Trial Outcomes & Findings for Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib (NCT NCT00756509)

NCT ID: NCT00756509

Last Updated: 2026-01-20

Results Overview

The primary efficacy measure is the proportion of patients reaching Complete Response (CR), Partial Response (PR), or Stable Disease (SD) by Month 6, as per RECIST v1.0. Definitions are as follows: CR requires at least two CRs at least four weeks apart before any progression; PR requires two or more PRs at least four weeks apart, without qualifying for CR; SD is at least one SD more than six weeks after treatment start, not qualifying for CR or PR. Progressive Disease (PD) is defined as progression or cancer-related death within 12 weeks of starting treatment, not qualifying for CR, PR, or SD. UNK refers to cases not meeting these criteria, such as absence of confirmed CR/PR, no SD after six weeks, or early progression. The percentage of patients with CR, PR, or SD will be presented with a one-sided exact 90% (or 80% two-sided) confidence interval for the ITT\_F group.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 34 participants
• Primary outcome timeframe: from baseline to month 6, core phase
• Results posted on: 2026-01-20

Participant Flow

Study consists of participants with unresectable or metastatic gastrointestinal stromal tumors (GIST) showing progression of disease from 5 countries: Germany, Spain, Finland, France, Italy

All enrolled participants received 400 mg bid dose of nilotinib.

Participant milestones

Measure	Nilotinib Participants who received 400 mg bid of nilotinib
Core Phase STARTED	41
Core Phase COMPLETED	31
Core Phase NOT COMPLETED	10
Follow-Up Phase STARTED	31
Follow-Up Phase COMPLETED	7
Follow-Up Phase NOT COMPLETED	24

Reasons for withdrawal

Measure	Nilotinib Participants who received 400 mg bid of nilotinib
Core Phase Adverse Event	2
Core Phase Lack of Efficacy	2
Core Phase Disease progression	6
Follow-Up Phase Missing values	2
Follow-Up Phase Disease progression	9
Follow-Up Phase Administrative problems	3
Follow-Up Phase Lost to Follow-up	1
Follow-Up Phase Withdrawal by Subject	1
Follow-Up Phase Subject's condition no longer requires study drug	1
Follow-Up Phase Adverse Event	7

Baseline Characteristics

Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib

Baseline characteristics by cohort

Measure	Nilotinib n=41 Participants Participants who received 400 mg bid of nilotinib
Age, Continuous	58 Years STANDARD_DEVIATION 10.4 • n=37 Participants
Sex: Female, Male Female	19 Participants n=37 Participants
Sex: Female, Male Male	22 Participants n=37 Participants
Race/Ethnicity, Customized Caucasian	40 Participants n=37 Participants
Race/Ethnicity, Customized Black	1 Participants n=37 Participants

PRIMARY outcome

Timeframe: from baseline to month 6, core phase

Population: The intent-to-treat (ITT) population consisted of all participants who received at least one dose of the study drug and had at least one post-baseline assessment of the primary efficacy variable (assessment according to RECIST). Participants without any post-baseline assessment of tumour were included if they were defined as progressive disease based on clinical evaluation.

The primary efficacy measure is the proportion of patients reaching Complete Response (CR), Partial Response (PR), or Stable Disease (SD) by Month 6, as per RECIST v1.0. Definitions are as follows: CR requires at least two CRs at least four weeks apart before any progression; PR requires two or more PRs at least four weeks apart, without qualifying for CR; SD is at least one SD more than six weeks after treatment start, not qualifying for CR or PR. Progressive Disease (PD) is defined as progression or cancer-related death within 12 weeks of starting treatment, not qualifying for CR, PR, or SD. UNK refers to cases not meeting these criteria, such as absence of confirmed CR/PR, no SD after six weeks, or early progression. The percentage of patients with CR, PR, or SD will be presented with a one-sided exact 90% (or 80% two-sided) confidence interval for the ITT_F group.

