Trial Outcomes & Findings for Cabazitaxel Versus Docetaxel Both With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer (NCT NCT01308567)

Last Updated: 2019-06-05

Results Overview

OS was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive, or at the cut-off date if the participant's last contact was after the cut-off date. The study cut-off date for the final analysis of OS was the date when the 774th death had been observed. Analysis was performed by Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1168 participants

Primary outcome timeframe

Baseline up to death or study cut-off date, whichever was earlier (maximum duration: 51 months )

Results posted on

2019-06-05

Participant Flow

The study was conducted at 159 centers in 25 countries. A total of 1510 participants were screened between 17 May 2011 and 09 September 2015 of whom 1168 participants were randomized and 342 were considered as screen failures.

A total of 1168 participants randomized in this study. Of these, 21 participants randomized but not treated. These participants were included in intent-to-treat (ITT) population, not in safety population. "Study cut-off date" for outcome measures was up to "primary completion date" (PCD) only. After PCD, only adverse event (AE) data was updated.

Participant milestones

Participant milestones
Measure	Docetaxel 75 mg/m^2 Docetaxel (TXT) 75 mg/m\^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until disease progression (DP), unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Overall Study STARTED	391	389	388
Overall Study Treated	388	382	377
Overall Study COMPLETED	389	385	384
Overall Study NOT COMPLETED	2	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Docetaxel 75 mg/m^2 Docetaxel (TXT) 75 mg/m\^2 intravenous (IV) infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until disease progression (DP), unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Overall Study Lost to Follow-up	2	4	4

Baseline Characteristics

Cabazitaxel Versus Docetaxel Both With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Docetaxel 75 mg/m^2 n=391 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=389 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=388 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Total n=1168 Participants Total of all reporting groups
Age, Customized <65 years	123 Participants n=5 Participants	128 Participants n=7 Participants	125 Participants n=5 Participants	376 Participants n=4 Participants
Age, Customized 65-74 years	181 Participants n=5 Participants	187 Participants n=7 Participants	182 Participants n=5 Participants	550 Participants n=4 Participants
Age, Customized ≥75 years	87 Participants n=5 Participants	74 Participants n=7 Participants	81 Participants n=5 Participants	242 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	391 Participants n=5 Participants	389 Participants n=7 Participants	388 Participants n=5 Participants	1168 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to death or study cut-off date, whichever was earlier (maximum duration: 51 months )

Population: ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=391 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=389 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=388 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Overall Survival (OS)	24.3 months Interval 22.18 to 27.6	24.5 months Interval 21.75 to 27.2	25.2 months Interval 22.9 to 26.97

SECONDARY outcome

Timeframe: Baseline up to tumor progression, PSA progression, pain progression or death (maximum duration: 51 months)

Population: ITT population included all randomized participants.

PFS: time interval between date of randomization to date of first occurrence of any of following events: tumor progression according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; Prostate Specific Antigen (PSA) progression; pain progression or death due to any cause. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=391 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=389 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=388 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Progression Free Survival (PFS)	5.3 months Interval 4.86 to 5.78	4.4 months Interval 3.91 to 5.09	5.1 months Interval 4.6 to 5.72

SECONDARY outcome

Timeframe: Baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Population: ITT population included all randomized participants.

Time to tumor progression free survival was defined as the time interval between randomization and the date of first occurrence of tumor progression (assessed using RECIST version 1.1) or death, whichever was earlier. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=391 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=389 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=388 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Time to Tumor Progression Free Survival	12.1 months Interval 11.3 to 13.77	13.4 months Interval 11.37 to 14.75	13.1 months Interval 11.66 to 14.32

SECONDARY outcome

Timeframe: Baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Population: Analysis was performed on ITT population. Number of participants analyzed=participants with measurable disease at baseline and at least one valid post-baseline value analyzed for specified outcome measure.

Overall objective tumor response was defined as having a partial response (PR) or complete response (CR) according to the RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=175 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=188 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=173 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Percentage of Participants With Overall Objective Tumor Response	30.9 percentage of participants Interval 24.0 to 37.7	32.4 percentage of participants Interval 25.8 to 39.1	41.6 percentage of participants Interval 34.3 to 49.0

SECONDARY outcome

Timeframe: Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Population: Analysis was performed on ITT population which included all randomized participants.

