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Trial record 39 of 40 for:    somatostatin analogues | Neuroendocrine Tumors

Telotristat Etiprate for Carcinoid Syndrome Therapy (TELECAST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02063659
Recruitment Status : Completed
First Posted : February 14, 2014
Results First Posted : September 25, 2017
Last Update Posted : February 26, 2018
Sponsor:
Information provided by (Responsible Party):
Lexicon Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Carcinoid Syndrome
Interventions Drug: Telotristat etiprate
Drug: Placebo
Enrollment 76
Recruitment Details Participants took part in the study at 31 investigative sites in Australia, Belgium, Canada, France, Germany, Israel, Netherlands, Spain, Sweden, United Kingdom, and the United States from 11 Mar 2014 to 29 Mar 2016.
Pre-assignment Details Participants with Carcinoid Syndrome not adequately controlled by somatostatin analog (SSA) therapy were randomly assigned in a 1:1:1 ratio to receive placebo, 250 mg or 500 mg telotristat etiprate (LX1606) in the double-blind treatment period and were eligible to receive 500 mg telotristat etiprate in the open-label extension period.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate Telotristat Etiprate Open-Label Extension
Hide Arm/Group Description Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period. Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period. Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period. Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.
Period Title: Double-Blind Treatment Period
Started 26 25 25 0
Completed 24 22 22 0
Not Completed 2 3 3 0
Reason Not Completed
Adverse Event             1             2             0             0
Physician Decision             1             0             0             0
Withdrawal of consent             0             1             3             0
Period Title: Open-Label Extension Period (OLE)
Started 0 0 0 67
Completed 0 0 0 47
Not Completed 0 0 0 20
Reason Not Completed
Physician Decision             0             0             0             1
Withdrawal of Consent             0             0             0             9
Lack of Efficacy             0             0             0             1
Adverse Event             0             0             0             7
Reason not Specified             0             0             0             2
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate Total
Hide Arm/Group Description Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period. Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period. Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period. Total of all reporting groups
Overall Number of Baseline Participants 26 25 25 76
Hide Baseline Analysis Population Description
Safety population included all participants who received at least one dose of study drug,
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 26 participants 25 participants 25 participants 76 participants
62.2  (10.32) 63.6  (12.62) 62.7  (11.97) 62.8  (11.52)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
< 65 years
12
  46.2%
14
  56.0%
15
  60.0%
41
  53.9%
≥ 65 years
14
  53.8%
11
  44.0%
10
  40.0%
35
  46.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
Female
13
  50.0%
11
  44.0%
10
  40.0%
34
  44.7%
Male
13
  50.0%
14
  56.0%
15
  60.0%
42
  55.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
25
  96.2%
25
 100.0%
25
 100.0%
75
  98.7%
Unknown or Not Reported
1
   3.8%
0
   0.0%
0
   0.0%
1
   1.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 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
   0.0%
0
   0.0%
1
   4.0%
1
   1.3%
White
25
  96.2%
25
 100.0%
23
  92.0%
73
  96.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   3.8%
0
   0.0%
1
   4.0%
2
   2.6%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
Canada
0
   0.0%
1
   4.0%
1
   4.0%
2
   2.6%
Sweden
0
   0.0%
2
   8.0%
0
   0.0%
2
   2.6%
Netherlands
3
  11.5%
2
   8.0%
1
   4.0%
6
   7.9%
Belgium
1
   3.8%
2
   8.0%
2
   8.0%
5
   6.6%
United States
4
  15.4%
5
  20.0%
7
  28.0%
16
  21.1%
United Kingdom
7
  26.9%
3
  12.0%
3
  12.0%
13
  17.1%
Israel
2
   7.7%
3
  12.0%
2
   8.0%
7
   9.2%
Australia
4
  15.4%
0
   0.0%
3
  12.0%
7
   9.2%
France
1
   3.8%
0
   0.0%
0
   0.0%
1
   1.3%
Germany
3
  11.5%
2
   8.0%
2
   8.0%
7
   9.2%
Spain
1
   3.8%
5
  20.0%
4
  16.0%
10
  13.2%
Somatostatin Analog (SSA) Therapy Schedule at Study Entry   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
3-Week
6
  23.1%
7
  28.0%
9
  36.0%
22
  28.9%
4-Week
20
  76.9%
15
  60.0%
11
  44.0%
46
  60.5%
Not on SSA
0
   0.0%
3
  12.0%
5
  20.0%
8
  10.5%
[1]
Measure Description: Patients who were on a 2-week SSA therapy or receiving SSA therapy via a subcutaneous continuous infusion pump are included in the "4-week" category.