Outcome measures

Measure	Nilotinib n=41 Participants Participants who received 400 mg bid of nilotinib
Proportion of Participants With Best Overall Response at Month 6 (Core Phase) Determined According to the RECIST v1.0. Complete Response (CR)	0 Participants
Proportion of Participants With Best Overall Response at Month 6 (Core Phase) Determined According to the RECIST v1.0. Partial Response (PR)	14 Participants
Proportion of Participants With Best Overall Response at Month 6 (Core Phase) Determined According to the RECIST v1.0. Stable Disease (SD)	21 Participants
Proportion of Participants With Best Overall Response at Month 6 (Core Phase) Determined According to the RECIST v1.0. Progressive Disease (PD)	6 Participants
Proportion of Participants With Best Overall Response at Month 6 (Core Phase) Determined According to the RECIST v1.0. Unknown (UNK)	0 Participants

SECONDARY outcome

Timeframe: from baseline to month 6, core phase

Population: The intent-to-treat (ITT) population consisted of all participants who received at least one dose of the study drug and had at least one post-baseline assessment of the primary efficacy variable (assessment according to RECIST). Participants without any post-baseline assessment of tumour were included if they were defined as progressive disease based on clinical evaluation.

Objective Response Rate (ORR) is defined as the proportion of patients in whom a complete (CR) or partial (PR) response was observed according to RECIST at month 6.

Outcome measures

Measure	Nilotinib n=41 Participants Participants who received 400 mg bid of nilotinib
Proportion of Participants With Objective Response Rate (ORR) at Month 6 (Core Phase) Observed According to RECIST	34.1 Percentage of responder Interval 24.2 to 45.3

SECONDARY outcome

Timeframe: from baseline to month 6, core phase

Population: The intent-to-treat (ITT) population consisted of all participants who received at least one dose of the study drug and had at least one post-baseline assessment of the primary efficacy variable (assessment according to RECIST). Participants without any post-baseline assessment of tumour were included if they were defined as progressive disease based on clinical evaluation.

Time to response is defined as the time from start of treatment to the first objective tumor response (PR or CR) observed. Patients who did not achieve a confirmed PR or CR will be censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease).

Outcome measures

Measure	Nilotinib n=41 Participants Participants who received 400 mg bid of nilotinib
Time to Response (TTR) at Month 6 (Core Phase)	62 Days Interval 57.0 to The upper bound of the confidence interval was not estimable due to insufficient events.

SECONDARY outcome

Timeframe: from date of first response (CR or PR) until progression or death, up to data cut off (up to approximately 16 years)

Population: The intent-to-treat (ITT) population consisted of all participants who received at least one dose of the study drug and had at least one post-baseline assessment of the primary efficacy variable (assessment according to RECIST). Participants without any post-baseline assessment of tumour were included if they were defined as progressive disease based on clinical evaluation.

Duration of response is defined as the time from onset of response (CR/PR) to objective tumor progression or death from any cause. Patients not experiencing progression or death will be censored with the date of their last adequate tumor assessment.

Outcome measures

Measure	Nilotinib n=21 Participants Participants who received 400 mg bid of nilotinib
Duration of Response (CR or PR) for Complete Study (Core and Follow-up Phases)	2722 Days Interval 588.0 to The upper bound of the confidence interval was not estimable due to insufficient events.

SECONDARY outcome

Timeframe: from date of first response (CR or PR) until progression or death, up to data cut off (up to approximately 16 years)

Population: The intent-to-treat (ITT) population consisted of all participants who received at least one dose of the study drug and had at least one post-baseline assessment of the primary efficacy variable (assessment according to RECIST). Participants without any post-baseline assessment of tumour were included if they were defined as progressive disease based on clinical evaluation.

Progression-free survival (PFS) is defined as the time from first study drug administration to objective tumor progression or death from any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS will be explored graphically by presenting the Kaplan-Meier curve.

Outcome measures

Measure	Nilotinib n=31 Participants Participants who received 400 mg bid of nilotinib
Progression-free Survival (PFS) for Complete Study (Core and Follow-up Phases)	2833 Days Interval 791.0 to The upper bound of the confidence interval was not estimable due to insufficient events.

SECONDARY outcome

Timeframe: from date of first response (CR or PR) until progression or death, up to data cut off (up to approximately 16 years)

Population: The intent-to-treat (ITT) population consisted of all participants who received at least one dose of the study drug.

Overall Survival (OS) is defined as the time from first study drug administration to death from any cause. Participants alive at their last known follow-up were censored. No deaths occurred during the study.

Outcome measures

Measure	Nilotinib n=41 Participants Participants who received 400 mg bid of nilotinib
Overall Survival for Complete Study (Core and Follow-up Phases)	NA years Standard Deviation NA Overall survival could not be calculated due to an insufficient number of events

SECONDARY outcome

Timeframe: from the first dose through the end of the study (core and follow-up phases): including all visits up to the follow-up database lock (approximately 16 years)

Population: The intent-to-treat (ITT) population consisted of all participants who received at least one dose of the study drug and had at least one post-baseline assessment of the primary efficacy variable (assessment according to RECIST). Participants without any post-baseline assessment of tumour were included if they were defined as progressive disease based on clinical evaluation.