Time to PSA-PFS: time interval between date of randomization \& first occurrence of PSA progression/ death, whichever was earlier. PSA progression:1) In PSA responders(≥50% decline from baseline PSA of ≥10 ng/mL):increase of ≥25%(at least 2 ng/mL)over nadir value, confirmed by second PSA value at least 3 weeks later;2)In PSA non-responders(not achieved ≥50% decline from baseline PSA ≥10 ng/mL):increase of ≥25% (at least 2 ng/mL) over baseline value, confirmed by second PSA value at least 3 weeks later;3)In participants not eligible for PSA response(baseline PSA \<10 ng/mL):(a)in participants with baseline PSA\>0 ng/mL\&\<10 ng/mL: increase in PSA by 25% (at least 2 ng/mL) above baseline level, confirmed by second PSA value at least 3weeks apart;(b)in participants with baseline value=0ng/mL: a post baseline PSA value ≥2ng/mL.Early rise in PSA only indicated progression if it was associated with another sign of DP or if it continued beyond 12 weeks. Analysis performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=391 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=389 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=388 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Time to Prostate Serum Antigen Progression Free Survival (PSA-PFS)	8.3 months Interval 7.66 to 9.2	8.2 months Interval 7.43 to 8.9	9.2 months Interval 8.44 to 9.92

SECONDARY outcome

Timeframe: Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)

Population: Analysis was performed on ITT population. Number of participants analyzed=participants with PSA value ≥10 ng/mL at baseline and at least one valid post-baseline value for specified outcome measure.

PSA response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed by a second PSA value at least 3 weeks later in participants with baseline PSA value ≥10 ng/mL.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=354 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=346 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=342 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Percentage of Participants With PSA Response	68.4 percentage of participants Interval 63.5 to 73.2	60.7 percentage of participants Interval 55.5 to 65.8	68.7 percentage of participants Interval 63.8 to 73.6

SECONDARY outcome

Timeframe: Baseline until disease progression, death or study cut-off date (maximum duration: 51 months)

Population: Analysis was performed on ITT population which included all randomized participants.

Time to pain PFS was defined as the time interval between date of randomization and the date of the first occurrence of pain progression or death, whichever was earlier. Pain progression was defined as an increase of ≥1 point in the median present pain intensity (PPI) score from the nadir confirmed by a second assessment at least 3 weeks later or ≥25 % increase in the mean analgesic score from baseline, due to cancer related pain confirmed by a second assessment at least 3 weeks later or requirement for local palliative radiotherapy. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=391 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=389 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=388 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Time to Pain Progression Free Survival (Pain PFS)	10.1 months Interval 8.28 to 11.76	8.0 months Interval 6.9 to 9.66	7.3 months Interval 6.44 to 9.3

SECONDARY outcome

Timeframe: Baseline until pain progression, death or study cut-off date (maximum duration: 51 months)

Population: Analysis was performed on ITT population. Number of participants analyzed=participants with pain score with median PPI \>= 2 and/or mean analgesic score \>= 10 points at baseline and at least one valid post-baseline value for specified outcome measure.

Pain response was defined as either a ≥2-point decrease from baseline median PPI score without increase in analgesic score, or a ≥50% decrease in analgesic use from baseline mean analgesic score (only in participants with baseline mean analgesic score≥10) without increase in the pain. Either criterion was maintained for 2 consecutive evaluations at least 3 weeks apart. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=81 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=99 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=104 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Percentage of Participants With Pain Response	40.7 percentage of participants Interval 30.0 to 51.4	42.4 percentage of participants Interval 32.7 to 52.2	39.4 percentage of participants Interval 30.0 to 48.8

SECONDARY outcome

Timeframe: Baseline until occurrence of first SRE or death (maximum duration: 51 months)

Population: Analysis was performed on ITT population which included all randomized participants.

