Trial Outcomes & Findings for An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC) (NCT NCT04076059)

NCT ID: NCT04076059

Last Updated: 2026-02-06

Results Overview

Time to PSA progression was calculated as the time from the date of randomization to the first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 microgram/liter (μg/L) (2 nanogram/milliliter \[ng/mL\]) above the nadir (i.e., lowest PSA value observed post baseline or at baseline), which was confirmed by a second consecutive value at least 3 weeks later. Time to event analysis was performed using Kaplan-Meier estimates.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 180 participants
• Primary outcome timeframe: From the date of randomization to the first observation of PSA progression (up to 38 months)
• Results posted on: 2026-02-06

Participant Flow

Chinese men with metastatic hormone sensitive prostate cancer were enrolled in the study.

Participants who met all inclusion criteria and none of the exclusion criteria were enrolled in the study. Randomization was stratified by volume of disease (low versus high) and prior docetaxel therapy for prostate cancer (no prior docetaxel, prior docetaxel).

Participant milestones

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Enzalutamide Plus ADT (Open-Label Phase) Participants who received placebo in double-blind phase and remaind on study treatment until confirmed radiographic disease progression received enzalutamide and continued ADT in open-label phase. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Double Blind Phase STARTED	120	60	0
Double Blind Phase Ongoing Participants	82	18	0
Double Blind Phase Participants Who Received at Least One Dose of Study Drug	119	59	0
Double Blind Phase COMPLETED	0	0	0
Double Blind Phase NOT COMPLETED	120	60	0
Open Label Phase STARTED	0	0	23
Open Label Phase COMPLETED	0	0	0
Open Label Phase NOT COMPLETED	0	0	23

Reasons for withdrawal

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Enzalutamide Plus ADT (Open-Label Phase) Participants who received placebo in double-blind phase and remaind on study treatment until confirmed radiographic disease progression received enzalutamide and continued ADT in open-label phase. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Double Blind Phase Progressive disease	22	26	0
Double Blind Phase Withdrawal by Subject	4	11	0
Double Blind Phase Death	1	1	0
Double Blind Phase Lost to Follow-up	1	0	0
Double Blind Phase Adverse Event	5	1	0
Double Blind Phase Ongoing Participants	82	18	0
Double Blind Phase Miscellaneous	3	1	0
Double Blind Phase Protocol Deviation	1	1	0
Double Blind Phase Did not take study drug	1	1	0
Open Label Phase Progressive disease	0	0	7
Open Label Phase Withdrawal by Subject	0	0	3
Open Label Phase Death	0	0	2
Open Label Phase Ongoing Participants	0	0	11

Baseline Characteristics

An Efficacy and Safety Study of Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus ADT in Chinese Patients With Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

Baseline characteristics by cohort

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Total n=180 Participants Total of all reporting groups
Age, Continuous	68.8 Years STANDARD_DEVIATION 7.4 • n=192 Participants	68.7 Years STANDARD_DEVIATION 7.3 • n=170 Participants	68.8 Years STANDARD_DEVIATION 7.3 • n=185 Participants
Sex: Female, Male Female	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Sex: Female, Male Male	120 Participants n=192 Participants	60 Participants n=170 Participants	180 Participants n=185 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	120 Participants n=192 Participants	60 Participants n=170 Participants	180 Participants n=185 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Race (NIH/OMB) Asian	120 Participants n=192 Participants	60 Participants n=170 Participants	180 Participants n=185 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Race (NIH/OMB) Black or African American	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Race (NIH/OMB) White	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Race (NIH/OMB) More than one race	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=192 Participants	0 Participants n=170 Participants	0 Participants n=185 Participants
Prior Docetaxel Use (yes or no) Yes	14 Participants n=192 Participants	8 Participants n=170 Participants	22 Participants n=185 Participants
Prior Docetaxel Use (yes or no) No	106 Participants n=192 Participants	52 Participants n=170 Participants	158 Participants n=185 Participants
Volume of Disease (Low Vs High) Low	26 Participants n=192 Participants	14 Participants n=170 Participants	40 Participants n=185 Participants
Volume of Disease (Low Vs High) High	94 Participants n=192 Participants	46 Participants n=170 Participants	140 Participants n=185 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the first observation of PSA progression (up to 38 months)

Population: ITT Population

Time to PSA progression was calculated as the time from the date of randomization to the first observation of PSA progression. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 microgram/liter (μg/L) (2 nanogram/milliliter [ng/mL]) above the nadir (i.e., lowest PSA value observed post baseline or at baseline), which was confirmed by a second consecutive value at least 3 weeks later. Time to event analysis was performed using Kaplan-Meier estimates.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Time to Prostrate Specific Antigen (PSA) Progression	NA Months Not Reached. Data was not estimable due to low number of events	9.2 Months Interval 6.54 to 17.48

SECONDARY outcome

Timeframe: up to 38 months

Population: ITT Population

An rPFS event was defined as the time from randomization to the first objective evidence of radiographic disease progression assessed by investigator or death (defined as death from any cause within 24 weeks from study drug discontinuation), whichever occurred first. Radiographic disease progression was defined as progressive disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan. Time to event analysis was performed using Kaplan-Meier estimates.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Radiographic Progression-Free Survival (rPFS)	NA Months Interval 28.25 to Not Reached. Median and upper CI was not estimable due to low number of events	19.4 Months Interval 13.63 to Not Reached. Upper CI was not estimable due to low number of events

SECONDARY outcome

Timeframe: Up to 38 months

Population: ITT Population

Time to first SSE was defined as the time from randomization to the occurrence of the first SSE. SSE was defined as radiation or surgery to bone, clinically apparent pathological bone fracture or spinal cord compression. Time to event analysis was performed using Kaplan-Meier estimates.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Time to First Symptomatic Skeletal Event (SSE)	NA Months Not Reached. Data was not reached due to low number of events	NA Months Not Reached. Data was not reached due to low number of events

SECONDARY outcome

Timeframe: Up to 38 months

Population: ITT Population

Castration resistance was defined as occurrence of radiographic disease progression, PSA progression or SSE with castrate levels of testosterone (< 50 ng/dL). Time to castration resistance was defined as the time from randomization to the first castration resistant event (radiographic disease progression, PSA progression or SSE), whichever occurred first. PSA progression was defined as a ≥ 25% increase and an absolute increase of ≥ 2 μg/L (2 ng/mL) above the nadir (i.e., lowest PSA value observed post baseline or at baseline), which was confirmed by a second consecutive value at least 3 weeks later. Radiographic disease progression was defined as progressive disease by RECIST version 1.1 for soft tissue disease or by appearance of 2 or more new lesions on bone scan. SSE was defined as radiation or surgery to bone, clinically apparent pathological bone fracture or spinal cord compression. Time to event analysis was performed using Kaplan-Meier estimates.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Time to Castration Resistance	NA Months Interval 31.18 to Median and upper CI was not estimable due to low number of events	8.3 Months Interval 6.41 to 14.69

SECONDARY outcome

Timeframe: Up to 38 months

Population: ITT Population

The PSA response rate ≥50% is defined as the percentage of participants in the analysis population with maximal PSA declines of at least 50% at any time and at each visit for participants with detectable PSA at baseline and at least 1 post-baseline assessment.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Percentage of Participants With PSA Response (≥ 50%)	93.3 Percentage of participants Interval 87.3 to 97.1	80.0 Percentage of participants Interval 67.7 to 89.2

SECONDARY outcome

Timeframe: Up to 38 months

Population: ITT Population

The PSA response rate ≥90% is defined as the percentage of participants in the analysis population with maximal PSA declines of at least 90% at any time and at each visit for participants with detectable PSA at baseline and at least 1 post-baseline assessment.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Percentage of Participants With PSA Response (≥ 90%)	86.7 Percentage of participants Interval 79.3 to 92.2	55.0 Percentage of participants Interval 41.6 to 67.9

SECONDARY outcome

Timeframe: Up to 38 months

Population: ITT Population

Time to initiate of a new antineoplastic therapy (including cytotoxic and hormone therapies) was defined as the time interval from randomization to the date of the first dose administration of the first antineoplastic therapy. Time to event analysis was performed using Kaplan-Meier estimates.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=120 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=60 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Time to Initiation of New Antineoplastic Therapy	NA Months Not Reached. Data was not reached due to low number of events	31.1 Months Not Reached. Data was not reached due to low number of events

