Trial Outcomes & Findings for Everolimus Roll-over Protocol for Patients Who Have Completed a Previous Novartis-sponsored Everolimus Study. (NCT NCT01789281)

NCT ID: NCT01789281

Last Updated: 2021-06-11

Results Overview

Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. All SAEs were captured in safety database from enrollment. Safety data collection was changed in the protocol amendment released in March 2016: AEs and SAEs were captured in the clinical database from protocol amendment release (18 March 2016). Hence, SAEs from both safety database and clinical database are summarized separately.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 34 participants
• Primary outcome timeframe: SAEs collected in safety database from enrollment to end of treatment (EOT) plus 30 days, up to approximately 7.2 years. AEs/SAEs collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years
• Results posted on: 2021-06-11

Participant Flow

There was no screening period. Patients enrolled into trial directly from the parent protocol.

Participant milestones

Measure	Everolimus Participants who were receiving everolimus in a Novartis-sponsored study	Everolimus+Sandostatin LAR Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study
Overall Study STARTED	22	12
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	22	10

Reasons for withdrawal

Measure	Everolimus Participants who were receiving everolimus in a Novartis-sponsored study	Everolimus+Sandostatin LAR Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study
Overall Study Disease progression	15	4
Overall Study Adverse Event	5	5
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	1	0
Overall Study Administrative problems	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Everolimus n=22 Participants Participants who were receiving everolimus in a Novartis-sponsored study	Everolimus+Sandostatin LAR n=12 Participants Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study	Total n=34 Participants Total of all reporting groups
Age, Continuous	58.6 Years STANDARD_DEVIATION 9.52 • n=22 Participants	57.9 Years STANDARD_DEVIATION 11.30 • n=12 Participants	58.4 Years STANDARD_DEVIATION 10.02 • n=34 Participants
Sex: Female, Male Female	9 Participants n=22 Participants	6 Participants n=12 Participants	15 Participants n=34 Participants
Sex: Female, Male Male	13 Participants n=22 Participants	6 Participants n=12 Participants	19 Participants n=34 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: SAEs collected in safety database from enrollment to end of treatment (EOT) plus 30 days, up to approximately 7.2 years. AEs/SAEs collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years

Population: All subjects who received at least one dose of everolimus after enrolling into the roll-over study.

Any sign or symptom that occurs during the study treatment plus the 30 days post treatment. All SAEs were captured in safety database from enrollment. Safety data collection was changed in the protocol amendment released in March 2016: AEs and SAEs were captured in the clinical database from protocol amendment release (18 March 2016). Hence, SAEs from both safety database and clinical database are summarized separately.

Outcome measures

Measure	Everolimus n=22 Participants Participants who were receiving everolimus in a Novartis-sponsored study	Everolimus+Sandostatin LAR n=12 Participants Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs (Safety database)	6 Participants	9 Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment-related SAEs (Safety database)	1 Participants	4 Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs (Clinical Database)	7 Participants	7 Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Tretament-related AEs (Clinical Database)	4 Participants	4 Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs (Clinical Database)	2 Participants	4 Participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment-related SAEs (Clinical Database)	0 Participants	2 Participants

SECONDARY outcome

Timeframe: After 3 months from enrollment, every 3 months, until end of treatment, assessed up to 7.2 years

Population: All participants who remained in the study after protocol amendment (18 March 2016) with at least one assessment reported for the specified endpoint

Percentage of patients with clinical benefit as judged by the investigator. Investigator attestation of continued clinical benefit was collected in clinical database after protocol amendment (release date 18 March 2016). Clinical benefit assessment before protocol amendment was done retrospectively.

Outcome measures

Measure	Everolimus n=9 Participants Participants who were receiving everolimus in a Novartis-sponsored study	Everolimus+Sandostatin LAR n=7 Participants Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study
Percentage of Patients With Clinical Benefit At 3 months	9 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 6 months	8 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 9 months	8 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 12 months	8 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 15 months	8 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 18 months	8 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 21 months	8 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 24 months	6 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 27 months	5 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 30 months	3 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 33 months	2 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 36 months	1 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 39 months	1 Participants	7 Participants
Percentage of Patients With Clinical Benefit At 42 months	1 Participants	6 Participants
Percentage of Patients With Clinical Benefit At 45 months	1 Participants	6 Participants
Percentage of Patients With Clinical Benefit At 48 months	1 Participants	6 Participants
Percentage of Patients With Clinical Benefit At 51 months	1 Participants	6 Participants
Percentage of Patients With Clinical Benefit At 54 months	0 Participants	6 Participants
Percentage of Patients With Clinical Benefit At 57 months	0 Participants	5 Participants
Percentage of Patients With Clinical Benefit At 60 months	0 Participants	5 Participants
Percentage of Patients With Clinical Benefit At 63 months	0 Participants	4 Participants
Percentage of Patients With Clinical Benefit At 66 months	0 Participants	4 Participants
Percentage of Patients With Clinical Benefit At 69 months	0 Participants	3 Participants
Percentage of Patients With Clinical Benefit At 72 months	0 Participants	3 Participants
Percentage of Patients With Clinical Benefit At 75 months	0 Participants	3 Participants
Percentage of Patients With Clinical Benefit At 78 months	0 Participants	2 Participants
Percentage of Patients With Clinical Benefit At 81 months	0 Participants	1 Participants
Percentage of Patients With Clinical Benefit At 84 months	0 Participants	0 Participants

Adverse Events

Everolimus

Serious events: 6 serious events

Other events: 3 other events

Deaths: 1 deaths

Everolimus + Sandostatin LAR

Serious events: 9 serious events

Other events: 5 other events

Deaths: 2 deaths

All Subjects

Serious events: 15 serious events

Other events: 8 other events

Deaths: 3 deaths

Serious adverse events

Measure	Everolimus n=22 participants at risk Participants who were receiving everolimus in a Novartis-sponsored study	Everolimus + Sandostatin LAR n=12 participants at risk Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study	All Subjects n=34 participants at risk All subjects
Blood and lymphatic system disorders Aplastic anaemia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Cardiac disorders Atrial fibrillation	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Cardiac disorders Cardiac failure congestive	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Cardiac disorders Heart valve incompetence	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Abdominal pain	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Ileus	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Nausea	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Umbilical hernia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
General disorders Asthenia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Staphylococcal infection	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Hepatobiliary disorders Jaundice	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	0.00% 0/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Clostridium difficile infection	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Pneumonia	9.1% 2/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	25.0% 3/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	14.7% 5/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Pyelonephritis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Urinary tract infection	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Fluid intake reduced	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Malnutrition	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Musculoskeletal and connective tissue disorders Arthralgia	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	0.00% 0/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	0.00% 0/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	0.00% 0/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Nervous system disorders Cerebrovascular accident	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Nervous system disorders Hepatic encephalopathy	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	0.00% 0/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Nervous system disorders Metabolic encephalopathy	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	0.00% 0/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Renal and urinary disorders Acute kidney injury	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Renal and urinary disorders Nephropathy	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Skin and subcutaneous tissue disorders Petechiae	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Vascular disorders Deep vein thrombosis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Vascular disorders Haemorrhage	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.

Other adverse events

Measure	Everolimus n=22 participants at risk Participants who were receiving everolimus in a Novartis-sponsored study	Everolimus + Sandostatin LAR n=12 participants at risk Participants who were receiving everolimus in combination with Sandostatin LAR depot in a Novartis-sponsored study	All Subjects n=34 participants at risk All subjects
Blood and lymphatic system disorders Anaemia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Cardiac disorders Cardiac ventricular thrombosis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Eye disorders Periorbital oedema	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Abdominal distension	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Abdominal pain	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	25.0% 3/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.8% 3/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Diarrhoea	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Duodenal stenosis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Dyspepsia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Nausea	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Stomatitis	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Gastrointestinal disorders Vomiting	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
General disorders Fatigue	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
General disorders Oedema peripheral	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
General disorders Pain	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Clostridium difficile infection	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Pneumonia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Sinusitis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Infections and infestations Urinary tract infection	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Injury, poisoning and procedural complications Contusion	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Investigations Blood chromogranin A increased	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Investigations Blood triglycerides increased	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Investigations Weight decreased	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Vitamin B12 deficiency	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Nervous system disorders Headache	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	16.7% 2/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Psychiatric disorders Depression	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Psychiatric disorders Insomnia	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Respiratory, thoracic and mediastinal disorders Cough	4.5% 1/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Respiratory, thoracic and mediastinal disorders Pneumonitis	9.1% 2/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	0.00% 0/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	5.9% 2/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/22 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	8.3% 1/12 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.	2.9% 1/34 • SAEs were collected in safety database from enrollment to end of the treatment (EOT) plus 30 days, up to approximately 7.2 years. Other AEs (Non-serious AEs) were collected in clinical database from protocol amendment date 18 March 2016 to EOT plus 30 days, up to approximately 4.5 years Any sign or symptom that occurs during the study treatment plus 30 days post treatment. SAEs were collected throughout the study duration in the safety database. Other AEs (Non-serious AEs) were collected after global protocol amendment date 18-Mar-2016 in the clinical database.

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 (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER