Trial Outcomes & Findings for Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy (NCT NCT00853047)

Last Updated: 2018-12-26

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. A TEAE was an AE reported after the first dose of randomized treatment on Day 1.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Up to 4 Weeks Core Phase

Results posted on

2018-12-26

Participant Flow

A total of 23 participants were enrolled in the Core Phase (ie, Screening and Double-blind Treatment Period) from 11 sites, including 1 satellite site, in the United States. 19 participants entered the Open-label Extension Phase.

Participant milestones

Participant milestones
Measure	Placebo Core Phase Participants received placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.	Telotristat Etiprate 150 mg Core Phase Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 250 mg Core Phase Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
Core Phase STARTED	5	3	3	3	9	0
Core Phase COMPLETED	5	3	3	2	9	0
Core Phase NOT COMPLETED	0	0	0	1	0	0
Open-Label Extension Phase STARTED	0	0	0	0	0	19
Open-Label Extension Phase Completed 8-week Extension Period	0	0	0	0	0	16
Open-Label Extension Phase COMPLETED	0	0	0	0	0	2
Open-Label Extension Phase NOT COMPLETED	0	0	0	0	0	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Telotristat Etiprate 350 mg Core Phase Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
Core Phase Participant Request	1	0
Open-Label Extension Phase Participant Request	0	7
Open-Label Extension Phase Lost to Follow-up	0	1
Open-Label Extension Phase Transfer to LX1606-302	0	2
Open-Label Extension Phase Investigator Decision	0	1
Open-Label Extension Phase Reason Not Specified	0	6

Baseline Characteristics

Study of Telotristat Etiprate (LX1606) in Participants With Symptomatic Carcinoid Syndrome Not Managed by Stable-Dose Octreotide Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Core Phase n=5 Participants Participants received placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=9 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Total n=23 Participants Total of all reporting groups
Age, Continuous	62.4 years STANDARD_DEVIATION 11.72 • n=5 Participants	51.7 years STANDARD_DEVIATION 8.08 • n=7 Participants	61.0 years STANDARD_DEVIATION 16.09 • n=5 Participants	52.7 years STANDARD_DEVIATION 9.81 • n=4 Participants	65.7 years STANDARD_DEVIATION 9.94 • n=21 Participants	60.8 years STANDARD_DEVIATION 11.39 • n=10 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants	12 Participants n=10 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants	11 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants	22 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: Up to 4 Weeks Core Phase

Population: The Safety Set Core Phase included all participants who received at least one dose of study drug in the core phase.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=9 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=5 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase Any TEAE	3 Participants	2 Participants	9 Participants	4 Participants	3 Participants
Number of Participants With Any Treatment-emergent Adverse Event (TEAE) and Any Drug-related TEAE in the Core Phase Related TEAEs	0 Participants	2 Participants	6 Participants	3 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 180 weeks in the open-label extension phase

Population: The Safety Set Extension Period included all participants who received at least one dose of study drug in the open-label extensions phase.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A TEAE was an AE reported after receiving treatment.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=19 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Number of Participants With Any TEAE in the Open-Label Extension Phase	—	—	—	18 Participants	—

SECONDARY outcome

Timeframe: Baseline to Week 4

Population: Participants from the modified Intent to Treat (mITT) Set, Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.

Participants recorded the number of BMs per day in a daily diary. The total number of BMs per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=1 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=7 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=4 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Mean Number of Bowel Movements (BMs) Per Day	-2.17 bowel movements/day Standard Deviation 2.259	-0.20 bowel movements/day Standard Deviation 0	-0.71 bowel movements/day Standard Deviation 2.048	0.82 bowel movements/day Standard Deviation 0.435	-1.37 bowel movements/day Standard Deviation 1.514

SECONDARY outcome

Timeframe: Baseline to Week 4

Population: Participants from the mITT Set Core Phase, all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug, with data available for analysis.

Participants recorded stool form in a daily diary using a 6-point scale (0-none,1-hard, 2-firm, 3-soft, 4-loose, 5-watery). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=2 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=1 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=7 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=4 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Weekly Mean Stool Form	0.00 units on a scale Standard Deviation 0.141	0.00 units on a scale Standard Deviation 0	-0.17 units on a scale Standard Deviation 0.579	-0.07 units on a scale Standard Deviation 0.222	-0.50 units on a scale Standard Deviation 0.755

SECONDARY outcome

Timeframe: Baseline to Week 4

Participants recorded the sensation of urgency to defecate (Yes or No) in a daily diary. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=1 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=7 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=4 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Percentage of Days Per Week Experiencing a Sensation of Urgency to Defecate	-32.13 percentage of days Standard Deviation 28.328	0.00 percentage of days Standard Deviation 0	-8.49 percentage of days Standard Deviation 15.742	-2.72 percentage of days Standard Deviation 5.164	-34.43 percentage of days Standard Deviation 47.261