SECONDARY outcome

Timeframe: Up to 38 months

Population: ITT Population with detectable PSA at baseline

The PSA undetectable rate was defined as the percentage of participants with detectable (≥ 0.2 ng/mL) PSA at baseline, which became undetectable (< 0.2 ng/mL) during study treatment. Only participants with detectable PSA at baseline was included in the analysis.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=114 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=57 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Percentage of Participants With Undetectable PSA (< 0.2 ng/mL)	76.3 Percentage of participants Interval 67.4 to 83.8	22.8 Percentage of participants Interval 12.7 to 35.8

SECONDARY outcome

Timeframe: Up to 38 months

Population: ITT Population with measurable soft tissue disease at baseline

The ORR was defined as the percentage of participants with measurable disease at baseline who achieved a complete or partial response (CR or PR) in their soft tissue disease using the RECIST version 1.1 criteria, CR was defined as complete disappearance of all target lesions and non-target disease. No new lesions. PR was defined as >=30% decrease on study under baseline of the sum of longest diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions.

Outcome measures

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=47 Participants Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=22 Participants Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Objective Response Rate (ORR)	76.6 Percentage of participants Interval 62.0 to 87.7	81.8 Percentage of participants Interval 59.7 to 94.8

Adverse Events

Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase)

Serious events: 42 serious events

Other events: 115 other events

Deaths: 21 deaths

Placebo Plus ADT (Double Blind Phase)

Serious events: 12 serious events

Other events: 54 other events

Deaths: 12 deaths

Enzalutamide Plus ADT (Open-Label Phase)

Serious events: 5 serious events

Other events: 16 other events

Deaths: 8 deaths

Serious adverse events

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=119 participants at risk Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=59 participants at risk Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Enzalutamide Plus ADT (Open-Label Phase) n=23 participants at risk Participants who received placebo in double-blind phase and remaind on study treatment until confirmed radiographic disease progression received enzalutamide and continued ADT in open-label phase. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Blood and lymphatic system disorders Anaemia	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Cardiac disorders Acute myocardial infarction	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Cardiac disorders Arteriosclerosis coronary artery	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Cardiac disorders Atrial fibrillation	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Cardiac disorders Atrial flutter	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Cardiac disorders Atrioventricular block complete	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Ear and labyrinth disorders Hypoacusis	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Ear and labyrinth disorders Vertigo positional	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Endocrine disorders Goitre	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Eye disorders Diabetic retinopathy	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Eye disorders Optic ischaemic neuropathy	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Mesenteric artery embolism	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
General disorders Pyrexia	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Hepatobiliary disorders Acute hepatic failure	0.84% 1/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Hepatobiliary disorders Cholecystitis	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Hepatobiliary disorders Hepatic function abnormal	3.4% 4/119 • Number of events 9 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Hepatobiliary disorders Liver injury	1.7% 2/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Infection	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Sepsis	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Urinary tract infection	0.84% 1/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Urinary tract infection bacterial	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Injury, poisoning and procedural complications Ankle fracture	1.7% 2/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Injury, poisoning and procedural complications Clavicle fracture	1.7% 2/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Injury, poisoning and procedural complications Foot fracture	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Injury, poisoning and procedural complications Rib fracture	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Injury, poisoning and procedural complications Spinal compression fracture	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Injury, poisoning and procedural complications Tibia fracture	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Alanine aminotransferase increased	1.7% 2/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hyperglycaemia	0.84% 1/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Bone pain	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	1.7% 2/119 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenoma	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Cerebral infarction	6.7% 8/119 • Number of events 10 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Hypoaesthesia	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Lacunar infarction	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Paraplegia	0.00% 0/119 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Syncope	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Psychiatric disorders Insomnia	0.84% 1/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Acute kidney injury	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Calculus bladder	1.7% 2/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Haematuria	1.7% 2/119 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Ureterolithiasis	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Urinary retention	1.7% 2/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Urinary tract obstruction	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Reproductive system and breast disorders Benign prostatic hyperplasia	1.7% 2/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Reproductive system and breast disorders Scrotal oedema	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Vascular disorders Aortic thrombosis	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Vascular disorders Hypertension	3.4% 4/119 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Vascular disorders Penetrating aortic ulcer	0.84% 1/119 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).

Other adverse events

Measure	Enzalutamide Plus Androgen Deprivation Therapy (ADT) (Double Blind Phase) n=119 participants at risk Participants received enzalutamide 160 mg capsules, orally once daily if tolerable, and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Placebo Plus ADT (Double Blind Phase) n=59 participants at risk Participants received enzalutamide-matching placebo capsules, orally once daily and continued ADT until radiographic disease progression was documented or until they started another investigational agent or new therapy for treatment of prostate cancer. Participants were to remain on study treatment until confirmed radiographic disease progression. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.	Enzalutamide Plus ADT (Open-Label Phase) n=23 participants at risk Participants who received placebo in double-blind phase and remaind on study treatment until confirmed radiographic disease progression received enzalutamide and continued ADT in open-label phase. ADT (either bilateral orchiectomy or LHRH agonist/antagonist) was maintained during study treatment.
Blood and lymphatic system disorders Anaemia	34.5% 41/119 • Number of events 106 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	39.0% 23/59 • Number of events 45 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	26.1% 6/23 • Number of events 13 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Blood and lymphatic system disorders Leukocytosis	0.84% 1/119 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Abdominal distension	8.4% 10/119 • Number of events 11 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Constipation	7.6% 9/119 • Number of events 10 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Diarrhoea	4.2% 5/119 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Nausea	4.2% 5/119 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Toothache	7.6% 9/119 • Number of events 9 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Gastrointestinal disorders Vomiting	5.0% 6/119 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
General disorders Asthenia	5.9% 7/119 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
General disorders Chest discomfort	2.5% 3/119 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
General disorders Fatigue	15.1% 18/119 • Number of events 21 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	10.2% 6/59 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
General disorders Malaise	9.2% 11/119 • Number of events 11 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
General disorders Oedema peripheral	11.8% 14/119 • Number of events 20 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	6.8% 4/59 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
General disorders Pyrexia	3.4% 4/119 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Hepatobiliary disorders Hepatic function abnormal	2.5% 3/119 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Mastoiditis	8.4% 10/119 • Number of events 11 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Sinusitis	6.7% 8/119 • Number of events 8 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Upper respiratory tract infection	6.7% 8/119 • Number of events 8 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Infections and infestations Urinary tract infection	9.2% 11/119 • Number of events 15 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Injury, poisoning and procedural complications Rib fracture	5.0% 6/119 • Number of events 8 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Alanine aminotransferase increased	18.5% 22/119 • Number of events 52 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	25.4% 15/59 • Number of events 32 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	13.0% 3/23 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Aspartate aminotransferase increased	19.3% 23/119 • Number of events 32 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	22.0% 13/59 • Number of events 25 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	13.0% 3/23 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Blood alkaline phosphatase increased	7.6% 9/119 • Number of events 28 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	18.6% 11/59 • Number of events 26 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	17.4% 4/23 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Blood bilirubin increased	10.9% 13/119 • Number of events 33 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	15.3% 9/59 • Number of events 16 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Blood creatinine increased	5.9% 7/119 • Number of events 18 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Gamma-glutamyltransferase increased	5.0% 6/119 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	6.8% 4/59 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Neutrophil count decreased	6.7% 8/119 • Number of events 60 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Platelet count decreased	5.9% 7/119 • Number of events 25 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 8 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Weight decreased	9.2% 11/119 • Number of events 20 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations Weight increased	42.0% 50/119 • Number of events 208 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	32.2% 19/59 • Number of events 46 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	17.4% 4/23 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Investigations White blood cell count decreased	6.7% 8/119 • Number of events 58 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 13 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Decreased appetite	16.0% 19/119 • Number of events 22 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 8 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	17.4% 4/23 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hypercalcaemia	10.1% 12/119 • Number of events 33 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hypercholesterolaemia	11.8% 14/119 • Number of events 36 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	13.6% 8/59 • Number of events 18 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hyperglycaemia	26.1% 31/119 • Number of events 89 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	20.3% 12/59 • Number of events 32 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	17.4% 4/23 