Trial Outcomes & Findings for TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) (NCT NCT01677910)

Last Updated: 2018-02-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

135 participants

Primary outcome timeframe

Baseline and 12 Weeks

Results posted on

2018-02-27

Participant Flow

Participants took part in the study at 48 investigative sites in Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Spain, Sweden, United Kingdom, and the United States from 08 January 2013 to 21 March 2016.

Patients with Carcinoid Syndrome not adequately controlled by somatostatin analog (SSA) therapy were assigned in a 1:1:1 ratio to receive placebo, 250 mg or 500 mg telotristat etiprate (LX1606) in the double-blind period and were eligible to receive 500 mg telotristat etiprate in the 36 week open-label extension. 136 randomized;1 patient twice.

Participant milestones

Participant milestones
Measure	Placebo Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	Telotristat Etiprate Open-Label Extension 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.
Double-Blind Treatment Period STARTED	45	45	45	0
Double-Blind Treatment Period COMPLETED	38	42	38	0
Double-Blind Treatment Period NOT COMPLETED	7	3	7	0
Open-Label Extension Period (OLE) STARTED	0	0	0	115
Open-Label Extension Period (OLE) COMPLETED	0	0	0	79
Open-Label Extension Period (OLE) NOT COMPLETED	0	0	0	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	Telotristat Etiprate Open-Label Extension 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.
Double-Blind Treatment Period Adverse Event	6	2	3	0
Double-Blind Treatment Period Physician Decision	0	0	1	0
Double-Blind Treatment Period Withdrawal of consent	1	0	3	0
Double-Blind Treatment Period Reason Not Specified	0	1	0	0
Open-Label Extension Period (OLE) Physician Decision	0	0	0	4
Open-Label Extension Period (OLE) Reason not Specified	0	0	0	2
Open-Label Extension Period (OLE) Withdrawal of Consent	0	0	0	9
Open-Label Extension Period (OLE) Lack of Efficacy	0	0	0	5
Open-Label Extension Period (OLE) Adverse Event	0	0	0	15
Open-Label Extension Period (OLE) Lost to Follow-up	0	0	0	1

Baseline Characteristics

Race information was not provided for 11 participants from France.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Baseline and 12 Weeks

Population: Participants from the Intent-to-treat population, all randomized participants, with data available were included in the analyses.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Change From Baseline in the Number of Bowel Movements (BMs) Per Day Averaged Over 12 Weeks	-0.623 counts/day Standard Deviation 0.8275	-1.433 counts/day Standard Deviation 1.3652	-1.455 counts/day Standard Deviation 1.3098

PRIMARY outcome

Timeframe: First dose of study drug to within 30 days of last dose of study drug in the Double-Blind Treatment Period (Up to 17.6 Weeks)

Population: Safety population, defined as all subjects who received at least one dose of study drug was used for analysis.

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.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in the Double-Blind Treatment Period	39 Participants	37 Participants	42 Participants

PRIMARY outcome

Timeframe: First dose of study drug to within 30 days of last dose of study drug in the Open-Label Extension Period (Up to 54.3 Weeks)

Population: Safety population, defined as all subjects who received at least one dose of study drug was used for analysis.

Outcome measures

Outcome measures
Measure	Placebo n=115 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Number of Participants With TEAEs in the Open-Label Extension Period	110 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Participants from the Intent-to-treat population, all randomized participants, with u5-HIAA data available at Baseline and Week 12 were included in the analyses.

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.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate n=32 Participants Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate n=31 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA) Levels	11.350 mg/24 hours Standard Deviation 35.0346	-40.134 mg/24 hours Standard Deviation 84.7663	-57.519 mg/24 hours Standard Deviation 82.3273

SECONDARY outcome

Timeframe: Baseline and 12 Weeks

Population: Participants from the Intent-to-treat population, all randomized participants, with data available were included in the analyses.

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.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Change From Baseline in the Number of Daily Cutaneous Flushing Episodes Averaged Across All Time-Points	-0.164 counts/day Standard Deviation 1.1572	-0.296 counts/day Standard Deviation 1.3097	-0.525 counts/day Standard Deviation 1.3413

SECONDARY outcome

Timeframe: Baseline and 12 Weeks

Population: Participants from the Intent-to-treat population, all randomized participants, with available data were included in the analyses.

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.

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.
Change From Baseline in Abdominal Pain Averaged Across All Time-Points	-0.226 units on a scale Standard Deviation 1.1601	-0.489 units on a scale Standard Deviation 1.4423	-0.333 units on a scale Standard Deviation 1.1784

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 39 other events

Deaths: 3 deaths

250 mg Telotristat Etiprate

Serious events: 7 serious events

Other events: 37 other events

Deaths: 1 deaths

500 mg Telotristat Etiprate

Serious events: 8 serious events

Other events: 42 other events

Deaths: 1 deaths

Telotristat Etiprate Open-Label Extension

Serious events: 37 serious events

Other events: 110 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Pablo Lapuerta, MD

Lexicon Pharmaceuticals, Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	250 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	500 mg Telotristat Etiprate n=45 Participants Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one telotristat etiprate 250 mg plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two telotristat etiprate (250 mg) tablets administered three times daily for 11 weeks in the double-blind treatment period, followed by a 36 week open-label extension period.	Total n=135 Participants Total of all reporting groups
Age, Continuous	63.3 years STANDARD_DEVIATION 8.67 • n=45 Participants	62.4 years STANDARD_DEVIATION 9.12 • n=45 Participants	64.9 years STANDARD_DEVIATION 9.06 • n=45 Participants	63.2 years STANDARD_DEVIATION 9.28 • n=135 Participants
Age, Customized < 65 years	25 Participants n=45 Participants	26 Participants n=45 Participants	22 Participants n=45 Participants	73 Participants n=135 Participants
Age, Customized ≥ 65 years	20 Participants n=45 Participants	19 Participants n=45 Participants	23 Participants n=45 Participants	62 Participants n=135 Participants
Sex: Female, Male Female	21 Participants n=45 Participants	24 Participants n=45 Participants	20 Participants n=45 Participants	65 Participants n=135 Participants
Sex: Female, Male Male	24 Participants n=45 Participants	21 Participants n=45 Participants	25 Participants n=45 Participants	70 Participants n=135 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=45 Participants	0 Participants n=45 Participants	1 Participants n=45 Participants	1 Participants n=135 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=45 Participants	44 Participants n=45 Participants	44 Participants n=45 Participants	133 Participants n=135 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=45 Participants	1 Participants n=45 Participants	0 Participants n=45 Participants	1 Participants n=135 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	1 Participants n=135 Participants • Race information was not provided for 11 participants from France.
Race (NIH/OMB) Asian	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=135 Participants • Race information was not provided for 11 participants from France.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=135 Participants • Race information was not provided for 11 participants from France.
Race (NIH/OMB) Black or African American	1 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	1 Participants n=135 Participants • Race information was not provided for 11 participants from France.
Race (NIH/OMB) White	40 Participants n=45 Participants • Race information was not provided for 11 participants from France.	41 Participants n=45 Participants • Race information was not provided for 11 participants from France.	40 Participants n=45 Participants • Race information was not provided for 11 participants from France.	121 Participants n=135 Participants • Race information was not provided for 11 participants from France.
Race (NIH/OMB) More than one race	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	0 Participants n=45 Participants • Race information was not provided for 11 participants from France.	1 Participants n=45 Participants • Race information was not provided for 11 participants from France.	1 Participants n=135 Participants • Race information was not provided for 11 participants from France.
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=45 Participants • Race information was not provided for 11 participants from France.	4 Participants n=45 Participants • Race information was not provided for 11 participants from France.	4 Participants n=45 Participants • Race information was not provided for 11 participants from France.	11 Participants n=135 Participants • Race information was not provided for 11 participants from France.
Region of Enrollment Canada	3 participants n=45 Participants	2 participants n=45 Participants	2 participants n=45 Participants	7 participants n=135 Participants
Region of Enrollment Sweden	3 participants n=45 Participants	3 participants n=45 Participants	3 participants n=45 Participants	9 participants n=135 Participants
Region of Enrollment Netherlands	2 participants n=45 Participants	3 participants n=45 Participants	3 participants n=45 Participants	8 participants n=135 Participants
Region of Enrollment Belgium	1 participants n=45 Participants	0 participants n=45 Participants	0 participants n=45 Participants	1 participants n=135 Participants
