Trial Outcomes & Findings for Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome (NCT NCT01104415)

Last Updated: 2019-03-15

Results Overview

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. Treatment-emergent AEs were defined as any AEs reported after the first dose of treatment on Day 1.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Baseline up to Week 12 in the Core Phase

Results posted on

2019-03-15

Participant Flow

A total of 15 participants were enrolled in the Core Phase (8-week Dose-escalation Period and the 4-week Stable-dose Period) from 11 sites in the United Kingdom and Germany, and 11 participants entered the Open-label Extension Period.

Participant milestones

Participant milestones
Measure	Telotristat Etiprate- Core Phase Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate -Extension Period Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Core Phase STARTED	15	0
Core Phase COMPLETED	14	0
Core Phase NOT COMPLETED	1	0
Extension Period STARTED	0	11
Extension Period COMPLETED	0	0
Extension Period NOT COMPLETED	0	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Telotristat Etiprate- Core Phase Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate -Extension Period Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Core Phase Consent withdrawn by subjects	1	0
Extension Period Progressive disease	0	4
Extension Period Death	0	1
Extension Period Physician Decision	0	1
Extension Period Transition to Study LX1606.302	0	4
Extension Period Heart surgery/feeling miserable	0	1

Baseline Characteristics

Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Telotristat Etiprate- Core Phase n=15 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.
Age, Continuous	61.1 years STANDARD_DEVIATION 9.35 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race/Ethnicity, Customized White	15 Participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants
Region of Enrollment Germany	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 12 in the Core Phase

Population: The safety set (SS) included all the enrolled participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=15 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase Any TEAE	15 Participants	—
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Core Phase Drug-Related TEAE	5 Participants	—

PRIMARY outcome

Timeframe: Up to 124 Weeks in the Extension Period

Population: SS included all enrolled participants who had received at least 1 dose of study drug in the 124-week Extension Period.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=11 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period Any TEAE	11 Participants	—
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs) and Drug-Related TEAEs in the Extension Period Drug-Related TEAE	4 Participants	—

SECONDARY outcome

Timeframe: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24

Population: Efficacy full analysis set (EFAS) in Core Phase included all participants with at least 1 post-Baseline efficacy assessment and full analysis set (FAS) in Extension Period(EP) included all participants in SS with at least 1 post-Baseline efficacy assessment in 124-week EP. Number analyzed is the participants with evaluable data at given time point.

Participants recorded the number of bowel movements in a daily diary. The change from baseline value was calculated as the difference between mean numbers of BMs of the post-baseline interval (Weeks 9 to 12) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=14 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=8 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Change From Baseline in Number of Bowel Movements (BMs)	-2.60 number of bowel movements/day Standard Deviation 1.381	-2.85 number of bowel movements/day Standard Deviation 1.64

SECONDARY outcome

Timeframe: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24

Population: EFAS in the Core Phase included all participants who had at least 1 post-Baseline efficacy assessment and FAS in the Extension period included all participants in the safety set who had at least 1 post-Baseline efficacy assessment in 124-week Extension Period. Number analyzed is the number of participants with evaluable data at given time-point.

Participants assessed stool form/consistency in a daily diary using a 6-point scale (0-none, 1-hard, 2-firm, 3-soft, 4-loose, 5-watery). The change from the baseline value was calculated as the difference between a mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score and 5 indicates the worst score. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=14 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=8 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Change From Baseline in Stool Form/Consistency	-0.79 score on a scale Standard Deviation 0.707	-1.31 score on a scale Standard Deviation 0.666

SECONDARY outcome

Timeframe: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24

Population: EFAS in Core Phase included all participants who had at least 1 post-Baseline efficacy assessment and FAS in Extension Period included all participants in the safety set who had at least 1 post-Baseline efficacy assessment in the 124-week Extension Period. Number analyzed is the number of participants with evaluable data at the given time-point.

Participants assessed the urgency to defecate using a daily diary response to the following question, "Have you felt or experienced a sense of urgency to pass stool today?". The change from the baseline value was calculated as the difference between the mean score (percentage of days) of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=14 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=8 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Change From Baseline in Percentage of Days With Sensation of Urgency to Defecate	-11.32 percentage of days Standard Deviation 36.660	-22.79 percentage of days Standard Deviation 49.546

SECONDARY outcome

Timeframe: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24

Sensation/severity of nausea was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of nausea experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicates the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=13 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=7 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Change From Baseline in Sensation/Severity of Nausea Using 100 mm Visual Analog Scale (VAS)	-2.43 score on a scale Standard Deviation 5.208	-5.71 score on a scale Standard Deviation 8.797

SECONDARY outcome

Timeframe: Core Phase: Weeks 9-12; Extension Period: Week 24

Participants assessed their symptoms using a weekly subjective response to the following question, "In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain, or discomfort?". The values for improvement in global assessment of symptoms associated with carcinoid syndrome in the Core Phase were averaged from Weeks 9 to 12.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=13 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=7 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Number of Participants With an Improvement in Global Assessment of Symptoms Associated With Carcinoid Syndrome	10 Participants	4 Participants

SECONDARY outcome

Timeframe: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24

The severity of abdominal pain was measured using a 100 mm VAS. Participants rated their perception of the sensation/severity of abdominal pain or experienced by marking a single vertical line on a VAS scale from 0 to 100 mm, where 0 = No vomiting and 100 = vomiting. The change from the baseline value was calculated as the difference between the mean score of the post-baseline interval (Weeks 9 to 12) and baseline. 0 indicate the best score, 100 indicates the worst score. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=14 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=7 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Change From Baseline in Daily Severity of Abdominal Pain or Discomfort Using 100 mm Visual Analog Scale (VAS)	-8.66 score on a scale Standard Deviation 18.724	-24.11 score on a scale Standard Deviation 19.643

SECONDARY outcome

Timeframe: Core Phase: Baseline to Weeks 9-12; Extension Period: Baseline to Week 24

Participants recorded the number of daily cutaneous flushing episodes experienced in the daily diary. The change from baseline value was calculated as the difference between the mean numbers of cutaneous flushing episodes of the post-baseline interval (Weeks 9 to 12) and baseline. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=14 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=8 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Change From Baseline in Daily Number of Cutaneous Flushing Episodes	-0.88 Daily number of flushing episodes Standard Deviation 1.205	-1.55 Daily number of flushing episodes Standard Deviation 1.784

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: EFAS included all participants who had at least 1 post-baseline efficacy assessment.

Clinically meaningful symptom reduction was defined as either: a) an average of \< 4 bowel movements per day over 15 consecutive days, b) a 50% reduction from baseline in the number of bowel movements, c) a positive response to the question regarding adequate relief, or d) a 50% reduction from baseline in the number of daily flushing episodes.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=15 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Number of Participants Achieving Clinically Meaningful Symptom Reduction in the Core Phase	14 Participants	—

SECONDARY outcome

Timeframe: Core Phase: Baseline to Week 12; Extension Period: Baseline to Weeks 20-21

Population: Pharmacodynamic (PD) analysis set included all participants who had received at least 1 dose of study drug, had a valid baseline PD assessment, and at least 1 valid post-baseline PD assessment (whole blood 5-HT or u5-HIAA) in Core Phase and Extension Period.

Urinary 5-HIAA (u5-HIAA) is a standard test used in clinical practice to assess the neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. The change from baseline value for the Extension Period was calculated as the difference between mean change in 5-HIAA of the post-baseline interval (Weeks 20 to 21) and baseline. A negative change from baseline indicates improvement. Baseline for the Extension Period was defined as non-missing assessment in Run-in period prior to the first dose of study drug.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate- Core Phase n=8 Participants Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=6 Participants Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Change From Baseline in Urinary 5-Hydroxyindoleacetic Acid (HIAA) Levels	-97.26 mg/24 hours Standard Deviation 164.995	-65.02 mg/24 hours Standard Deviation 119.350

Adverse Events

Telotristat Etiprate- Core Phase

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Telotristat Etiprate- Extension Period

Serious events: 7 serious events

Other events: 11 other events

Deaths: 1 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	Telotristat Etiprate- Core Phase n=15 participants at risk Following a 2-week Run-In Period, participants received telotristat etiprate capsules at a starting dose of 150 mg, orally three times daily (TID) for 14 days in the Core Phase. Dose escalations (250 mg, 350 mg, 500 mg) occurred serially every 14 days, up to a maximum dosage of telotristat etiprate 500 mg TID, as guided by specific clinical criteria for dose escalation. Upon completion of 12 weeks of treatment, participants were eligible to receive telotristat etiprate in the optional Open-label Extension Period.	Telotristat Etiprate- Extension Period n=11 participants at risk Participants received telotristat etiprate at their highest tolerated dose (250 mg or 500 mg), orally, TID for 124 weeks in the Open-label Extension Period. If neither dose was tolerated participants were discontinued from the study and completed the 2-week Follow-up Visit.
Gastrointestinal disorders Abdominal Pain	6.7% 1/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	0.00% 0/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Vascular disorders Hypertension	6.7% 1/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	0.00% 0/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Infections and infestations Rhinitis	6.7% 1/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	0.00% 0/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Gastrointestinal disorders Diarrhoea	6.7% 1/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	0.00% 0/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Infections and infestations Gastroenteritis	6.7% 1/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	0.00% 0/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Nervous system disorders Epilepsy	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Surgical and medical procedures Cardiac operation	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Surgical and medical procedures Inguinal hernia repair	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Surgical and medical procedures Therapeutic embolisation	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	18.2% 2/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Endocrine disorders Carcinoid syndrome	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Infections and infestations Bronchitis	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Cardiac disorders Carcinoid heart disease	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Gastrointestinal disorders Intestinal obstruction	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/15 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period	9.1% 1/11 • Adverse event data was collected for up to 12 weeks in the Core Phase, up to 124 weeks in the Extension Period and up to 2 weeks in the Follow-up Period