Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy
Sponsor
Lexicon Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00853047
Collaborator
(none)
23
9
6
63
2.6
0
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
23 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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 Start Date
:
Mar 1, 2009
Actual Primary Completion Date
:
Jun 1, 2014
Actual Study Completion Date
:
Jun 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
|
| 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. |
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
|
| 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. |
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
|
| 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. |
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
|
| 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. |
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
Drug: Placebo
Placebo-matching telotristat etiprate capsules; orally 3 times daily.
|
| 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). |
Drug: Telotristat etiprate
Telotristat etiprate capsules; orally 3 times daily.
Other Names:
Drug: Octreotide LAR Depot
A stable-dose octreotide LAR depot therapy; administered subcutaneously once per month.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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 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.
- 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 Chromogranin A [Baseline to Week 4]
Blood samples were collected for assessment of Chromogranin A level. 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hematology Oncology Services of Arkansas | Little Rock | Arkansas | United States | 72205 |
| 2 | UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | United States | 94115 |
| 3 | St. Francis Medical Group Oncology and Hematology Specialists | Indianapolis | Indiana | United States | 46237 |
| 4 | University of Iowa | Iowa City | Iowa | United States | 52242 |
| 5 | Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 6 | Nebraska Methodist Hospital | Omaha | Nebraska | United States | 68114 |
| 7 | UT M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 8 | Texas Oncology - McAllen | McAllen | Texas | United States | 78503 |
| 9 | Texas Oncology - Weslaco | Weslaco | Texas | United States | 78596 |
Sponsors and Collaborators
- Lexicon Pharmaceuticals
Investigators
- Study Director: Pablo Lapuerta, MD, Lexicon Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Lexicon Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00853047
Other Study ID Numbers:
- LX1606.1-202-CS
- LX1606.202
First Posted:
Feb 27, 2009
Last Update Posted:
Dec 26, 2018
Last Verified:
Oct 1, 2018
Additional relevant MeSH terms:
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | Participants 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). |
| Period Title: Core Phase | ||||||
| STARTED | 5 | 3 | 3 | 3 | 9 | 0 |
| COMPLETED | 5 | 3 | 3 | 2 | 9 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 0 | 0 |
| Period Title: Core Phase | ||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 19 |
| Completed 8-week Extension Period | 0 | 0 | 0 | 0 | 0 | 16 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 2 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 17 |
Baseline Characteristics
| Arm/Group Title | 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 | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 5 | 3 | 3 | 3 | 9 | 23 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
62.4
(11.72)
|
51.7
(8.08)
|
61.0
(16.09)
|
52.7
(9.81)
|
65.7
(9.94)
|
60.8
(11.39)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
2
40%
|
3
100%
|
1
33.3%
|
2
66.7%
|
4
44.4%
|
12
52.2%
|
| Male |
3
60%
|
0
0%
|
2
66.7%
|
1
33.3%
|
5
55.6%
|
11
47.8%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
4.3%
|
| White |
5
100%
|
2
66.7%
|
3
100%
|
3
100%
|
9
100%
|
22
95.7%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase |
|---|---|
| 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. |
| Time Frame | Up to 4 Weeks Core Phase |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Set Core Phase included all participants who received at least one dose of study drug in the core phase. |
| Arm/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 3 | 3 | 3 | 9 |
| Any TEAE |
4
80%
|
3
100%
|
3
100%
|
2
66.7%
|
9
100%
|
| Related TEAEs |
3
60%
|
3
100%
|
0
0%
|
2
66.7%
|
6
66.7%
|
| Title | Number of Participants With Any TEAE in the Open-Label Extension Phase |
|---|---|
| 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. |
| Time Frame | Up to 180 weeks in the open-label extension phase |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety Set Extension Period included all participants who received at least one dose of study drug in the open-label extensions phase. |
| Arm/Group Title | Telotristat Etiprate Open-Label Extension Phase |
|---|---|
| Arm/Group Description | Participants 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). |
| Measure Participants | 19 |
| Count of Participants [Participants] |
18
360%
|
| Title | Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day |
|---|---|
| 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. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 3 | 3 | 1 | 7 |
| Mean (Standard Deviation) [bowel movements/day] |
0.82
(0.435)
|
-1.37
(1.514)
|
-2.17
(2.259)
|
-0.20
(0)
|
-0.71
(2.048)
|
| Title | Change From Baseline in Weekly Mean Stool Form |
|---|---|
| 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. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 3 | 2 | 1 | 7 |
| Mean (Standard Deviation) [units on a scale] |
-0.07
(0.222)
|
-0.50
(0.755)
|
0.00
(0.141)
|
0.00
(0)
|
-0.17
(0.579)
|
| Title | Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 3 | 3 | 1 | 7 |
| Mean (Standard Deviation) [percentage of days] |
-2.72
(5.164)
|
-34.43
(47.261)
|
-32.13
(28.328)
|
0.00
(0)
|
-8.49
(15.742)
|
| Title | Change From Baseline in Number of Cutaneous Flushing Episodes |
|---|---|
| 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. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 3 | 3 | 1 | 7 |
| Mean (Standard Deviation) [cutaneous flushing episodes] |
-0.43
(0.435)
|
-0.60
(1.044)
|
-0.30
(0.436)
|
-0.10
(0)
|
-0.03
(0.673)
|
| Title | Change From Baseline in Severity of Abdominal Pain or Discomfort |
|---|---|
| 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. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 3 | 3 | 3 | 8 |
| Mean (Standard Deviation) [units on a scale] |
0.04
(0.358)
|
0.03
(0.586)
|
-0.53
(0.808)
|
0.03
(0.153)
|
0.16
(0.358)
|
| Title | Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) |
|---|---|
| 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. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 2 | 3 | 2 | 8 |
| Mean (Standard Deviation) [mg/24 hours] |
-20.73
(17.212)
|
-27.55
(45.891)
|
-0.67
(0.493)
|
13.60
(19.092)
|
-35.49
(49.949)
|
| Title | Change From Baseline in Chromogranin A |
|---|---|
| Description | Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 2 | 3 | 2 | 8 |
| Mean (Standard Deviation) [ng/mL] |
-3251.2
(7803.84)
|
-190.5
(225.57)
|
-12.3
(13.05)
|
52.5
(60.10)
|
26011.4
(59383.95)
|
| Title | Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome |
|---|---|
| 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. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 2 | 3 | 2 | 7 |
| Count of Participants [Participants] |
0
0%
|
1
33.3%
|
2
66.7%
|
1
33.3%
|
3
33.3%
|
| Title | Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day |
|---|---|
| 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. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 4 | 3 | 3 | 1 | 7 |
| Mean (Standard Deviation) [injections per day] |
-0.38
(0.695)
|
-0.03
(0.058)
|
0.03
(0.058)
|
0.00
(0)
|
-0.29
(0.669)
|
| Title | Time to First Rescue, Short-acting Octreotide |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo Core Phase | Telotristat Etiprate 500 mg Core Phase |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 5 | 9 |
| Median (95% Confidence Interval) [days] |
1.00
|
1.00
|
| Title | Number of Participants Experiencing Complete Response at Week 4 |
|---|---|
| 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. |
| Time Frame | Baseline to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 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 |
|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. |
| Measure Participants | 5 | 3 | 3 | 3 | 9 |
| Count of Participants [Participants] |
0
0%
|
1
33.3%
|
2
66.7%
|
1
33.3%
|
2
22.2%
|
Adverse Events
| Time Frame | Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Set included all participants who received at least one dose of study drug. | |||||||||||
| Arm/Group Title | 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 | ||||||
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | Participants 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). | ||||||
All Cause Mortality |
||||||||||||
| 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 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
Serious Adverse Events |
||||||||||||
| 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 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 8/19 (42.1%) | ||||||
| Cardiac disorders | ||||||||||||
| Angina pectoris | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Atrial fibrillation | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Pulmonary valve stenosis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Tricuspid valve incompetence | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Nausea | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Vomiting | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Intestinal perforation | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| General disorders | ||||||||||||
| Asthenia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Disease progression | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Cholecystitis acute | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Joint effusion | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Tumour pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Breast cancer | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Squamous cell carcinoma of skin | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Nervous system disorders | ||||||||||||
| Syncope | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Renal failure chronic | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Renal failure acute | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Surgical and medical procedures | ||||||||||||
| Mass excision | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Small intestinal resection | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Cholecystectomy | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Vascular disorders | ||||||||||||
| Hypertensive crisis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| 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 | |||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/5 (80%) | 3/3 (100%) | 3/3 (100%) | 2/3 (66.7%) | 9/9 (100%) | 18/19 (94.7%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Thrombocytopenia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Cardiac disorders | ||||||||||||
| Angina pectoris | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Cardiac failure congestive | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Palpitations | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Pulmonary valve incompetence | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Eye disorders | ||||||||||||
| Blepharitis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Keratoconjunctivitis sicca | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Photophobia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Vision blurred | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Visual impairment | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Diarrhoea | 2/5 (40%) | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 4/9 (44.4%) | 10/19 (52.6%) | ||||||
| Nausea | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/9 (44.4%) | 9/19 (47.4%) | ||||||
| Abdominal distension | 1/5 (20%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/9 (11.1%) | 3/19 (15.8%) | ||||||
| Abdominal Pain | 0/5 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/9 (11.1%) | 6/19 (31.6%) | ||||||
| Gastrooesophageal reflux disease | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 2/19 (10.5%) | ||||||
| Abdominal discomfort | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 4/19 (21.1%) | ||||||
| Abdominal pain lower | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Abdominal pain upper | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Dyspepsia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Rectal haemorrhage | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 3/19 (15.8%) | ||||||
| Vomiting | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 6/19 (31.6%) | ||||||
| Constipation | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/19 (5.3%) | ||||||
| Diverticulum intestinal | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Frequent bowel movements | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Haematochezia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Inguinal hernia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Intestinal ischaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Malabsorption | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Melaena | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Proctalgia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Retching | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Small intestinal obstruction | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Steatorrhoea | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Abdominal tenderness | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Epigastric discomfort | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Gastrointestinal hypermotility | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Haemorrhoids | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Toothache | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Faecal incontinence | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| General disorders | ||||||||||||
| Fatigue | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/9 (22.2%) | 7/19 (36.8%) | ||||||
| Early satiety | 0/5 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Chest pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 4/19 (21.1%) | ||||||
| Oedema peripheral | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Pyrexia | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Chest discomfort | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Chills | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Feeling cold | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Infusion site swelling | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Injection site haematoma | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Local swelling | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Nodule | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Feeling abnormal | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Asthenia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hepatobiliary disorders | ||||||||||||
| Hepatic pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Infections and infestations | ||||||||||||
| Bronchitis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Nasopharyngitis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Upper respiratory tract infection | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Urinary tract infection | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 3/19 (15.8%) | ||||||
| Urinary tract infection bacterial | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Pneumonia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Herpes zoster | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Cartilage injury | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Contusion | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Foot fracture | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Joint sprain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Investigations | ||||||||||||
| Weight decreased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 4/19 (21.1%) | ||||||
| Activated partial thromboplastin time prolonged | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Alanine aminotransferase increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Aspartate aminotransferase increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Blood bilirubin increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Blood cholesterol increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Cardiac murmur | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Gamma-glutamyltransferase increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Haemoglobin decreased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Weight increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Blood alkaline phophatase increased | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Blood glucose decreased | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Blood triglycerides increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Low density lipoprotein increased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Neutrophil count decreased | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Neutrophil count increased | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Protein total decreased | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Urine colour abnormal | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| White blood cell count increased | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Decreased appetite | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 4/19 (21.1%) | ||||||
| Hypokalemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 3/19 (15.8%) | ||||||
| Hypomagnesaemia | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 3/19 (15.8%) | ||||||
| Vitamin D deficiency | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Dehydration | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/19 (5.3%) | ||||||
| Failure to thrive | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Fluid overload | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Folate deficiency | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hyperglycaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hyperkalaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hypoalbuminaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/19 (5.3%) | ||||||
| Hypocalcaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hypophosphataemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Malnutrition | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Vitamin A deficiency | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Vitamin B12 deficiency | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Vitamin E deficiency | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Vitamin K deficiency | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hypercholesterolaemia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Hypoglycaemia | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Back pain | 1/5 (20%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/9 (22.2%) | 5/19 (26.3%) | ||||||
| Arthralgia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 3/19 (15.8%) | ||||||
| Arthritis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Flank pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Rheumatoid arthritis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Bone pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Bursitis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Muscle spasms | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Muscular weakness | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Musculoskeletal chest pain | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Myalgia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/19 (5.3%) | ||||||
| Pain in extremity | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Rotator cuff syndrome | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Musculoskeletal pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Dysgeusia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 0/19 (0%) | ||||||
| Dizziness | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Headache | 1/5 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 3/19 (15.8%) | ||||||
| Neuropathy peripheral | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Sinus headache | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Syncope | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Memory impairment | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Lethargy | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Psychiatric disorders | ||||||||||||
| Anxiety | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Insomnia | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Depression | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Mood altered | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Sleep disorder | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Dysuria | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Haematuria | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Hydronephrosis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Nephrolithiasis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Renal failure | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Urine abnormality | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Bilirubinuria | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Oliguria | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Proteinuria | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Urinary hesitation | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Reproductive system and breast disorders | ||||||||||||
| Prostatomegaly | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Scrotal pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Scrotal oedema | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Chronic obstructive pulmonary disease | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 2/19 (10.5%) | ||||||
| Dyspnoea | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Oropharyngeal pain | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Pleural effusion | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Productive cough | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Apnoea | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Atelectasis | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Bronchitis chronic | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Cough | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 1/19 (5.3%) | ||||||
| Hiccups | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Orthopnoea | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Pulmonary oedema | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Respiratory tract congestion | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Upper respiratory tract congestion | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Sinus congestion | 0/5 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Hyperhidrosis | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Dermatitis acneiform | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Erythema | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Night sweats | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Rash | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Skin discolouration | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Acne | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Dry Skin | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Rash erythematous | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/9 (11.1%) | 0/19 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Flushing | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/9 (22.2%) | 7/19 (36.8%) | ||||||
| Hypertension | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 2/19 (10.5%) | ||||||
| Hot flush | 0/5 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/9 (0%) | 1/19 (5.3%) | ||||||
| Peripheral coldness | 0/5 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/9 (0%) | 0/19 (0%) | ||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institution must provide any proposed publication or presentation to Sponsor for Sponsor's review, comment and approval at least thirty (30) days prior to the proposed submission for publication date or the proposed presentation date. Sponsor shall have the right to have deleted from the final version of the publication any confidential information, proprietary information, or patentable subject matter.
Results Point of Contact
| Name/Title | Pablo Lapuerta, MD |
|---|---|
| Organization | Lexicon Pharmaceuticals, Inc. |
| Phone | |
| plapuerta@lexpharma.com |
Responsible Party:
Lexicon Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00853047
Other Study ID Numbers:
- LX1606.1-202-CS
- LX1606.202
First Posted:
Feb 27, 2009
Last Update Posted:
Dec 26, 2018
Last Verified:
Oct 1, 2018