Trial Outcomes & Findings for Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer (NCT NCT01951586)

NCT ID: NCT01951586

Last Updated: 2021-10-25

Results Overview

Overall survival was calculated as the time from the date of randomization to the date of death from any cause. Participants last known to be alive were censored at the last contact date.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 226 participants
• Primary outcome timeframe: From randomization until the end of study; median time on study was 9.64 months.
• Results posted on: 2021-10-25

Participant Flow

This study was conducted at 57 centers in 10 countries including the United Kingdom, Netherlands, France, Italy, Germany, Czech Republic, United States, Canada, Australia and Greece. Participants were enrolled from 31 December 2013 to 21 May 2015.

Participants were randomized in a 2:1 ratio to receive denosumab or placebo. Randomization was stratified based on the presence of bone metastasis (yes or no), histology (squamous versus non-squamous), and geographic region (North America, Western Europe/Australia, and rest of world [ROW]).

Participant milestones

Measure	Placebo Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Overall Study STARTED	78	148
Overall Study Received Study Drug	76	145
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	78	148

Reasons for withdrawal

Measure	Placebo Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Overall Study Death	61	120
Overall Study Withdrawal by Subject	8	17
Overall Study Lost to Follow-up	0	1
Overall Study Sponsor Decision	9	10

Baseline Characteristics

Denosumab in Combination With Chemotherapy as First-line Treatment of Metastatic Non-small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Placebo n=78 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=148 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.	Total n=226 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 10.1 • n=5 Participants	63.8 years STANDARD_DEVIATION 9.7 • n=7 Participants	63.8 years STANDARD_DEVIATION 9.8 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	54 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	94 Participants n=7 Participants	152 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	73 Participants n=5 Participants	133 Participants n=7 Participants	206 Participants n=5 Participants
Race/Ethnicity, Customized Others	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Presence of Bone Metastasis Yes	35 Participants n=5 Participants	65 Participants n=7 Participants	100 Participants n=5 Participants
Presence of Bone Metastasis No	43 Participants n=5 Participants	83 Participants n=7 Participants	126 Participants n=5 Participants
Histology Squamous	18 Participants n=5 Participants	35 Participants n=7 Participants	53 Participants n=5 Participants
Histology Non-squamous	60 Participants n=5 Participants	113 Participants n=7 Participants	173 Participants n=5 Participants
Geographic region North America/Australia	30 Participants n=5 Participants	63 Participants n=7 Participants	93 Participants n=5 Participants
Geographic region Western Europe	35 Participants n=5 Participants	67 Participants n=7 Participants	102 Participants n=5 Participants
Geographic region Rest of World	13 Participants n=5 Participants	18 Participants n=7 Participants	31 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active)	33 Participants n=5 Participants	69 Participants n=7 Participants	102 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restrictive but ambulatory)	45 Participants n=5 Participants	79 Participants n=7 Participants	124 Participants n=5 Participants
Time from Initial Diagnosis of NSCLC to Randomization	2.46 months STANDARD_DEVIATION 5.28 • n=5 Participants	6.32 months STANDARD_DEVIATION 16.96 • n=7 Participants	4.99 months STANDARD_DEVIATION 14.17 • n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the end of study; median time on study was 9.64 months.

Population: All randomized participants

Overall survival was calculated as the time from the date of randomization to the date of death from any cause. Participants last known to be alive were censored at the last contact date.

Outcome measures

Measure	Placebo n=78 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=148 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Overall Survival (OS)	10.9 months Interval 9.26 to 15.54	10.7 months Interval 8.54 to 12.35

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Population: All randomized participants who had evaluable pre-treatment tumor RANK expression.

To assess whether the treatment effect on overall survival was correlated with receptor activator of nuclear factor (NF)-κB (RANK) protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.

The correlation between RANK expression level and OS was evaluated using a Cox proportional hazard models that included RANK expression level stratified by the randomization stratification factors in the corresponding treatment group.

