Trial Outcomes & Findings for NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer (NCT NCT01816594)

NCT ID: NCT01816594

Last Updated: 2019-11-14

Results Overview

Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast \[ypT0\]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 50 participants
• Primary outcome timeframe: After 6 weeks
• Results posted on: 2019-11-14

Participant Flow

Planned: Minimum 128 patients (in case of early stopping of both cohorts), maximum: 220 patients (if both cohorts would have proceeded into stage 2), and 174 patients if one cohort would have stopped early.

Screened: 68 patients Randomized and analyzed (safety and efficacy): 50 patients

Participant milestones

Measure	Trastuzumab + BKM120 + Paclitaxel BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Study STARTED	25	25
Overall Study Randomized to the wt Cohort	21	21
Overall Study Randomized to the mt Cohort	4	4
Overall Study COMPLETED	14	23
Overall Study NOT COMPLETED	11	2

Reasons for withdrawal

Measure	Trastuzumab + BKM120 + Paclitaxel BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Study Local Progress	0	2
Overall Study Adverse Event	9	0
Overall Study Withdrawal by Subject	1	0
Overall Study Physician Decision	1	0

Baseline Characteristics

NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer

Baseline characteristics by cohort

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel	Total n=50 Participants Total of all reporting groups
Age, Continuous	51.1 Years STANDARD_DEVIATION 11.5 • n=5 Participants	51.3 Years STANDARD_DEVIATION 11.2 • n=7 Participants	51.2 Years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/white	21 participants n=5 Participants	24 participants n=7 Participants	45 participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: After 6 weeks

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants	32.0 Percentage of participants Interval 14.9 to 53.5	40.0 Percentage of participants Interval 21.1 to 61.3

PRIMARY outcome

Timeframe: After 6 weeks

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=21 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=21 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)	33.3 Percentage of participants Interval 14.6 to 57.0	42.9 Percentage of participants Interval 21.8 to 66.0

PRIMARY outcome

Timeframe: After 6 weeks

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=4 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=4 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)	25.0 Percentage of participants Interval 0.6 to 80.6	25.0 Percentage of participants Interval 0.6 to 80.6

SECONDARY outcome

Timeframe: After week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants	56.0 Percentage of participants Interval 34.9 to 75.6	44.0 Percentage of participants Interval 24.4 to 65.1

SECONDARY outcome

Timeframe: After week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=21 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=21 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants	61.9 Percentage of participants Interval 38.4 to 81.9	42.9 Percentage of participants Interval 21.8 to 66.0

SECONDARY outcome

Timeframe: After week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=4 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=4 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants	25.0 Percentage of participants Interval 0.6 to 80.6	50.0 Percentage of participants Interval 6.8 to 93.2

SECONDARY outcome

Timeframe: 18 weeks

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS)

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Rate of Breast Conserving Surgery (Most Radical Surgery)	60.0 Percentage of participants Interval 38.7 to 78.9	68.0 Percentage of participants Interval 46.5 to 85.1

SECONDARY outcome

Timeframe: After Week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Rate of pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]). If patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to NSABP guidelines.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition	20.0 Percentage of participants Interval 6.8 to 40.7	28.0 Percentage of participants Interval 12.1 to 49.4

SECONDARY outcome

Timeframe: After Week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Rate of pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If a patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition	32.0 Percentage of participants Interval 14.9 to 53.5	36.0 Percentage of participants Interval 18.0 to 57.5

SECONDARY outcome

Timeframe: prior to surgery

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Number of Overall objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Overall Objective Response Rate (ORR) Prior to Surgery for All Participants	56.0 Percentage of participants Interval 34.9 to 75.6	76.0 Percentage of participants Interval 54.9 to 90.6

SECONDARY outcome

Timeframe: After Week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=16 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=15 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)	31.3 Percentage of participants Interval 11.0 to 58.7	26.7 Percentage of participants Interval 7.8 to 55.1

SECONDARY outcome

Timeframe: After Week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=9 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=10 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)	33.3 Percentage of participants Interval 7.5 to 70.1	60.0 Percentage of participants Interval 26.2 to 87.8

SECONDARY outcome

Timeframe: After Week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=16 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=15 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)	68.8 Percentage of participants Interval 41.3 to 89.0	33.3 Percentage of participants Interval 11.8 to 61.6

SECONDARY outcome

Timeframe: After Week 6

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=9 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=10 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-)	33.3 Percentage of participants Interval 7.5 to 70.1	60.0 Percentage of participants Interval 26.2 to 87.8

SECONDARY outcome

Timeframe: 18 weeks

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

This included participants at definitive surgery irrespective of lymph node status

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)	12.0 Percentage of participants Interval 2.5 to 31.2	12.0 Percentage of participants Interval 2.5 to 31.2

SECONDARY outcome

Timeframe: 18 weeks

Population: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.