This measure summarizes the proportion of participants who experienced at least one treatment-emergent adverse event (TEAE) during the entire study period, including both core and follow-up phases. A TEAE was defined as an adverse event that began or worsened after the first dose of study treatment.

Outcome measures

Measure	Nilotinib n=41 Participants Participants who received 400 mg bid of nilotinib
Proportion of Participants With Treatment-emergent Adverse Events During the Entire Study (Core and Follow-up Phases)	39 Participants

Adverse Events

Total Core

Serious events: 10 serious events

Other events: 39 other events

Deaths: 0 deaths

Total Follow up

Serious events: 14 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Total Core n=41 participants at risk Total Core phase	Total Follow up n=31 participants at risk Total Follow up phase
Cardiac disorders MYOCARDIAL INFARCTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders ABDOMINAL PAIN	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders DIARRHOEA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders SUBILEUS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders CHEST PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders PYREXIA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations HAEMOGLOBIN DECREASED	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERCALCAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) TUMOUR RUPTURE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders ARTERIAL THROMBOSIS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders CARDIAC FAILURE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders CARDIAC FAILURE CHRONIC	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders CARDIAC FAILURE CONGESTIVE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders CARDIO-RESPIRATORY ARREST	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders CORONARY ARTERY DISEASE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders PERICARDIAL EFFUSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders SUPRAVENTRICULAR TACHYCARDIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Ear and labyrinth disorders VERTIGO	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Ear and labyrinth disorders VESTIBULAR DISORDER	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Endocrine disorders TOXIC NODULAR GOITRE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders GLAUCOMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders OCULAR HYPERTENSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders GENERAL PHYSICAL HEALTH DETERIORATION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders HYPERPLASIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders VASCULAR STENT STENOSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Immune system disorders MULTIPLE SCLEROSIS RELAPSE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations SEPSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations STREPTOCOCCAL SEPSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications ARTERIAL RESTENOSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) KERATOACANTHOMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PLASMA CELL MYELOMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders CAROTID ARTERY STENOSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders HEADACHE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders NEURITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders DEPRESSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders ACUTE KIDNEY INJURY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders PULMONARY HYPERTENSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders CIRCULATORY COLLAPSE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).

