injections per day | Standard Deviation 0.695 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day | -0.03 injections per day | Standard Deviation 0.058 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day | 0.03 injections per day | Standard Deviation 0.058 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day | 0.00 injections per day | Standard Deviation 0 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day | -0.29 injections per day | Standard Deviation 0.669 |
Secondary
Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day
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.
Time frame: Baseline to Week 4
Population: Participants from the modified Intent to Treat (mITT) Set, Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day | 0.82 bowel movements/day | Standard Deviation 0.435 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day | -1.37 bowel movements/day | Standard Deviation 1.514 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day | -2.17 bowel movements/day | Standard Deviation 2.259 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day | -0.20 bowel movements/day | Standard Deviation 0 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day | -0.71 bowel movements/day | Standard Deviation 2.048 |
Secondary
Change From Baseline in Number of Cutaneous Flushing Episodes
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.
Time frame: Baseline to Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Number of Cutaneous Flushing Episodes | -0.43 cutaneous flushing episodes | Standard Deviation 0.435 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Number of Cutaneous Flushing Episodes | -0.60 cutaneous flushing episodes | Standard Deviation 1.044 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Number of Cutaneous Flushing Episodes | -0.30 cutaneous flushing episodes | Standard Deviation 0.436 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Number of Cutaneous Flushing Episodes | -0.10 cutaneous flushing episodes | Standard Deviation 0 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Number of Cutaneous Flushing Episodes | -0.03 cutaneous flushing episodes | Standard Deviation 0.673 |
Secondary
Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate
Participants recorded the sensation of urgency to defecate (Yes or No) in a daily diary. A negative change from Baseline indicates improvement.
Time frame: Baseline to Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate | -2.72 percentage of days | Standard Deviation 5.164 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate | -34.43 percentage of days | Standard Deviation 47.261 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate | -32.13 percentage of days | Standard Deviation 28.328 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate | 0.00 percentage of days | Standard Deviation 0 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate | -8.49 percentage of days | Standard Deviation 15.742 |
Secondary
Change From Baseline in Severity of Abdominal Pain or Discomfort
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.
Time frame: Baseline to Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis. Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Severity of Abdominal Pain or Discomfort | 0.04 units on a scale | Standard Deviation 0.358 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Severity of Abdominal Pain or Discomfort | 0.03 units on a scale | Standard Deviation 0.586 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Severity of Abdominal Pain or Discomfort | -0.53 units on a scale | Standard Deviation 0.808 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Severity of Abdominal Pain or Discomfort | 0.03 units on a scale | Standard Deviation 0.153 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Severity of Abdominal Pain or Discomfort | 0.16 units on a scale | Standard Deviation 0.358 |
Secondary
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-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. A negative change from Baseline indicates improvement.
Time frame: Baseline to Week 4
Population: Participants from the Pharmacodynamic (PD) Analysis Set Core Phase, all participants who received any fraction of a dose of study drug and had a valid Baseline and at least 1 valid post-Baseline PD assessment, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) | -20.73 mg/24 hours | Standard Deviation 17.212 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) | -27.55 mg/24 hours | Standard Deviation 45.891 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) | -0.67 mg/24 hours | Standard Deviation 0.493 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) | 13.60 mg/24 hours | Standard Deviation 19.092 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) | -35.49 mg/24 hours | Standard Deviation 49.949 |
Secondary
Change From Baseline in Weekly Mean Stool Form
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.
Time frame: Baseline to Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Core Phase | Change From Baseline in Weekly Mean Stool Form | -0.07 units on a scale | Standard Deviation 0.222 |
| Telotristat Etiprate 150 mg Core Phase | Change From Baseline in Weekly Mean Stool Form | -0.50 units on a scale | Standard Deviation 0.755 |
| Telotristat Etiprate 250 mg Core Phase | Change From Baseline in Weekly Mean Stool Form | 0.00 units on a scale | Standard Deviation 0.141 |
| Telotristat Etiprate 350 mg Core Phase | Change From Baseline in Weekly Mean Stool Form | 0.00 units on a scale | Standard Deviation 0 |
| Telotristat Etiprate 500 mg Core Phase | Change From Baseline in Weekly Mean Stool Form | -0.17 units on a scale | Standard Deviation 0.579 |
Secondary
Number of Participants Experiencing Complete Response at Week 4
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.
Time frame: Baseline to Week 4
Population: The mITT Set Core Phase included all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Core Phase | Number of Participants Experiencing Complete Response at Week 4 | 0 Participants |
| Telotristat Etiprate 150 mg Core Phase | Number of Participants Experiencing Complete Response at Week 4 | 1 Participants |
| Telotristat Etiprate 250 mg Core Phase | Number of Participants Experiencing Complete Response at Week 4 | 2 Participants |
| Telotristat Etiprate 350 mg Core Phase | Number of Participants Experiencing Complete Response at Week 4 | 1 Participants |
| Telotristat Etiprate 500 mg Core Phase | Number of Participants Experiencing Complete Response at Week 4 | 2 Participants |
Secondary
Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome
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.
Time frame: Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Core Phase | Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome | 0 Participants |
| Telotristat Etiprate 150 mg Core Phase | Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome | 1 Participants |
| Telotristat Etiprate 250 mg Core Phase | Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome | 2 Participants |
| Telotristat Etiprate 350 mg Core Phase | Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome | 1 Participants |
| Telotristat Etiprate 500 mg Core Phase | Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome | 3 Participants |
Secondary
Time to First Rescue, Short-acting Octreotide
Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.
Time frame: Baseline to Week 4
Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, As per protocol only the Placebo Core Phase and Telotristat Etiprate 500 mg Core Phase were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo Core Phase | Time to First Rescue, Short-acting Octreotide | 1.00 days |
| Telotristat Etiprate 150 mg Core Phase | Time to First Rescue, Short-acting Octreotide | 1.00 days |