SSA Therapy Name at Study Entry  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
Octreotide
12
  46.2%
17
  68.0%
16
  64.0%
45
  59.2%
Lanreotide
14
  53.8%
5
  20.0%
3
  12.0%
22
  28.9%
Unknown
0
   0.0%
0
   0.0%
1
   4.0%
1
   1.3%
Not Applicable
0
   0.0%
3
  12.0%
5
  20.0%
8
  10.5%
Childbearing Potential  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
Yes
2
   7.7%
4
  16.0%
1
   4.0%
7
   9.2%
No
11
  42.3%
7
  28.0%
9
  36.0%
27
  35.5%
Not Applicable
13
  50.0%
14
  56.0%
15
  60.0%
42
  55.3%
Urinary 5-Hydroxyindoleacetic acid (5-HIAA) at Randomization   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
≤ ULN
9
  34.6%
5
  20.0%
8
  32.0%
22
  28.9%
> ULN
17
  65.4%
18
  72.0%
17
  68.0%
52
  68.4%
Unknown
0
   0.0%
2
   8.0%
0
   0.0%
2
   2.6%
[1]
Measure Description: ULN=upper limit of normal.
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 26 participants 25 participants 25 participants 76 participants
North America
4
  15.4%
6
  24.0%
8
  32.0%
18
  23.7%
Europe
16
  61.5%
16
  64.0%
12
  48.0%
44
  57.9%
Rest of the World
6
  23.1%
3
  12.0%
5
  20.0%
14
  18.4%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 26 participants 25 participants 25 participants 76 participants
76.38  (16.959) 74.74  (17.839) 76.69  (26.188) 75.94  (20.442)
Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 26 participants 25 participants 25 participants 76 participants
169.48  (9.765) 169.74  (10.025) 170.08  (8.525) 169.76  (9.327)
Baseline Body Mass Index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 26 participants 25 participants 25 participants 76 participants
26.28  (4.364) 25.96  (5.258) 26.21  (9.213) 26.16  (6.521)
[1]
Measure Description: BMI was calculated by weight (kg) / (height [cm] × 0.01)^2.
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period
Hide 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 First dose of study drug to within 30 days of last dose of study drug in the Double-Blind Treatment Period (Up to 17.1 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all participants who received at least one dose of study drug, was used for analysis.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 26 25 25
Measure Type: Count of Participants
Unit of Measure: Participants
21
  80.8%
25
 100.0%
22
  88.0%
2.Primary Outcome
Title Primary: Percent Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels
Hide Description u5-HIAA is a standard test used in clinical practice to assess neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. A negative change from Baseline indicates improvement.
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants, with data available for this endpoint were included in the analysis.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 22 17 19
Mean (Standard Deviation)
Unit of Measure: percentage change of mg/24 hours
97.721  (397.0107) -33.164  (58.4754) -76.466  (17.3714)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 250 mg Telotristat Etiprate
Comments The primary analysis used a blocked 2-sample Wilcoxon rank sum statistic stratified by the u5-HIAA at randomization.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Wilcoxon rank sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehman estimator of difference
Estimated Value -53.955
Confidence Interval (2-Sided) 95%
-84.955 to -25.119
Estimation Comments [Not Specified]
Other Statistical Analysis Mean difference is calculated as LX1606-Placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 500 mg Telotristat Etiprate
Comments The primary analysis used a blocked 2-sample Wilcoxon rank sum statistic stratified by the u5-HIAA at randomization.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method Wilcoxon rank sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehman estimator of difference
Estimated Value -89.662
Confidence Interval (2-Sided) 95%
-113.104 to -63.863
Estimation Comments [Not Specified]
Other Statistical Analysis Mean difference is calculated as LX1606-Placebo.
3.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Open-Label Extension Period
Hide 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 First dose of study drug to within 30 days of last dose of study drug in the Open-Label Extension Period (Up to 52.6 Weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population, defined as all participants who received at least one dose of study drug, was used for analysis.
Arm/Group Title Telotristat Etiprate Open-Label Extension
Hide Arm/Group Description:
Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.
Overall Number of Participants Analyzed 67
Measure Type: Count of Participants
Unit of Measure: Participants
61
  91.0%
4.Secondary Outcome
Title Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks
Hide Description Participants recorded the number of bowel movements per day in a daily diary. The total number of BMs per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants, with data available for this endpoint were included in the analysis.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 25 25 25
Mean (Standard Deviation)
Unit of Measure: counts/day
0.050  (0.3263) -0.452  (0.6940) -0.595  (0.7240)
5.Secondary Outcome
Title Change From Baseline in Stool Form/Consistency Averaged Across All Time-Points
Hide Description Participants assessed stool form/consistency of a BM using the Bristol Stool Form Scale where: 1=hard lumps to 7=watery liquid. The daily scores were averaged over the 12-week period. A negative change indicates improvement.
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants, with data available for this endpoint were included in the analysis.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 25 25 25
Mean (Standard Deviation)
Unit of Measure: score on a scale
0.006  (0.4127) -0.196  (0.7012) -0.597  (0.8605)
6.Secondary Outcome
Title Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points
Hide Description Participants recorded the number daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants, with data available for this endpoint were included in the analysis.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 25 25 25
Mean (Standard Deviation)
Unit of Measure: counts/day
-0.333  (1.2203) -0.061  (0.9754) 0.114  (2.0992)
7.Secondary Outcome
Title Change From Baseline in Abdominal Pain Averaged Across All Time-Points
Hide Description Participants recorded abdominal pain in a daily diary. Participants evaluated the level of any abdominal pain using an 11-point numeric rating scale, where: 0=no pain to 10=worst pain ever experienced. The average daily abdominal pain was averaged over the 12-week period. A negative change from Baseline indicates improvement.
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants, with data available for this endpoint were included in the analysis.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 Week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 25 25 25
Mean (Standard Deviation)
Unit of Measure: score on a scale
-0.063  (0.7823) -0.234  (0.9697) 0.025  (0.7744)
8.Secondary Outcome
Title Change in the Frequency of Rescue Short-acting, Somatostatin Analog (SSA) Used to Treat Carcinoid Syndrome Symptoms Averaged Across All Time-Points
Hide Description The frequency (the number of times) the participant used rescue with SSA to control symptoms was recorded in a daily diary. The daily number of rescue treatments with SSA was averaged over the 12- week period. A negative change from Baseline (less use of SSA) indicates improvement.
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants, with data available for this endpoint were included in the analysis.
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 25 25 25
Mean (Standard Deviation)
Unit of Measure: counts/day
-0.013  (0.1359) -0.065  (0.3542) 0.006  (0.1030)
9.Secondary Outcome
Title Change From Baseline in the Number of Daily BMs Averaged Over the 12-Week Double-Blind Period, Among Participants Who Were Not Receiving SSA Therapy at Baseline
Hide Description Participants recorded the number of bowel movements per day in a daily diary. The total number of BMs per day were averaged over the 12-week period. A negative change from Baseline indicates improvement.
Time Frame Baseline and 12 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-treat population, all randomized participants, with data available for this endpoint were included in the analysis.The Placebo arm is not included because all participants in the Placebo arm were receiving SSA therapy at Baseline.
Arm/Group Title 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate
Hide Arm/Group Description:
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period.
Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period.
Overall Number of Participants Analyzed 3 5
Mean (Standard Deviation)
Unit of Measure: counts/day
-0.906  (0.5925) -0.98  (1.154)
Time Frame First dose of study drug to within 30 days of last dose of study drug (Up to 77.7 Weeks)
Adverse Event Reporting Description Data for the double-blind treatment period and the open-label extension period were analyzed separately. In the Non-Serious Adverse Event section, a result of "0" for a preferred term means that there are no participants in that arm above the 5% threshold.