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hyperkalaemia	3.4% 4/119 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	6.8% 4/59 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hyperlipidaemia	10.1% 12/119 • Number of events 28 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	6.8% 4/59 • Number of events 10 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hypermagnesaemia	2.5% 3/119 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hyperphosphataemia	8.4% 10/119 • Number of events 32 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	6.8% 4/59 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hypertriglyceridaemia	27.7% 33/119 • Number of events 147 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	20.3% 12/59 • Number of events 42 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	13.0% 3/23 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hyperuricaemia	12.6% 15/119 • Number of events 41 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	11.9% 7/59 • Number of events 16 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hypoalbuminaemia	6.7% 8/119 • Number of events 13 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hypochloraemia	6.7% 8/119 • Number of events 24 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	10.2% 6/59 • Number of events 8 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hypokalaemia	10.9% 13/119 • Number of events 28 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	15.3% 9/59 • Number of events 21 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Metabolism and nutrition disorders Hyponatraemia	4.2% 5/119 • Number of events 11 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	10.2% 6/59 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Arthralgia	15.1% 18/119 • Number of events 23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	15.3% 9/59 • Number of events 10 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Arthritis	5.9% 7/119 • Number of events 10 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Back pain	10.1% 12/119 • Number of events 25 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	13.0% 3/23 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Bone hypertrophy	8.4% 10/119 • Number of events 40 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Bone pain	10.9% 13/119 • Number of events 18 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	20.3% 12/59 • Number of events 16 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Muscular weakness	8.4% 10/119 • Number of events 10 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	9.2% 11/119 • Number of events 12 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Osteitis	11.8% 14/119 • Number of events 29 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	13.0% 3/23 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Osteoarthritis	7.6% 9/119 • Number of events 11 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/59 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Musculoskeletal and connective tissue disorders Pain in extremity	10.1% 12/119 • Number of events 17 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.5% 5/59 • Number of events 8 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Dizziness	12.6% 15/119 • Number of events 19 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	13.6% 8/59 • Number of events 11 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Headache	7.6% 9/119 • Number of events 9 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Nervous system disorders Hypoaesthesia	8.4% 10/119 • Number of events 13 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Psychiatric disorders Insomnia	12.6% 15/119 • Number of events 18 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Dysuria	8.4% 10/119 • Number of events 16 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	3.4% 2/59 • Number of events 5 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Haematuria	7.6% 9/119 • Number of events 23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Micturition urgency	7.6% 9/119 • Number of events 10 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Pollakiuria	9.2% 11/119 • Number of events 14 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	10.2% 6/59 • Number of events 7 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Renal and urinary disorders Urinary retention	4.2% 5/119 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	6.8% 4/59 • Number of events 4 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Skin and subcutaneous tissue disorders Night sweats	4.2% 5/119 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	5.1% 3/59 • Number of events 3 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	4.3% 1/23 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Skin and subcutaneous tissue disorders Pruritus	5.0% 6/119 • Number of events 6 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	1.7% 1/59 • Number of events 1 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	0.00% 0/23 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Vascular disorders Hot flush	19.3% 23/119 • Number of events 28 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	15.3% 9/59 • Number of events 9 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).
Vascular disorders Hypertension	25.2% 30/119 • Number of events 68 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	32.2% 19/59 • Number of events 41 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).	8.7% 2/23 • Number of events 2 • From the first dose up to 38 months The safety (SAF) population included all randomized participants who received at least 1 dose of study drug. Data reported for deaths are the number of participants who died regardless of time (could be beyond treatment emergent adverse event time frame).

Additional Information

Clinical Transparency

Astellas Pharma China, Inc

Phone: +86-(0)10-85216666

Email: astellas.resultsdisclosure@astellas.com

Results disclosure agreements

• Principal investigator is a sponsor employee Principal Investigators (PI) are NOT employed by the organization sponsoring the study. There IS an agreement between PI's and the Sponsor that restricts the PI's rights to discuss or publish trial results after the trial is completed. Institute and/or PI may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
• Publication restrictions are in place

Restriction type: OTHER