Region of Enrollment United States	12 participants n=45 Participants	13 participants n=45 Participants	12 participants n=45 Participants	37 participants n=135 Participants
Region of Enrollment United Kingdom	8 participants n=45 Participants	3 participants n=45 Participants	8 participants n=45 Participants	19 participants n=135 Participants
Region of Enrollment Italy	1 participants n=45 Participants	4 participants n=45 Participants	3 participants n=45 Participants	8 participants n=135 Participants
Region of Enrollment Israel	2 participants n=45 Participants	0 participants n=45 Participants	0 participants n=45 Participants	2 participants n=135 Participants
Region of Enrollment Australia	1 participants n=45 Participants	2 participants n=45 Participants	3 participants n=45 Participants	6 participants n=135 Participants
Region of Enrollment France	3 participants n=45 Participants	4 participants n=45 Participants	4 participants n=45 Participants	11 participants n=135 Participants
Region of Enrollment Germany	5 participants n=45 Participants	8 participants n=45 Participants	6 participants n=45 Participants	19 participants n=135 Participants
Region of Enrollment Spain	4 participants n=45 Participants	3 participants n=45 Participants	1 participants n=45 Participants	8 participants n=135 Participants
Somatostatin Analog (SSA) Therapy Schedule at Study Entry 3-Week	11 Participants n=45 Participants	11 Participants n=45 Participants	17 Participants n=45 Participants	39 Participants n=135 Participants
Somatostatin Analog (SSA) Therapy Schedule at Study Entry 4-Week	34 Participants n=45 Participants	34 Participants n=45 Participants	28 Participants n=45 Participants	96 Participants n=135 Participants
SSA Therapy Name at Study Entry Octreotide	30 Participants n=45 Participants	40 Participants n=45 Participants	33 Participants n=45 Participants	103 Participants n=135 Participants
SSA Therapy Name at Study Entry Lanreotide	15 Participants n=45 Participants	5 Participants n=45 Participants	12 Participants n=45 Participants	32 Participants n=135 Participants
Childbearing Potential Yes	3 Participants n=45 Participants	0 Participants n=45 Participants	0 Participants n=45 Participants	3 Participants n=135 Participants
Childbearing Potential No	18 Participants n=45 Participants	24 Participants n=45 Participants	20 Participants n=45 Participants	62 Participants n=135 Participants
Childbearing Potential Not Applicable	24 Participants n=45 Participants	21 Participants n=45 Participants	25 Participants n=45 Participants	70 Participants n=135 Participants
Urinary 5-hydroxyindoleacetic acid (u5-HIAA) at Randomization ≤ULN	12 Participants n=45 Participants	12 Participants n=45 Participants	12 Participants n=45 Participants	36 Participants n=135 Participants
Urinary 5-hydroxyindoleacetic acid (u5-HIAA) at Randomization >ULN	26 Participants n=45 Participants	26 Participants n=45 Participants	26 Participants n=45 Participants	78 Participants n=135 Participants
Urinary 5-hydroxyindoleacetic acid (u5-HIAA) at Randomization Unknown	7 Participants n=45 Participants	7 Participants n=45 Participants	7 Participants n=45 Participants	21 Participants n=135 Participants
Region North America	15 Participants n=45 Participants	15 Participants n=45 Participants	14 Participants n=45 Participants	44 Participants n=135 Participants
Region Europe	27 Participants n=45 Participants	28 Participants n=45 Participants	28 Participants n=45 Participants	83 Participants n=135 Participants
Region Rest of the World	3 Participants n=45 Participants	2 Participants n=45 Participants	3 Participants n=45 Participants	8 Participants n=135 Participants
Weight	70.87 kilogram (kg) STANDARD_DEVIATION 13.940 • n=43 Participants • Weight data was not available for all participants.	70.05 kilogram (kg) STANDARD_DEVIATION 14.832 • n=44 Participants • Weight data was not available for all participants.	73.44 kilogram (kg) STANDARD_DEVIATION 19.971 • n=44 Participants • Weight data was not available for all participants.	71.46 kilogram (kg) STANDARD_DEVIATION 16.419 • n=131 Participants • Weight data was not available for all participants.
Height	168.8 centimeter (cm) STANDARD_DEVIATION 10.707 • n=39 Participants • Height data was not available for all participants.	169.32 centimeter (cm) STANDARD_DEVIATION 9.607 • n=41 Participants • Height data was not available for all participants.	169.93 centimeter (cm) STANDARD_DEVIATION 10.436 • n=40 Participants • Height data was not available for all participants.	169.35 centimeter (cm) STANDARD_DEVIATION 10.175 • n=120 Participants • Height data was not available for all participants.
Body Mass Index (BMI)	25.13 kg/m^2 STANDARD_DEVIATION 4.790 • n=38 Participants • Not all participants had weight and height data available to calculate BMI.	24.26 kg/m^2 STANDARD_DEVIATION 4.702 • n=41 Participants • Not all participants had weight and height data available to calculate BMI.	25.24 kg/m^2 STANDARD_DEVIATION 5.352 • n=39 Participants • Not all participants had weight and height data available to calculate BMI.	24.87 kg/m^2 STANDARD_DEVIATION 4.931 • n=118 Participants • Not all participants had weight and height data available to calculate BMI.

Measure	Placebo n=45 participants at risk Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive two placebo-matching telotristat etiprate tablets administered three times daily for 12 weeks in the double-blind treatment period.	250 mg Telotristat Etiprate n=45 participants at risk Following a 3 to 4-week run-in period on stable-dose somatostatin analog (SSA) therapy (octreotide or lanreotide) participants were randomized to receive one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered three times daily for 12 Weeks in the double-blind treatment period.	500 mg Telotristat Etiprate n=45 participants at risk Following a 3 to 4-week run-in period on stable-dose SSA therapy (octreotide or lanreotide) participants were randomized to receive, one 250 mg telotristat etiprate tablet plus one placebo-matching telotristat etiprate tablet administered 3 times daily for 1 week, followed by two 250 mg telotristat etiprate tablets administered three times daily for 11 weeks in the double-blind treatment period.	Telotristat Etiprate Open-Label Extension n=115 participants at risk 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.
Gastrointestinal disorders Nausea	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	13.3% 6/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	31.1% 14/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	23.5% 27/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Abdominal pain	17.8% 8/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	22.2% 10/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	30.4% 35/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Vomiting	8.9% 4/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	13.9% 16/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.3% 13/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Abdominal distension	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.3% 13/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Diarrhoea	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	9.6% 11/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Flatulence	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	9.6% 11/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Dyspepsia	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
General disorders Fatigue	8.9% 4/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	8.9% 4/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	15.6% 7/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.3% 13/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
General disorders Asthenia	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	9.6% 11/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
General disorders Oedema peripheral	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	8.7% 10/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Infections and infestations Nasopharyngitis	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	5.2% 6/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Infections and infestations Pneumonia	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Investigations Gamma-glutamyl transferase increased	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	8.9% 4/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	8.9% 4/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.8% 9/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Investigations Alanine amino transferase increased	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Investigations Blood alkaline phosphatase increased	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Metabolism and nutrition disorders Decreased appetite	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	15.6% 7/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.3% 13/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Metabolism and nutrition disorders Hypokalaemia	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.0% 8/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Nervous system disorders Headache	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	10.4% 12/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Nervous system disorders Dizziness	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	8.9% 4/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Nervous system disorders Memory impairment	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Psychiatric disorders Depression	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	15.6% 7/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	8.7% 10/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	11.1% 5/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.1% 7/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Respiratory, thoracic and mediastinal disorders Cough	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Vascular disorders Flushing	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.1% 7/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Vascular disorders Hypertension	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	5.2% 6/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
General disorders General physical health deterioration	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.0% 8/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Psychiatric disorders Depressed mood	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.8% 9/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Psychiatric disorders Decreased interest	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.1% 7/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Psychiatric disorders Insomnia	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	5.2% 6/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Gastrointestinal disorders Constipation	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.0% 8/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.8% 9/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.0% 8/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Infections and infestations Urinary tract infection	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	8.7% 10/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
General disorders Pyrexia	4.4% 2/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	7.0% 8/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	5.2% 6/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)
Skin and subcutaneous tissue disorders Rash	6.7% 3/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	2.2% 1/45 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)	0.00% 0/115 • First dose of study drug to within 30 days of last dose of study drug (Up to 72.2 Weeks)