Outcome measures

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 Participants BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 Participants BKM120 placebo in combination with trastuzumab and paclitaxel
Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)	52.0 Percentage of participants Interval 31.3 to 72.2	60.0 Percentage of participants Interval 38.7 to 78.9

Adverse Events

Trastuzumab + BKM120 + Paclitaxel

Serious events: 8 serious events

Other events: 21 other events

Deaths: 0 deaths

Trastuzumab + BKM120 PBO + Paclitaxel

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 participants at risk BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 participants at risk BKM120 placebo in combination with trastuzumab and paclitaxel
Gastrointestinal disorders Diarrhoea	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
General disorders Catheter site pain	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
General disorders Pyrexia	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
General disorders Thrombosis in device	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Hepatobiliary disorders Hepatotoxicity	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Immune system disorders Hypersensitivity	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Infections and infestations Acute sinusitis	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Infections and infestations Pneumonia	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Hepatic enzyme increased	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Nervous system disorders Headache	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Psychiatric disorders Mental disorder	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.

Other adverse events

Measure	Trastuzumab + BKM120 + Paclitaxel n=25 participants at risk BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.	Trastuzumab + BKM120 PBO + Paclitaxel n=25 participants at risk BKM120 placebo in combination with trastuzumab and paclitaxel
Investigations Increased GGT	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Blood and lymphatic system disorders Anemia	68.0% 17/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	72.0% 18/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Blood and lymphatic system disorders Leukopenia	44.0% 11/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	60.0% 15/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Blood and lymphatic system disorders Lymphopenia	44.0% 11/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Blood and lymphatic system disorders Neutropenia	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	36.0% 9/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Blood and lymphatic system disorders Thrombopenia	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Cardiac disorders Cardiac disorders not yet listed	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Ear and labyrinth disorders Ear and labyrinth disorders	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Eye disorders Eye disorders	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Abdominal pain	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Constipation	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Diarrhea	60.0% 15/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	40.0% 10/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Dysgeusia	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Dyspepsia	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Mucositis	76.0% 19/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	48.0% 12/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Nausea	44.0% 11/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Other gastrointestinal disorders	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Upper abdominal pain	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Gastrointestinal disorders Vomiting	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
General disorders Chills	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
General disorders Fatigue	52.0% 13/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	56.0% 14/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
General disorders Oedema	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
General disorders Other general disorders and administration site conditions	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Immune system disorders Allergic reactions	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Infections and infestations Fever without neutropenia	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Infections and infestations Infection	48.0% 12/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	76.0% 19/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Injury, poisoning and procedural complications Injury and poisoning and procedural complications	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Decreased calcium	36.0% 9/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	44.0% 11/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Decreased potassium	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Decreased serum albumin	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Decreased sodium	36.0% 9/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased ALT	84.0% 21/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	72.0% 18/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased AP	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased AST	76.0% 19/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	36.0% 9/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased FPG	52.0% 13/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased aPTT	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased potassium	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	44.0% 11/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased serum creatinine	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased sodium	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased total bilirubin	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased total cholesterol	56.0% 14/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	56.0% 14/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased triglycerides	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Investigations Increased uric acid	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	40.0% 10/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Metabolism and nutrition disorders Anorexia	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Musculoskeletal and connective tissue disorders Arthralgia	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	40.0% 10/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Musculoskeletal and connective tissue disorders Bone pain	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Musculoskeletal and connective tissue disorders Myalgia	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Musculoskeletal and connective tissue disorders Other musculo-skeletal and connective tissue disorders	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Nervous system disorders Dizziness	36.0% 9/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Nervous system disorders Headache	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Nervous system disorders Other neurological disorder	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Nervous system disorders Peripheral sensory neuropathy	56.0% 14/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	64.0% 16/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Psychiatric disorders Anxiety	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Psychiatric disorders Depression	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Psychiatric disorders Insomnia	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Psychiatric disorders Psychiatric disorders	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Renal and urinary disorders Renal and urinary disorders	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Reproductive system and breast disorders Reproductive system and breast disorders	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	8.0% 2/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Respiratory, thoracic and mediastinal disorders Other respiratory and mediastinal disorders	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	24.0% 6/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Alopecia	72.0% 18/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	68.0% 17/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Dry skin	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	16.0% 4/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Erythema	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Nail disorder	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Other skin and subcutaneous tissue disorders	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Pruritus	40.0% 10/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	60.0% 15/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	48.0% 12/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Skin and subcutaneous tissue disorders Rash other than macular-papular or NOS	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	32.0% 8/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Vascular disorders Hot flushes	20.0% 5/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	28.0% 7/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.
Vascular disorders Vascular disorders	4.0% 1/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.	12.0% 3/25 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: trialandresults.registries@novartis.com

Results disclosure agreements

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

Restriction type: OTHER