SECONDARY outcome

Timeframe: Baseline to Week 4

Participants recorded the number of daily flushing episodes per day in a daily diary. The total number of flushing episodes per day were averaged over the 4-week period. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=1 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=7 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=4 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Number of Cutaneous Flushing Episodes	-0.30 cutaneous flushing episodes Standard Deviation 0.436	-0.10 cutaneous flushing episodes Standard Deviation 0	-0.03 cutaneous flushing episodes Standard Deviation 0.673	-0.43 cutaneous flushing episodes Standard Deviation 0.435	-0.60 cutaneous flushing episodes Standard Deviation 1.044

SECONDARY outcome

Timeframe: Baseline to Week 4

Participants recorded the severity of abdominal pain or discomfort in a daily diary assessed using a 4-point scale (0-none, 1-mild, 2-moderate, 3-severe). A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=8 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=5 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Severity of Abdominal Pain or Discomfort	-0.53 units on a scale Standard Deviation 0.808	0.03 units on a scale Standard Deviation 0.153	0.16 units on a scale Standard Deviation 0.358	0.04 units on a scale Standard Deviation 0.358	0.03 units on a scale Standard Deviation 0.586

SECONDARY outcome

Timeframe: Baseline to Week 4

Population: Participants from the Pharmacodynamic (PD) Analysis Set Core Phase, all participants who received any fraction of a dose of study drug and had a valid Baseline and at least 1 valid post-Baseline PD assessment, with data available for analysis.

u5-HIAA is a standard test used in clinical practice to assess the neuroendocrine tumor (NET) activity and is collected as a 24-hour urine specimen. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=2 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=8 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=4 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=2 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Urinary 5-hydroxyindoleacetic Acid (u5-HIAA)	-0.67 mg/24 hours Standard Deviation 0.493	13.60 mg/24 hours Standard Deviation 19.092	-35.49 mg/24 hours Standard Deviation 49.949	-20.73 mg/24 hours Standard Deviation 17.212	-27.55 mg/24 hours Standard Deviation 45.891

SECONDARY outcome

Timeframe: Baseline to Week 4

Blood samples were collected for assessment of Chromogranin A level. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=2 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=8 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=5 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=2 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Chromogranin A	-12.3 ng/mL Standard Deviation 13.05	52.5 ng/mL Standard Deviation 60.10	26011.4 ng/mL Standard Deviation 59383.95	-3251.2 ng/mL Standard Deviation 7803.84	-190.5 ng/mL Standard Deviation 225.57

SECONDARY outcome

Timeframe: Week 4

Participants were asked to answer the following question: "In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain, or discomfort?". The number of participants who answered Yes are reported.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=2 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=7 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=4 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=2 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Number of Participants Reporting Improvement in the Subjective Global Assessment of Symptoms Associated With Carcinoid Syndrome	2 Participants	1 Participants	3 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline to Week 4

Participants recorded details (location and frequency of injection) of subcutaneous injections of rescue, short-acting octreotide, if taken, in the daily diary. A negative change from Baseline indicates improvement.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=1 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=7 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=4 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Change From Baseline in Frequency of Rescue for Short-acting Octreotide Use/Day	0.03 injections per day Standard Deviation 0.058	0.00 injections per day Standard Deviation 0	-0.29 injections per day Standard Deviation 0.669	-0.38 injections per day Standard Deviation 0.695	-0.03 injections per day Standard Deviation 0.058

SECONDARY outcome

Timeframe: Baseline to Week 4

Time to the first subcutaneous injections of rescue, short-acting octreotide was determined from the participant's daily diary.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=5 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=9 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Time to First Rescue, Short-acting Octreotide	—	—	—	1.00 days Interval 1.0 to The upper limit of 95% Confidence Interval was not obtained due to the low number of participants with events.	1.00 days Interval 1.0 to The upper limit of 95% Confidence Interval was not obtained due to the low number of participants with events.

SECONDARY outcome

Timeframe: Baseline to Week 4

Population: The mITT Set Core Phase included all participants who received any fraction of a dose of study drug and had at least 1 week of data recorded in the daily diary after receiving study drug.

Complete Response to treatment was defined as one of the following: 1. Less than 4 bowel movements per day; or 2. A decrease in daily bowel movements that is ≥ 50% from baseline; or 3. A positive response to the global assessment question ("In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain or discomfort?") for each of the last 2 weeks of the Treatment Period.

Outcome measures

Outcome measures
Measure	Telotristat Etiprate 250 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=9 Participants Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=5 Participants Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).	Telotristat Etiprate 150 mg Core Phase n=3 Participants Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.
Number of Participants Experiencing Complete Response at Week 4	2 Participants	1 Participants	2 Participants	0 Participants	1 Participants

Adverse Events

Placebo Core Phase

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Telotristat Etiprate 150 mg Core Phase

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Telotristat Etiprate 250 mg Core Phase

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Telotristat Etiprate 350 mg Core Phase

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Telotristat Etiprate 500 mg Core Phase

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Telotristat Etiprate Open-Label Extension Phase

Serious events: 8 serious events

Other events: 18 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Core Phase n=5 participants at risk Participants received placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.	Telotristat Etiprate 150 mg Core Phase n=3 participants at risk Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 250 mg Core Phase n=3 participants at risk Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=3 participants at risk Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=9 participants at risk Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=19 participants at risk Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
Gastrointestinal disorders Nausea	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Surgical and medical procedures Mass excision	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Surgical and medical procedures Small intestinal resection	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Vascular disorders Hypertensive crisis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Intestinal perforation	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Surgical and medical procedures Cholecystectomy	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Disease progression	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure chronic	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Pulmonary valve stenosis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Tricuspid valve incompetence	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure acute	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Placebo Core Phase n=5 participants at risk Participants received placebo-matching telotristat etiprate capsules, orally 3 times daily for 28 days in the double-blind treatment period (core phase) in combination with stable-dose octreotide long-acting release (LAR) depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to receive telotristat etiprate in the optional open-label extension period.	Telotristat Etiprate 150 mg Core Phase n=3 participants at risk Participants received telotristat etiprate capsules,150 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 250 mg Core Phase n=3 participants at risk Participants received telotristat etiprate capsules, 250 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 350 mg Core Phase n=3 participants at risk Participants received telotristat etiprate capsules, 350 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate 500 mg Core Phase n=9 participants at risk Participants received telotristat etiprate capsules, 500 mg orally 3 times daily for 28 days in the double-blind treatment period in combination with a stable-dose octreotide LAR depot therapy given once per month. Upon completion of 28-days of treatment, participants were eligible to enter the optional open-label extension period.	Telotristat Etiprate Open-Label Extension Phase n=19 participants at risk Participants received telotristat etiprate at assigned dose level for 8 weeks in combination with stable-dose octreotide LAR depot therapy given once per month in the open-label extension period. Upon completion of the 8-week period, participants could enter an additional extension period of 172 weeks, receiving telotristat etiprate at the assigned dose or maximum tolerated dose (500 mg 3 times daily).
Gastrointestinal disorders Diarrhoea	40.0% 2/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	66.7% 2/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	44.4% 4/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	52.6% 10/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	44.4% 4/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	47.4% 9/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	15.8% 3/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal Pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	31.6% 6/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Fatigue	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	22.2% 2/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	36.8% 7/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Early satiety	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	22.2% 2/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	26.3% 5/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	22.2% 2/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	21.1% 4/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	22.2% 2/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Vascular disorders Flushing	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	22.2% 2/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	36.8% 7/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	21.1% 4/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	15.8% 3/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	31.6% 6/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	21.1% 4/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Oedema peripheral	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Pyrexia	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Infections and infestations Bronchitis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	15.8% 3/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Weight decreased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	21.1% 4/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	15.8% 3/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	15.8% 3/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	15.8% 3/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Headache	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	15.8% 3/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Sinus headache	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Vascular disorders Hypertension	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	10.5% 2/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Palpitations	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Cardiac disorders Pulmonary valve incompetence	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Eye disorders Blepharitis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Eye disorders Keratoconjunctivitis sicca	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Eye disorders Photophobia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Eye disorders Vision blurred	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Eye disorders Visual impairment	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Diverticulum intestinal	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Haematochezia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Malabsorption	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Melaena	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Proctalgia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Retching	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Steatorrhoea	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Chest discomfort	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Chills	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Feeling cold	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Infusion site swelling	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Injection site haematoma	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Local swelling	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Nodule	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Hepatobiliary disorders Hepatic pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection bacterial	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Joint sprain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Activated partial thromboplastin time prolonged	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Alanine aminotransferase increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Blood bilirubin increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Blood cholesterol increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Cardiac murmur	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Haemoglobin decreased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Weight increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Fluid overload	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Folate deficiency	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Malnutrition	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Vitamin A deficiency	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Vitamin B12 deficiency	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Vitamin E deficiency	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Vitamin K deficiency	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Memory impairment	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Psychiatric disorders Depression	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Psychiatric disorders Mood altered	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Dysuria	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Haematuria	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Hydronephrosis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Reproductive system and breast disorders Prostatomegaly	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Reproductive system and breast disorders Scrotal pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Apnoea	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory tract congestion	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract congestion	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis acneiform	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Skin discolouration	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Vascular disorders Hot flush	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Epigastric discomfort	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal hypermotility	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Haemorrhoids	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Toothache	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Feeling abnormal	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Blood alkaline phophatase increased	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Blood glucose decreased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Blood triglycerides increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Low density lipoprotein increased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Neutrophil count increased	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Protein total decreased	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations Urine colour abnormal	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Investigations White blood cell count increased	20.0% 1/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Urine abnormality	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Psychiatric disorders Sleep disorder	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Reproductive system and breast disorders Scrotal oedema	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Acne	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dry Skin	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Vascular disorders Peripheral coldness	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Infections and infestations Herpes zoster	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Bilirubinuria	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Oliguria	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Proteinuria	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	11.1% 1/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Renal and urinary disorders Urinary hesitation	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	33.3% 1/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Faecal incontinence	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.
Nervous system disorders Lethargy	0.00% 0/5 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/3 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	0.00% 0/9 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.	5.3% 1/19 • Adverse event data was collected during the core phase over 4 weeks and up to 180 weeks in the extension phase Safety Set included all participants who received at least one dose of study drug.

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