Other adverse events

Measure	Total Core n=41 participants at risk Total Core phase	Total Follow up n=31 participants at risk Total Follow up phase
Blood and lymphatic system disorders ANAEMIA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	12.9% 4/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Blood and lymphatic system disorders NEUTROPENIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders PALPITATIONS	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Ear and labyrinth disorders HYPOACUSIS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Endocrine disorders GOITRE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders ABNORMAL SENSATION IN EYE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders DRY EYE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders EYELID PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders OCULAR HYPERAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders ABDOMINAL PAIN	26.8% 11/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	25.8% 8/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders ABDOMINAL PAIN LOWER	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders ABDOMINAL PAIN UPPER	9.8% 4/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders CONSTIPATION	17.1% 7/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	29.0% 9/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders DIARRHOEA	19.5% 8/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders DYSPEPSIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders DYSPHAGIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders FLATULENCE	9.8% 4/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders GASTRIC POLYPS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders GASTRITIS EROSIVE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders HAEMORRHOIDS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders HIATUS HERNIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders NAUSEA	19.5% 8/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders TOOTHACHE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders VOMITING	9.8% 4/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	12.9% 4/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders ASTHENIA	26.8% 11/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders CHEST DISCOMFORT	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders CHEST PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders FACE OEDEMA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders FATIGUE	24.4% 10/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders FEELING COLD	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders LOCAL SWELLING	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders MUCOSAL INFLAMMATION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders OEDEMA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders OEDEMA PERIPHERAL	19.5% 8/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	22.6% 7/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders PYREXIA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders THIRST	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Hepatobiliary disorders HEPATITIS TOXIC	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Hepatobiliary disorders HEPATOTOXICITY	7.3% 3/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Hepatobiliary disorders HYPERBILIRUBINAEMIA	14.6% 6/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	12.9% 4/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Hepatobiliary disorders HYPERTRANSAMINASAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations CYSTITIS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations EAR INFECTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations FEBRILE INFECTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations GASTROENTERITIS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations HERPES ZOSTER	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations NASOPHARYNGITIS	19.5% 8/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	19.4% 6/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations ORAL HERPES	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations RESPIRATORY TRACT INFECTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations TOOTH ABSCESS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations TOOTH INFECTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations VIRAL INFECTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations ALANINE AMINOTRANSFERASE INCREASED	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations BLOOD AMYLASE INCREASED	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations BLOOD BILIRUBIN INCREASED	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations BLOOD CREATININE INCREASED	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations BLOOD GLUCOSE INCREASED	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations GAMMA-GLUTAMYLTRANSFERASE INCREASED	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations LIPASE INCREASED	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations TRANSAMINASES INCREASED	12.2% 5/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders DECREASED APPETITE	12.2% 5/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERCALCAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERCHOLESTEROLAEMIA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERKALAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERLIPASAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERURICAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPOPHOSPHATAEMIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders ARTHRALGIA	19.5% 8/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	12.9% 4/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders BACK PAIN	12.2% 5/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders BONE PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders FLANK PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders GROIN PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders JOINT SWELLING	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	12.2% 5/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders MUSCLE TIGHTNESS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders MYALGIA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders NECK PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	12.2% 5/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	12.9% 4/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SKIN PAPILLOMA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SPINAL HAEMANGIOMA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders DIZZINESS	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders DYSGEUSIA	9.8% 4/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders HEADACHE	26.8% 11/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders MEMORY IMPAIRMENT	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders PARAESTHESIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders PERIPHERAL SENSORY NEUROPATHY	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders ANXIETY	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders ILLUSION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders INSOMNIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders NERVOUSNESS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders RESTLESSNESS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders SLEEP DISORDER	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders HAEMATURIA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders NOCTURIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders POLLAKIURIA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders RENAL FAILURE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Reproductive system and breast disorders ERECTILE DYSFUNCTION	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Reproductive system and breast disorders NIPPLE OEDEMA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Reproductive system and breast disorders NIPPLE PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Reproductive system and breast disorders PELVIC PAIN	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Reproductive system and breast disorders TESTIS DISCOMFORT	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders COUGH	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders DYSPHONIA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders DYSPNOEA	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders PLEURAL EFFUSION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders THROAT IRRITATION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders ALOPECIA	19.5% 8/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	29.0% 9/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders DRY SKIN	19.5% 8/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	25.8% 8/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders ECZEMA	7.3% 3/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders ERYTHEMA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders HYPERHIDROSIS	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders NIGHT SWEATS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders PALMAR-PLANTAR ERYTHRODYSAESTHESIA SYNDROME	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders PETECHIAE	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders PHOTOSENSITIVITY REACTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders PILOERECTION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	0.00% 0/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders PRURITUS	26.8% 11/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders RASH	24.4% 10/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	19.4% 6/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders XANTHELASMA	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders ARTERIOSCLEROSIS	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders HOT FLUSH	4.9% 2/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders HYPERTENSION	2.4% 1/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Blood and lymphatic system disorders AGRANULOCYTOSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Blood and lymphatic system disorders SPLENIC INFARCTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders ANGINA PECTORIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders CARDIAC FAILURE CONGESTIVE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders CORONARY ARTERY DISEASE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders MITRAL VALVE INCOMPETENCE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Cardiac disorders PERICARDIAL EFFUSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Ear and labyrinth disorders EAR SWELLING	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Ear and labyrinth disorders EXTERNAL EAR INFLAMMATION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Ear and labyrinth disorders TINNITUS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Ear and labyrinth disorders VERTIGO	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	16.1% 5/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Endocrine disorders HYPERTHYROIDISM	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders CONJUNCTIVAL HAEMORRHAGE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders EYE PAIN	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders GLAUCOMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders OCULAR HYPERTENSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Eye disorders PERIORBITAL OEDEMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders ABDOMINAL DISCOMFORT	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders AEROPHAGIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders ASCITES	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders DIVERTICULUM INTESTINAL	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders DRY MOUTH	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders EPIGASTRIC DISCOMFORT	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders GASTRITIS HAEMORRHAGIC	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders GINGIVAL RECESSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders HAEMATOCHEZIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders LIP ULCERATION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Gastrointestinal disorders REFLUX GASTRITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders INFLAMMATION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders INFUSION SITE EXTRAVASATION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders MALAISE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
General disorders PSEUDOCYST	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Hepatobiliary disorders CHOLELITHIASIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Hepatobiliary disorders HEPATIC PAIN	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Immune system disorders MULTIPLE SCLEROSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Immune system disorders MULTIPLE SCLEROSIS RELAPSE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations BRONCHITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations CONJUNCTIVITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations CORONAVIRUS INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations EYE INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations FOLLICULITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations GANGRENE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations GASTROINTESTINAL INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations HERPES SIMPLEX	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations LOCALISED INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations ONYCHOMYCOSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations PERIODONTITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations PNEUMONIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations RESPIRATORY TRACT INFECTION VIRAL	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations SINUSITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations SKIN INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations URINARY TRACT INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Infections and infestations WOUND INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications ARTHROPOD BITE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications CONTUSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications FRACTURE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications JOINT DISLOCATION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications RIB FRACTURE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications SKIN ABRASION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications SPLINTER	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications THORACIC VERTEBRAL FRACTURE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Injury, poisoning and procedural complications WOUND	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations AMYLASE INCREASED	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	9.7% 3/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations ASPARTATE AMINOTRANSFERASE INCREASED	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations C-REACTIVE PROTEIN INCREASED	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations CARDIAC MURMUR	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations COLONOSCOPY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations ELECTROCARDIOGRAM QT PROLONGED	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Investigations INTRAOCULAR PRESSURE INCREASED	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders DIABETES MELLITUS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders FOLATE DEFICIENCY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders GOUT	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERAMYLASAEMIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERGLYCAEMIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERNATRAEMIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPERPROTEINAEMIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPOALBUMINAEMIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders HYPONATRAEMIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders IRON DEFICIENCY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders TYPE 2 DIABETES MELLITUS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Metabolism and nutrition disorders VITAMIN D DEFICIENCY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL CHEST PAIN	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders OSTEOARTHRITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders OSTEOCHONDROSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Musculoskeletal and connective tissue disorders OSTEOLYSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) BASAL CELL CARCINOMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) HAEMANGIOMA OF BONE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PAPILLOMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders CAROTID ARTERY STENOSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders CEREBROVASCULAR DISORDER	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders DECREASED VIBRATORY SENSE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders DISTURBANCE IN ATTENTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders HYPOAESTHESIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders NYSTAGMUS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders PARESIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders PARTIAL SEIZURES	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders POLYNEUROPATHY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Nervous system disorders VASCULAR DEMENTIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders ANXIETY DISORDER	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders CONFUSIONAL STATE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders MOOD SWINGS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Psychiatric disorders PANIC ATTACK	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders BLADDER DISCOMFORT	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders CALCULUS URINARY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders CHRONIC KIDNEY DISEASE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	6.5% 2/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders DYSURIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Renal and urinary disorders URINARY RETENTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders CATARRH	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders EMPHYSEMA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders HIATUS HERNIA	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders PLEURITIC PAIN	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Respiratory, thoracic and mediastinal disorders SLEEP APNOEA SYNDROME	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders EYELID INFECTION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders HAIR COLOUR CHANGES	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders NAIL DISORDER	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders ONYCHOCLASIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders SCAR PAIN	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Skin and subcutaneous tissue disorders STASIS DERMATITIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Surgical and medical procedures ASTRINGENT THERAPY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Surgical and medical procedures GASTROOESOPHAGEAL REFLUX PROPHYLAXIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Surgical and medical procedures VITRECTOMY	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders ANEURYSM	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders AORTIC ANEURYSM	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders HYPERTENSIVE CRISIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders INTERMITTENT CLAUDICATION	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders PERIPHERAL COLDNESS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).
Vascular disorders VENOUS THROMBOSIS	0.00% 0/41 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).	3.2% 1/31 • Adverse events were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years). Any signs or symptoms were collected from first dose through the end of the study (core and follow-up phases), including all visits up to the follow-up database lock (approximately 16 years).

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER