Trial Outcomes & Findings for A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi (NCT NCT01633060)

Last Updated: 2019-01-30

Results Overview

Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm. Patients were followed up for approximately every 6 weeks after randomization.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

432 participants

Primary outcome timeframe

Every 6 weeks after randomization up to a maximum of 4 years

Results posted on

2019-01-30

Participant Flow

This study was conducted at 201 centers in 22 countries worldwide (Argentina, Austria, Belgium, Bulgaria, Canada, Colombia, Finland, France, Germany, Greece, Hungary, Italy, Republic of Korea, Lebanon, The Netherlands, Norway, Poland, Spain, Sweden, Thailand, UK and USA).

At least 420 patients were planned to be enrolled, randomized in a 2:1 ratio (two buparlisib, one placebo). A total of 432 patients were actually enrolled and analyzed (buparlisib arm: N=289; placebo arm: N=143). Not completed: in Randomization Phase=Randomized and not Treated; in Treatment Phase=Discontinued study treatment per Protocol.

Participant milestones

Participant milestones
Measure	BKM120 100mg + Fulvestrant BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Randomization Phase STARTED	289	143
Randomization Phase COMPLETED	288	140
Randomization Phase NOT COMPLETED	1	3
Treatment Phase STARTED	288	140
Treatment Phase FAS - ctDNA PIK3CA Mutant	100	35
Treatment Phase FAS - ctDNA PIK3CA Non-mutant	132	81
Treatment Phase Safety Set (SS)	288	140
Treatment Phase Pharmacokinetic Analysis Set (PAS)	63	0
Treatment Phase COMPLETED	0	0
Treatment Phase NOT COMPLETED	288	140
Post-Treatment Efficacy Follow-Up Phase STARTED	16	2
Post-Treatment Efficacy Follow-Up Phase COMPLETED	0	0
Post-Treatment Efficacy Follow-Up Phase NOT COMPLETED	16	2

Reasons for withdrawal

Reasons for withdrawal
Measure	BKM120 100mg + Fulvestrant BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Randomization Phase Protocol deviation	1	2
Randomization Phase Technical problem	0	1
Treatment Phase Adverse Event	24	3
Treatment Phase Lost to Follow-up	1	0
Treatment Phase Physician Decision	16	7
Treatment Phase Progressive Disease	210	120
Treatment Phase Protocol Deviation	1	0
Treatment Phase Study Terminated by sponsor	7	3
Treatment Phase Subject/guardian decision	25	4
Treatment Phase Death	4	3
Post-Treatment Efficacy Follow-Up Phase Adverse Event	2	0
Post-Treatment Efficacy Follow-Up Phase Physician Decision	1	0
Post-Treatment Efficacy Follow-Up Phase Progressive Disease	10	1
Post-Treatment Efficacy Follow-Up Phase Study terminated by sponsor	1	0
Post-Treatment Efficacy Follow-Up Phase Subject/Guardian Decision	1	1
Post-Treatment Efficacy Follow-Up Phase Death	1	0

Baseline Characteristics

Full Analysis Set (FAS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.	Total n=432 Participants Total of all reporting groups
Age, Continuous	60.5 Years STANDARD_DEVIATION 9.76 • n=93 Participants • Full Analysis Set (FAS)	61.5 Years STANDARD_DEVIATION 9.23 • n=4 Participants • Full Analysis Set (FAS)	60.8 Years STANDARD_DEVIATION 9.59 • n=27 Participants • Full Analysis Set (FAS)
Sex: Female, Male Female	289 Participants n=93 Participants • Full Analysis Set (FAS)	143 Participants n=4 Participants • Full Analysis Set (FAS)	432 Participants n=27 Participants • Full Analysis Set (FAS)
Sex: Female, Male Male	0 Participants n=93 Participants • Full Analysis Set (FAS)	0 Participants n=4 Participants • Full Analysis Set (FAS)	0 Participants n=27 Participants • Full Analysis Set (FAS)
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=93 Participants • Full Analysis Set (FAS)	1 Participants n=4 Participants • Full Analysis Set (FAS)	5 Participants n=27 Participants • Full Analysis Set (FAS)
Race (NIH/OMB) Asian	20 Participants n=93 Participants • Full Analysis Set (FAS)	9 Participants n=4 Participants • Full Analysis Set (FAS)	29 Participants n=27 Participants • Full Analysis Set (FAS)
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants • Full Analysis Set (FAS)	0 Participants n=4 Participants • Full Analysis Set (FAS)	0 Participants n=27 Participants • Full Analysis Set (FAS)
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants • Full Analysis Set (FAS)	4 Participants n=4 Participants • Full Analysis Set (FAS)	8 Participants n=27 Participants • Full Analysis Set (FAS)
Race (NIH/OMB) White	249 Participants n=93 Participants • Full Analysis Set (FAS)	121 Participants n=4 Participants • Full Analysis Set (FAS)	370 Participants n=27 Participants • Full Analysis Set (FAS)
Race (NIH/OMB) More than one race	0 Participants n=93 Participants • Full Analysis Set (FAS)	0 Participants n=4 Participants • Full Analysis Set (FAS)	0 Participants n=27 Participants • Full Analysis Set (FAS)
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=93 Participants • Full Analysis Set (FAS)	8 Participants n=4 Participants • Full Analysis Set (FAS)	20 Participants n=27 Participants • Full Analysis Set (FAS)

PRIMARY outcome

Timeframe: Every 6 weeks after randomization up to a maximum of 4 years

Population: Full Analysis Set (FAS) based on Primary Analysis.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Progression Free Survival (PFS) Based on Local Investigator Assessment - Full Analysis Set (FAS)	3.9 Months Interval 2.8 to 4.2	1.8 Months Interval 1.5 to 2.8

SECONDARY outcome

Timeframe: Every 6 weeks after randomization up to a maximum of 5 years

Population: Full Analysis Set (FAS) based on Primary Analysis.

Overall Survival (OS) is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Survival (OS) - Full Analysis Set (FAS)	21.2 Months Interval 18.2 to 23.4	22.1 Months Interval 17.3 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)

SECONDARY outcome

Timeframe: Every 6 weeks after randomization up to a maximum of 5 years

Population: Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Progression Free Survival (PFS) by PIK3CA Mutational Status FAS ctDNA PIK3CA mutant	4.2 Months Interval 2.8 to 6.7	1.6 Months Interval 1.4 to 2.8
Progression Free Survival (PFS) by PIK3CA Mutational Status FAS ctDNA PIK3CA non-mutant	3.9 Months Interval 2.8 to 4.3	2.7 Months Interval 1.5 to 3.6

SECONDARY outcome

Timeframe: Every 6 weeks after randomization up to a maximum of 5 years

Population: Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.

Overall Survival (OS) by PIK3CA mutational status based on ctDNA is defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last known date patient alive. Patients were followed up approximately every 6 weeks after randomization and every 3 months during survival follow-up.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Survival (OS) by PIK3CA Mutational Status FAS ctDNA PIK3CA mutant	21.8 Months Interval 14.7 to 25.8	NA Months Interval 14.5 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)
Overall Survival (OS) by PIK3CA Mutational Status FAS ctDNA PIK3CA non-mutant	21.4 Months Interval 17.3 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)	21.4 Months Interval 17.3 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)

SECONDARY outcome

Timeframe: Every 6 weeks after randomization up to a maximum of 5 years

Population: Full Analysis Set (FAS), Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.

Overall Response Rate (ORR) is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. ORR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target/non target lesions: Complete Response (CR), disappearance of all target/non target lesions (all lymph nodes assigned as non-target lesions must be non-pathological in size (\< 10 mm short axis)); Partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions ; Overall Response (OR)= CR+PR. Patients were followed up for the duration of the study and for approximately every 6 weeks after randomization.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Overall Response Rate (ORR) by PIK3CA Mutational Status Full Analysis Set (FAS)	7.6 Percentage of Participants Interval 4.8 to 11.3	2.1 Percentage of Participants Interval 0.4 to 6.0
Overall Response Rate (ORR) by PIK3CA Mutational Status FAS ctDNA PIK3CA mutant	10.0 Percentage of Participants Interval 4.9 to 17.6	0 Percentage of Participants Interval 0.0 to 10.0
Overall Response Rate (ORR) by PIK3CA Mutational Status FAS ctDNA PIK3CA non-mutant	7.6 Percentage of Participants Interval 3.7 to 13.5	3.7 Percentage of Participants Interval 0.8 to 10.4

SECONDARY outcome

Timeframe: Week 14, Week 24

Population: Full Analysis Set (FAS), Full Analysis Set (FAS) -ctDNA PIK3CA mutant, Full Analysis Set (FAS) - ctDNA PIK3CA non-mutant based on Primary Analysis.

Clinical Benefit Rate (CBR) is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) or Non-CR/non-PD lasting more than 14 or 24 weeks based on local investigator's assessment according to RECIST 1.1. CBR was analyzed in the full population and by PIK3CA mutational status based on ctDNA. Patients were followed up for the duration of the study and approximately every 6 weeks after randomization.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status CBR>=24wks(FAS)	24.6 Percentage of Participants Interval 19.7 to 29.9	15.4 Percentage of Participants Interval 9.9 to 22.4
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status CBR>=14wks(FAS ctDNA PIK3CA mutant)	38.0 Percentage of Participants Interval 28.5 to 48.3	14.3 Percentage of Participants Interval 4.8 to 30.3
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status CBR>=14wks(FAS)	33.2 Percentage of Participants Interval 27.8 to 39.0	20.3 Percentage of Participants Interval 14.0 to 27.8
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status CBR>=24wks(FAS ctDNA PIK3CA mutant)	30.0 Percentage of Participants Interval 21.2 to 40.0	11.4 Percentage of Participants Interval 3.2 to 26.7
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status CBR>=14wks(FAS ctDNA PIK3CA non-mutant)	36.4 Percentage of Participants Interval 28.2 to 45.2	21.0 Percentage of Participants Interval 12.7 to 31.5
Clinical Benefit Rate (CBR) by PIK3CA Mutational Status CBR>= 24wks(FAS ctDNA PIK3CA non-mutant)	25.8 Percentage of Participants Interval 18.5 to 34.1	14.8 Percentage of Participants Interval 7.9 to 24.4

SECONDARY outcome

Timeframe: From first dose of study treatment to 30 days after last dose of study treatment, up to 5 years

Population: Safety Set (SS) based on Final Analysis

Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=288 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=140 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS) AEs	97.9 Percentage of Participants	92.9 Percentage of Participants
Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS) SAEs	25.7 Percentage of Participants	18.6 Percentage of Participants
Long-term Safety and Tolerability in the Two Treatment Arms - Safety Set (SS) Deaths	42.7 Percentage of Participants	48.6 Percentage of Participants

SECONDARY outcome

Timeframe: C1D1 1 hour post dose, C1D1 2 hour post dose, C1D1 6 hour post dose and C1D1 9 hour post dose

Population: Pharmacokinetic Analysis Set (PAS) based on Primary Analysis

Plasma samples were collected from the first 100 BKM120-treated patients on Cycle 1 Day 1 (at 1h, 2h, and 6h post-dose and a recommended 9h post-dose sample).

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=63 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS) C1D1 - 1 hour post dose	425.178 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 149.6	—
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS) C1D1 - 2 hour post dose	615.441 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 70.9	—
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS) C1D1 - 6 hour post dose	314.094 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 41.9	—
Plasma Concentration-time Profiles of BKM120 in Combination With Fulvestrant at Cycle 1 Day 1 - Pharmacokinetic Analysis Set (PAS) C1D1 - 9 hour post dose	302.899 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 58.3	—

SECONDARY outcome

Timeframe: C1D15, C2D1, C3D1 and C4D1

Population: Pharmacokinetic Analysis Set (PAS) based on Primary Analysis

Pre-dose samples were collected for trough concentrations at Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1 and Cycle 4 Day 1.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=63 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) C1D15	939.978 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 36.8	—
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) C2D1	880.074 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 38.4	—
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) C3D1	777.026 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 131.0	—
Predose Trough Concentration-time Profile of BKM120 in Combination With Fulvestrant Over Time - Pharmacokinetic Analysis Set (PAS) C4D1	1088.074 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 27.0	—

SECONDARY outcome

Timeframe: Baseline, Week 6 (C2D15), Week 12 (C4D1), then every 8 weeks until discontinuation (a cycle [C] = 4 weeks) up to 5 years.

Population: Full Analysis (FAS) based on Primary Analysis

The global health status/QoL scale score of the QLQ-C30 is identified as the primary PRO variable of interest. Physical Functioning (PF), Emotional Functioning (EF) and Social Functioning (SF) scale scores of the QLQ-C30. The time to definitive 10% deterioration is defined as the time from the randomization date to the date of an event, which is defined as a worsening (decrease) in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study or death due to any cause. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high /healthy level of functioning, a high score for the global health status / QoL represents a high QoL.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS) EORTC QLQ-30 - PF scale score	11.8 Months Interval 8.1 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)	10.1 Months Interval 7.5 to 14.6
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS) EORTC QLQ-30 - SF scale score	10.0 Months Interval 6.2 to 20.2	11.5 Months Interval 6.4 to 14.6
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS) EORTC QLQ-30 - Global QoL score	5.3 Months Interval 4.4 to 8.1	6.3 Months Interval 3.0 to 9.9
Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 - Full Analysis Set (FAS) EORTC QLQ-30 - EF scale score	10.0 Months Interval 6.2 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)	10.0 Months Interval 4.9 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)

SECONDARY outcome

Timeframe: Screening, Baseline (Cycle 1 Day 1) and then at day 1 of each cycle and at the EOT visit

Population: Full Analysis (FAS) based on Primary Analysis

The Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale used to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. The ECOG Performance Scores has 5 grades: 0 = fully active, able to carry on all pre-disease performance without restriction, 1 = restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work, 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours, 3 = capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4 = completely disabled, cannot carry on any self-care, totally confined to bed or chair and 5 = dead. Definitive deterioration is defined as no improvement in the ECOG status following observation of the deterioration.

Outcome measures

Outcome measures
Measure	BKM120 100mg + Fulvestrant n=289 Participants BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol.	Placebo + Fulvestrant n=143 Participants BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.
Time to Definitive Deterioration of ECOG Performance Status From Baseline - Full Analysis Set (FAS)	18.3 Months Interval 6.9 to NA: Not estimable (preliminary OS analyses). Final OS analyses not done due to early study termination (OS data collection stopped early)	12.0 Months Interval 6.4 to 14.2

Adverse Events

BKM120 100 mg + Fulvestrant

Serious events: 74 serious events

Other events: 271 other events

Deaths: 123 deaths

Placebo + Fulvestrant

Serious events: 26 serious events

Other events: 113 other events

Deaths: 68 deaths

All Patients

Serious events: 100 serious events

Other events: 384 other events

Deaths: 191 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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

Serious adverse events
Measure	BKM120 100 mg + Fulvestrant n=288 participants at risk BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol test.	Placebo + Fulvestrant n=140 participants at risk BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.	All Patients n=428 participants at risk All Patients
Blood and lymphatic system disorders Anaemia	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.47% 2/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Febrile neutropenia	0.69% 2/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.47% 2/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Blood and lymphatic system disorders Haemolytic anaemia	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Angina pectoris	0.69% 2/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.47% 2/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Atrial fibrillation	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Cardiac arrest	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Cardiac failure acute	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Cardiac tamponade	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Intracardiac mass	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Cardiac disorders Pericardial effusion	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Ear and labyrinth disorders Vertigo	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Eye disorders Amaurosis	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Eye disorders Diplopia	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Eye disorders Eyelid ptosis	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Eye disorders Optic atrophy	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Eye disorders Vision blurred	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal pain	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.47% 2/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Ascites	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Diarrhoea	1.0% 3/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.93% 4/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Haematemesis	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Ileus	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Intestinal perforation	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Nausea	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.4% 2/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.70% 3/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Oesophageal haemorrhage	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Vomiting	1.4% 4/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.2% 5/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Asthenia	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Death	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Facial pain	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Fatigue	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.47% 2/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders General physical health deterioration	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Malaise	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Non-cardiac chest pain	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Pyrexia	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.4% 2/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.47% 2/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.71% 1/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Hepatobiliary disorders Bile duct stenosis	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Hepatobiliary disorders Hepatic function abnormal	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Hepatobiliary disorders Hepatotoxicity	0.69% 2/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.47% 2/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Hepatobiliary disorders Jaundice	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Clostridial infection	0.35% 1/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.23% 1/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Other adverse events
Measure	BKM120 100 mg + Fulvestrant n=288 participants at risk BKM120 100 mg per day and fulvestrant given until progression or as described in the protocol test.	Placebo + Fulvestrant n=140 participants at risk BKM120 matching placebo daily and fulvestrant given until progression or as described in the protocol.	All Patients n=428 participants at risk All Patients
Gastrointestinal disorders Abdominal pain	5.6% 16/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.3% 6/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.1% 22/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Abdominal pain upper	8.0% 23/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.9% 4/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.3% 27/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Constipation	10.1% 29/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.3% 13/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.8% 42/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Diarrhoea	26.4% 76/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.3% 13/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	20.8% 89/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Dry mouth	8.0% 23/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	3.6% 5/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.5% 28/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Dyspepsia	10.1% 29/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.4% 2/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.2% 31/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Nausea	34.7% 100/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	17.1% 24/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	29.0% 124/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Stomatitis	11.1% 32/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.3% 6/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	8.9% 38/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Gastrointestinal disorders Vomiting	9.4% 27/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.3% 13/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.3% 40/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Asthenia	18.1% 52/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.7% 15/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	15.7% 67/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Fatigue	24.0% 69/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	17.9% 25/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	22.0% 94/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Oedema peripheral	6.2% 18/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.4% 2/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.7% 20/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
General disorders Pyrexia	6.9% 20/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.7% 8/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.5% 28/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Infections and infestations Urinary tract infection	5.2% 15/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.1% 3/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.2% 18/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Alanine aminotransferase increased	39.2% 113/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.1% 10/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	28.7% 123/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Aspartate aminotransferase increased	37.5% 108/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.0% 14/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	28.5% 122/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Gamma-glutamyltransferase increased	9.0% 26/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	3.6% 5/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.2% 31/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Investigations Weight decreased	9.4% 27/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.0% 7/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.9% 34/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Decreased appetite	16.3% 47/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.4% 9/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	13.1% 56/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Metabolism and nutrition disorders Hyperglycaemia	36.1% 104/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.9% 4/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	25.2% 108/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 21/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	8.6% 12/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.7% 33/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Back pain	9.4% 27/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.9% 11/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	8.9% 38/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Bone pain	3.1% 9/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.9% 11/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.7% 20/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Muscle spasms	7.3% 21/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	3.6% 5/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.1% 26/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Musculoskeletal and connective tissue disorders Pain in extremity	6.6% 19/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.1% 10/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.8% 29/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Dizziness	12.2% 35/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.1% 10/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.5% 45/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Dysgeusia	6.6% 19/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.9% 4/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.4% 23/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Headache	9.4% 27/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.7% 15/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.8% 42/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Nervous system disorders Tremor	6.2% 18/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	0.00% 0/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.2% 18/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Psychiatric disorders Anxiety	17.7% 51/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	10.7% 15/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	15.4% 66/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Psychiatric disorders Depression	20.8% 60/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.9% 11/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	16.6% 71/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Psychiatric disorders Insomnia	9.0% 26/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.9% 11/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	8.6% 37/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Psychiatric disorders Mood altered	5.2% 15/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	1.4% 2/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.0% 17/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Cough	9.4% 27/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.4% 9/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	8.4% 36/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.6% 22/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	8.6% 12/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.9% 34/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Skin and subcutaneous tissue disorders Dry skin	7.6% 22/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.1% 3/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.8% 25/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Skin and subcutaneous tissue disorders Pruritus	8.7% 25/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.9% 4/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	6.8% 29/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Skin and subcutaneous tissue disorders Rash	12.8% 37/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	2.1% 3/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.3% 40/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Vascular disorders Hot flush	3.5% 10/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	7.9% 11/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	4.9% 21/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
Vascular disorders Hypertension	11.5% 33/288 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	5.7% 8/140 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.	9.6% 41/428 • Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment (FPFT) until end of treatment exposure + 30 days safety follow-up. Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.