SRE free survival was defined as the time interval between the date of randomization and the date of the occurrence of the first event defining a SRE or death due to any cause, whichever was earlier. SRE were assessed by clinical evaluation. Occurrence of SRE was defined as: pathological fracture(s) and/or spinal cord compression; need for bone irradiation, including radioisotopes or bone surgery; and change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the setting of increased pain) to treat bone pain. Analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=391 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=389 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=388 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Skeletal Related Events (SRE) Free Survival	19.0 months Interval 15.24 to 22.44	19.2 months Interval 15.21 to 24.61	17.1 months Interval 14.59 to 20.5

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 (each cycle 21-day); post-treatment follow up 1, 2, 3, 4, 5, 6 (each up to 12 weeks)

Population: Analysis was performed on FACT-P population that included all participants with evaluable individual FACT-P subscale score at baseline and post-baseline on at least 1 of the subscale domains. Here, 'number analyzed' = participants with available data for each specified category.

FACT-P was a 39-item participant rated questionnaire that measures the concerns of participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). FACT-P total score was the sum of all 5 subscale scores. It ranged from 0 to156 with higher score indicated better quality of life with fewer symptoms.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=375 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=370 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=361 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 1	4.17 units on a scale Interval 1.3 to 7.05	7.66 units on a scale Interval 4.79 to 10.53	6.93 units on a scale Interval 3.97 to 9.88
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 2	5.33 units on a scale Interval 2.46 to 8.2	7.15 units on a scale Interval 4.28 to 10.01	5.28 units on a scale Interval 2.32 to 8.24
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 3	4.94 units on a scale Interval 2.06 to 7.82	6.79 units on a scale Interval 3.93 to 9.66	4.61 units on a scale Interval 1.64 to 7.58
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 4	4.07 units on a scale Interval 1.17 to 6.96	5.22 units on a scale Interval 2.35 to 8.09	4.01 units on a scale Interval 1.03 to 6.99
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 5	4.36 units on a scale Interval 1.44 to 7.27	5.16 units on a scale Interval 2.26 to 8.06	4.09 units on a scale Interval 1.09 to 7.08
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 6	3.46 units on a scale Interval 0.53 to 6.39	3.8 units on a scale Interval 0.88 to 6.73	3.37 units on a scale Interval 0.35 to 6.39
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 7	3.16 units on a scale Interval 0.2 to 6.12	3.66 units on a scale Interval 0.71 to 6.61	3.42 units on a scale Interval 0.38 to 6.45
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 8	2.61 units on a scale Interval -0.37 to 5.59	2.71 units on a scale Interval -0.27 to 5.68	1.67 units on a scale Interval -1.39 to 4.73
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 9	2.2 units on a scale Interval -0.87 to 5.27	2.67 units on a scale Interval -0.35 to 5.68	1.89 units on a scale Interval -1.22 to 5.01
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 10	2.08 units on a scale Interval -1.05 to 5.21	2.09 units on a scale Interval -0.99 to 5.18	1.84 units on a scale Interval -1.32 to 5.0
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 11	0.15 units on a scale Interval -3.18 to 3.47	3.35 units on a scale Interval 0.1 to 6.6	2.68 units on a scale Interval -0.67 to 6.02
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 12	0.52 units on a scale Interval -2.94 to 3.97	3.95 units on a scale Interval 0.61 to 7.29	0.63 units on a scale Interval -2.78 to 4.05
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 13	1.79 units on a scale Interval -1.94 to 5.53	2.48 units on a scale Interval -0.95 to 5.91	0.55 units on a scale Interval -3.0 to 4.09
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 14	-1.78 units on a scale Interval -5.56 to 2.0	2.2 units on a scale Interval -1.29 to 5.69	-0.42 units on a scale Interval -4.06 to 3.21
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 15	-3.49 units on a scale Interval -7.5 to 0.51	1.74 units on a scale Interval -1.82 to 5.3	1.22 units on a scale Interval -2.51 to 4.95
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Cycle 16	-3.83 units on a scale Interval -7.89 to 0.23	1.62 units on a scale Interval -2.11 to 5.35	0.5 units on a scale Interval -3.3 to 4.3
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Follow-up 1	-1.08 units on a scale Interval -4.15 to 1.99	-1.45 units on a scale Interval -4.48 to 1.59	-1.82 units on a scale Interval -4.97 to 1.32
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Follow-up 2	-0.02 units on a scale Interval -3.16 to 3.13	-1.98 units on a scale Interval -5.17 to 1.21	-1.78 units on a scale Interval -5.04 to 1.47
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Follow-up 3	-0.55 units on a scale Interval -3.83 to 2.74	-2.16 units on a scale Interval -5.47 to 1.14	-2.68 units on a scale Interval -6.08 to 0.72
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Follow-up 4	-1.19 units on a scale Interval -4.61 to 2.23	-3.64 units on a scale Interval -7.18 to -0.1	-1.7 units on a scale Interval -5.25 to 1.84
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Follow-up 5	-2.05 units on a scale Interval -5.61 to 1.51	-6.73 units on a scale Interval -10.39 to -3.06	-0.6 units on a scale Interval -4.18 to 2.99
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) Change at Follow-up 6	-1.17 units on a scale Interval -4.92 to 2.58	-5.36 units on a scale Interval -9.32 to -1.4	-4.05 units on a scale Interval -7.87 to -0.23