 
Arm/Group Title Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate Telotristat Etiprate Open-Label Extension
Hide Arm/Group Description Following a 3 to 4-week run-in period, participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks, followed by a 36 week open-label extension period. Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for 12 weeks, followed by a 36 week open-label extension period. Following a 3 to 4-week run-in period, participants were randomized to receive one 250 mg telotristat etiprate tablet and one placebo-matching telotristat etiprate tablet administered three times daily for one week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the 12 week double-blind treatment period, followed by a 36 week open-label extension period. Patients previously assigned to 250 mg or 500 mg three times daily of telotristat etiprate were administered two 250 mg telotristat etiprate tablets three times daily in a 36 week open-label extension (OLE) period. Patients previously assigned to placebo were administered one 250 mg telotristat etiprate tablet plus one placebo-matching tablet three times daily for one week, followed by two 250 mg telotristat etiprate tablets three times daily for 35 weeks.
All-Cause Mortality
Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate Telotristat Etiprate Open-Label Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/26 (0.00%)   0/25 (0.00%)   0/25 (0.00%)   0/67 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate Telotristat Etiprate Open-Label Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/26 (19.23%)   1/25 (4.00%)   3/25 (12.00%)   17/67 (25.37%) 
Cardiac disorders         
Mitral valve incompetence  1  1/26 (3.85%)  0/25 (0.00%)  0/25 (0.00%)  0/67 (0.00%) 
Acute myocardial infarction  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Congenital, familial and genetic disorders         
Atrial septal defect  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Gastrointestinal disorders         
Ascites  1  0/26 (0.00%)  0/25 (0.00%)  1/25 (4.00%)  1/67 (1.49%) 
Small intestinal obstruction  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  3/67 (4.48%) 
Abdominal pain  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Hiatus hernia  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Ileus  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Lower gastrointestinal haemorrhage  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Small intestinal haemorrhage  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
General disorders         
Pyrexia  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  3/67 (4.48%) 
Infections and infestations         
Escherichia bacteraemia  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Herpes zoster ophthalmic  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Injury, poisoning and procedural complications         
Femur fracture  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Post procedural bile leak  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Wound secretion  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Investigations         
Diagnostic procedure  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Metabolism and nutrition disorders         
Dehydration  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Malignant neoplasm progression  1  1/26 (3.85%)  1/25 (4.00%)  1/25 (4.00%)  0/67 (0.00%) 
Hepatic neoplasm  1  0/26 (0.00%)  0/25 (0.00%)  1/25 (4.00%)  0/67 (0.00%) 
Neuroendocrine tumour  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Nervous system disorders         
Transient ischaemic attack  1  1/26 (3.85%)  0/25 (0.00%)  0/25 (0.00%)  0/67 (0.00%) 
Syncope  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Respiratory, thoracic and mediastinal disorders         
Bronchiectasis  1  1/26 (3.85%)  0/25 (0.00%)  0/25 (0.00%)  0/67 (0.00%) 
Sleep apnoea syndrome  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Surgical and medical procedures         
Urethral stent insertion  1  1/26 (3.85%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Hepatectomy  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  2/67 (2.99%) 
Small intestinal resection  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  2/67 (2.99%) 
Antibiotic prophylaxis  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
Therapeutic embolisation  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  1/67 (1.49%) 
1
Term from vocabulary, MedDRA (15.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 250 mg Telotristat Etiprate 500 mg Telotristat Etiprate Telotristat Etiprate Open-Label Extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/26 (80.77%)   25/25 (100.00%)   22/25 (88.00%)   61/67 (91.04%) 
Blood and lymphatic system disorders         
Anaemia  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  4/67 (5.97%) 
Gastrointestinal disorders         
Abdominal pain  1  4/26 (15.38%)  8/25 (32.00%)  1/25 (4.00%)  12/67 (17.91%) 
Diarrhoea  1  5/26 (19.23%)  4/25 (16.00%)  2/25 (8.00%)  9/67 (13.43%) 
Nausea  1  4/26 (15.38%)  3/25 (12.00%)  2/25 (8.00%)  14/67 (20.90%) 
Constipation  1  1/26 (3.85%)  4/25 (16.00%)  3/25 (12.00%)  8/67 (11.94%) 
Abdominal pain upper  1  3/26 (11.54%)  1/25 (4.00%)  2/25 (8.00%)  5/67 (7.46%) 
Abdominal distension  1  0/26 (0.00%)  3/25 (12.00%)  1/25 (4.00%)  4/67 (5.97%) 
Dyspepsia  1  2/26 (7.69%)  2/25 (8.00%)  0/25 (0.00%)  0/67 (0.00%) 
Vomiting  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  7/67 (10.45%) 
General disorders         
Fatigue  1  2/26 (7.69%)  3/25 (12.00%)  2/25 (8.00%)  7/67 (10.45%) 
Asthenia  1  2/26 (7.69%)  1/25 (4.00%)  0/25 (0.00%)  7/67 (10.45%) 
Oedema peripheral  1  0/26 (0.00%)  2/25 (8.00%)  1/25 (4.00%)  5/67 (7.46%) 
Pyrexia  1  0/26 (0.00%)  3/25 (12.00%)  0/25 (0.00%)  6/67 (8.96%) 
Infections and infestations         
Urinary tract infection  1  0/26 (0.00%)  3/25 (12.00%)  0/25 (0.00%)  0/67 (0.00%) 
Influenzae  1  0/26 (0.00%)  0/25 (0.00%)  2/25 (8.00%)  0/67 (0.00%) 
Nasopharyngitis  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  5/67 (7.46%) 
Investigations         
Gamma-glutamyltransferase increased  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  4/67 (5.97%) 
Weight decreased  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  4/67 (5.97%) 
Metabolism and nutrition disorders         
Decreased appetite  1  0/26 (0.00%)  0/25 (0.00%)  2/25 (8.00%)  6/67 (8.96%) 
Musculoskeletal and connective tissue disorders         
Myalgia  1  2/26 (7.69%)  1/25 (4.00%)  1/25 (4.00%)  0/67 (0.00%) 
Musculoskeletal pain  1  0/26 (0.00%)  0/25 (0.00%)  2/25 (8.00%)  0/67 (0.00%) 
Back pain  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  5/67 (7.46%) 
Arthralgia  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  4/67 (5.97%) 
Nervous system disorders         
Dizziness  1  3/26 (11.54%)  0/25 (0.00%)  2/25 (8.00%)  0/67 (0.00%) 
Headache  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  5/67 (7.46%) 
Presyncope  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  5/67 (7.46%) 
Psychiatric disorders         
Depressed mood  1  2/26 (7.69%)  1/25 (4.00%)  0/25 (0.00%)  0/67 (0.00%) 
Depression  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  8/67 (11.94%) 
Respiratory, thoracic and mediastinal disorders         
Oropharyngeal pain  1  0/26 (0.00%)  2/25 (8.00%)  0/25 (0.00%)  0/67 (0.00%) 
Dyspnea  1  2/26 (7.69%)  1/25 (4.00%)  0/25 (0.00%)  4/67 (5.97%) 
Cough  1  0/26 (0.00%)  0/25 (0.00%)  0/25 (0.00%)  4/67 (5.97%) 
Skin and subcutaneous tissue disorders         
Night sweats  1  0/26 (0.00%)  2/25 (8.00%)  1/25 (4.00%)  0/67 (0.00%) 
Vascular disorders         
Flushing  1  2/26 (7.69%)  3/25 (12.00%)  0/25 (0.00%)  9/67 (13.43%) 
1
Term from vocabulary, MedDRA (15.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Responsible Party: Lexicon Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02063659     History of Changes
Other Study ID Numbers: LX1606.1-303-CS
LX1606.303 ( Other Identifier: Lexicon Pharmaceuticals, Inc. )
2013-001543-31 ( EudraCT Number )
First Submitted: February 12, 2014
First Posted: February 14, 2014
Results First Submitted: April 3, 2017
Results First Posted: September 25, 2017
Last Update Posted: February 26, 2018