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 (each cycle 21-day); post-treatment follow up 1, 2, 3, 4, 5, 6 (each up to 12 weeks)

FACT-P was a 39-item participant rated questionnaire that measures the concerns of participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). Physical well being, functional well being, and prostate-specific concerns sub-scales of the FACT-P questionnaire were combined to calculate TOI. Total TOI score ranges from 0 to 104, with higher scores representing a better quality of life with fewer symptoms.

Outcome measures

Outcome measures
Measure	Docetaxel 75 mg/m^2 n=376 Participants Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=371 Participants Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21 -day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=361 Participants Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 1	3.31 units on a scale Interval 1.05 to 5.58	6.09 units on a scale Interval 3.83 to 8.35	5.76 units on a scale Interval 3.43 to 8.09
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 2	4.37 units on a scale Interval 2.1 to 6.64	5.96 units on a scale Interval 3.7 to 8.21	4.26 units on a scale Interval 1.92 to 6.59
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 3	4.31 units on a scale Interval 2.04 to 6.58	5.28 units on a scale Interval 3.02 to 7.53	3.65 units on a scale Interval 1.31 to 5.99
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 4	3.39 units on a scale Interval 1.11 to 5.67	4.1 units on a scale Interval 1.83 to 6.36	3.2 units on a scale Interval 0.85 to 5.55
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 5	3.41 units on a scale Interval 1.11 to 5.7	4.05 units on a scale Interval 1.76 to 6.34	3.1 units on a scale Interval 0.74 to 5.46
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 6	2.76 units on a scale Interval 0.45 to 5.07	3.15 units on a scale Interval 0.85 to 5.46	2.88 units on a scale Interval 0.5 to 5.26
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 7	2.29 units on a scale Interval -0.05 to 4.62	3.14 units on a scale Interval 0.81 to 5.47	2.94 units on a scale Interval 0.54 to 5.34
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 8	1.67 units on a scale Interval -0.69 to 4.02	2.26 units on a scale Interval -0.09 to 4.61	1.49 units on a scale Interval -0.92 to 3.91
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 9	1.75 units on a scale Interval -0.67 to 4.18	2.15 units on a scale Interval -0.24 to 4.53	1.73 units on a scale Interval -0.73 to 4.19
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 10	1.52 units on a scale Interval -0.96 to 4.0	1.56 units on a scale Interval -0.88 to 3.99	1.62 units on a scale Interval -0.89 to 4.12
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 11	0.35 units on a scale Interval -2.29 to 3.0	2.72 units on a scale Interval 0.15 to 5.3	2.19 units on a scale Interval -0.46 to 4.84
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 12	1.04 units on a scale Interval -1.7 to 3.79	3.08 units on a scale Interval 0.43 to 5.73	0.75 units on a scale Interval -1.95 to 3.46
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 13	2.13 units on a scale Interval -0.85 to 5.11	1.78 units on a scale Interval -0.94 to 4.5	0.82 units on a scale Interval -1.98 to 3.62
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 14	-0.13 units on a scale Interval -3.15 to 2.89	1.59 units on a scale Interval -1.18 to 4.36	-0.07 units on a scale Interval -2.95 to 2.81
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 15	-2.1 units on a scale Interval -5.29 to 1.09	1.29 units on a scale Interval -1.53 to 4.11	1.49 units on a scale Interval -1.47 to 4.45
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Cycle 16	-2.26 units on a scale Interval -5.49 to 0.97	1.23 units on a scale Interval -1.73 to 4.19	1.44 units on a scale Interval -1.59 to 4.47
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Follow-up 1	-0.96 units on a scale Interval -3.38 to 1.47	-1.26 units on a scale Interval -3.66 to 1.14	-1.62 units on a scale Interval -4.11 to 0.86
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Follow-up 2	-0.07 units on a scale Interval -2.56 to 2.42	-1.12 units on a scale Interval -3.65 to 1.41	-1.05 units on a scale Interval -3.62 to 1.53
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Follow-up 3	-0.32 units on a scale Interval -2.92 to 2.28	-1.67 units on a scale Interval -4.29 to 0.96	-1.98 units on a scale Interval -4.68 to 0.72
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Follow-up 4	-0.91 units on a scale Interval -3.62 to 1.8	-2.54 units on a scale Interval -5.36 to 0.29	-1.03 units on a scale Interval -3.84 to 1.78
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Follow-up 5	-2.15 units on a scale Interval -4.99 to 0.69	-5.36 units on a scale Interval -8.27 to -2.44	-0.82 units on a scale Interval -3.67 to 2.02
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL Change at Follow-up 6	-1.77 units on a scale Interval -4.75 to 1.2	-5.32 units on a scale Interval -8.49 to -2.16	-2.76 units on a scale Interval -5.82 to 0.3

Adverse Events

Docetaxel 75 mg/m^2

Serious events: 126 serious events

Other events: 353 other events

Deaths: 0 deaths

Cabazitaxel 20 mg/m^2

Serious events: 127 serious events

Other events: 323 other events

Deaths: 0 deaths

Cabazitaxel 25 mg/m^2

Serious events: 188 serious events

Other events: 354 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Docetaxel 75 mg/m^2 n=387 participants at risk Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=369 participants at risk Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=391 participants at risk Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Infections and infestations Abscess intestinal	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Abscess jaw	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Abscess oral	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Anal abscess	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.26% 1/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Appendicitis	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Appendicitis perforated	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Bacteraemia	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Cellulitis	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Cholecystitis infective	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Clostridium difficile colitis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.51% 2/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Clostridium difficile infection	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Cystitis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.26% 1/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Device related infection	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.54% 2/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.26% 1/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Endocarditis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Erysipelas	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Gastroenteritis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.54% 2/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.77% 3/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Gastrointestinal infection	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Infection	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Lower respiratory tract infection	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.26% 1/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Lung abscess	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Lung infection	1.3% 5/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.77% 3/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Mastoiditis	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Neutropenic infection	3.1% 12/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.81% 3/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.4% 21/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Neutropenic sepsis	0.78% 3/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	1.0% 4/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Peritonitis	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Pneumonia	2.1% 8/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.81% 3/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	3.1% 12/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Post procedural cellulitis	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Rectal abscess	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.26% 1/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Respiratory tract infection	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Sepsis	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.81% 3/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.77% 3/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Septic shock	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.77% 3/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Skin infection	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Staphylococcal osteomyelitis	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Staphylococcal sepsis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Tracheobronchitis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Tuberculosis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.26% 1/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Upper respiratory tract infection	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.26% 1/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Urinary tract infection	0.52% 2/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	2.4% 9/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	2.0% 8/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Urosepsis	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.51% 2/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Wound infection	0.26% 1/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.00% 0/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.

Other adverse events
Measure	Docetaxel 75 mg/m^2 n=387 participants at risk Docetaxel (TXT) 75 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 20 mg/m^2 n=369 participants at risk Cabazitaxel 20 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.	Cabazitaxel 25 mg/m^2 n=391 participants at risk Cabazitaxel 25 mg/m\^2 IV infusion on Day 1 of each 21-day cycle in combination with Prednisone 10 mg orally, once daily until DP, unacceptable toxicity or participant's refusal.
Infections and infestations Nasopharyngitis	6.5% 25/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.1% 19/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	3.8% 15/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Infections and infestations Urinary tract infection	1.8% 7/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	9.5% 35/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	8.4% 33/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Blood and lymphatic system disorders Neutropenia	2.1% 8/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	3.0% 11/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.4% 25/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Metabolism and nutrition disorders Decreased appetite	17.1% 66/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	13.6% 50/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	18.9% 74/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Psychiatric disorders Insomnia	7.2% 28/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.5% 24/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.1% 20/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Nervous system disorders Dizziness	6.5% 25/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.3% 27/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	8.7% 34/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Nervous system disorders Dysgeusia	18.1% 70/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	11.1% 41/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	15.1% 59/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Nervous system disorders Headache	8.0% 31/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.7% 21/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.9% 27/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Nervous system disorders Paraesthesia	6.2% 24/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.8% 25/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	3.6% 14/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Nervous system disorders Peripheral sensory neuropathy	25.1% 97/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	11.7% 43/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	12.3% 48/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Eye disorders Lacrimation increased	9.6% 37/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	2.2% 8/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.77% 3/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Vascular disorders Hypertension	4.1% 16/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.4% 20/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	3.1% 12/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Cough	9.8% 38/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.0% 26/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	8.4% 33/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.3% 36/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	9.8% 36/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	8.2% 32/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.7% 22/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	2.7% 10/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	4.3% 17/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Gastrointestinal disorders Abdominal pain	3.6% 14/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	9.2% 34/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	8.4% 33/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Gastrointestinal disorders Constipation	17.8% 69/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	24.4% 90/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	19.9% 78/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Gastrointestinal disorders Diarrhoea	36.2% 140/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	32.5% 120/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	48.6% 190/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Gastrointestinal disorders Dyspepsia	3.4% 13/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.4% 20/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	3.8% 15/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Gastrointestinal disorders Nausea	22.2% 86/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	24.9% 92/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	32.0% 125/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Gastrointestinal disorders Stomatitis	13.7% 53/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	4.9% 18/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.6% 26/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Gastrointestinal disorders Vomiting	11.4% 44/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	11.9% 44/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	19.2% 75/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Skin and subcutaneous tissue disorders Alopecia	39.0% 151/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	8.9% 33/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	13.0% 51/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Skin and subcutaneous tissue disorders Nail disorder	9.0% 35/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.27% 1/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.77% 3/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Skin and subcutaneous tissue disorders Rash	5.9% 23/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	0.81% 3/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	1.3% 5/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Musculoskeletal and connective tissue disorders Arthralgia	8.0% 31/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	9.2% 34/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	11.0% 43/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Musculoskeletal and connective tissue disorders Back pain	13.4% 52/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	17.3% 64/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	14.1% 55/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Musculoskeletal and connective tissue disorders Bone pain	6.2% 24/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	8.4% 31/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.4% 29/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Musculoskeletal and connective tissue disorders Muscle spasms	3.9% 15/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.6% 28/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	3.3% 13/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Musculoskeletal and connective tissue disorders Myalgia	7.2% 28/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.0% 22/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.6% 22/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pain in extremity	9.8% 38/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.0% 26/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	4.9% 19/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Renal and urinary disorders Dysuria	2.3% 9/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.2% 23/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	5.4% 21/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Renal and urinary disorders Haematuria	3.4% 13/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	18.7% 69/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	23.3% 91/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
General disorders Asthenia	24.3% 94/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	22.8% 84/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	23.0% 90/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
General disorders Fatigue	28.4% 110/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	28.5% 105/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	32.2% 126/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
General disorders Oedema peripheral	20.2% 78/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	9.8% 36/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.7% 30/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
General disorders Pyrexia	9.3% 36/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	6.0% 22/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.2% 28/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Investigations Blood creatinine increased	3.6% 14/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.3% 27/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	4.1% 16/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Investigations Weight decreased	4.9% 19/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	4.6% 17/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	10.2% 40/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.
Injury, poisoning and procedural complications Incorrect dose administered	0.00% 0/387 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	1.6% 6/369 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.	7.7% 30/391 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (up to 83 months) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from first dose of study drug until 30 days after the last administration of study drug). Analysis was performed on safety population, which was randomized participants who received study drug and analyzed according to the treatment actually received.