Outcome measures

Measure	Placebo n=64 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=123 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Correlation of Tumor Tissue RANK Expression With Overall Survival Cytoplasm all intensity	0.84 hazard ratio Interval 0.65 to 1.09	1.00 hazard ratio Interval 0.85 to 1.17
Correlation of Tumor Tissue RANK Expression With Overall Survival Membrane all intensity	0.72 hazard ratio Interval 0.51 to 1.01	0.92 hazard ratio Interval 0.74 to 1.14
Correlation of Tumor Tissue RANK Expression With Overall Survival Total all intensity	0.80 hazard ratio Interval 0.62 to 1.03	1.00 hazard ratio Interval 0.85 to 1.17
Correlation of Tumor Tissue RANK Expression With Overall Survival Cytoplasm H-score	0.83 hazard ratio Interval 0.65 to 1.07	1.00 hazard ratio Interval 0.86 to 1.16
Correlation of Tumor Tissue RANK Expression With Overall Survival Membrane H-score	0.72 hazard ratio Interval 0.52 to 1.0	0.93 hazard ratio Interval 0.77 to 1.13
Correlation of Tumor Tissue RANK Expression With Overall Survival Total H-score	0.80 hazard ratio Interval 0.62 to 1.02	1.00 hazard ratio Interval 0.86 to 1.16

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Population: All randomized participants who had evaluable pre-treatment tumor RANKL expression.

To assess whether the treatment effect on overall survival was correlated with RANK ligand (RANKL) protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.

The correlation between RANKL expression level and OS was evaluated using a Cox proportional hazard models that included RANKL expression level stratified by the randomization stratification factors in the corresponding treatment group.

Outcome measures

Measure	Placebo n=65 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=121 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival Cytoplasm all intensity	0.77 hazard ratio Interval 0.63 to 0.95	0.93 hazard ratio Interval 0.82 to 1.05
Correlation of Tumor Tissue RANK Ligand Expression With Overall Survival Cytoplasm H-score	0.79 hazard ratio Interval 0.66 to 0.95	0.93 hazard ratio Interval 0.84 to 1.04

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Population: Randomized participants with at least one baseline measurable lesion per modified RECIST 1.1.

Objective response rate was defined as the percentage of participants with a complete response (CR) or partial response (PR) based on modified RECIST 1.1 achieved over the study duration.

CR: Disappearance of all target and non target lesions, normalization of tumor marker levels and no new lesions.

PR: At least a 30% decrease in the size of target lesions with no progression of non-target lesions and no new lesions, or, disappearance of target lesions with persistence of one or more non-target lesions and/or maintenance of tumor marker levels above normal limits and no new lesions.

Participants who underwent surgical resection while on study were not evaluated for response after the surgery. Participants who did not meet the criteria for an objective response by the analysis cutoff date were considered non-responders.

Outcome measures

Measure	Placebo n=76 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=144 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Objective Response Rate	43.4 percentage of participants	36.8 percentage of participants

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Population: All randomized participants with at least one baseline measurable lesion per modified RECIST 1.1 who had evaluable pre-treatment tumor RANK expression.

To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANK protein expression in tumor cells, RANK expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm, membrane, and total was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.

The correlation between RANK expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANK expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported.

Outcome measures

Measure	Placebo n=63 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=119 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Correlation of Tumor Tissue RANK Expression With Objective Response Rate Cytoplasm all intensity	1.00 odds ratio Interval 0.67 to 1.5	0.88 odds ratio Interval 0.68 to 1.13
Correlation of Tumor Tissue RANK Expression With Objective Response Rate Membrane all intensity	1.18 odds ratio Interval 0.74 to 1.89	0.82 odds ratio Interval 0.57 to 1.17
Correlation of Tumor Tissue RANK Expression With Objective Response Rate Total all intensity	1.16 odds ratio Interval 0.78 to 1.71	0.88 odds ratio Interval 0.68 to 1.13
Correlation of Tumor Tissue RANK Expression With Objective Response Rate Cytoplasm H-score	1.00 odds ratio Interval 0.69 to 1.47	0.87 odds ratio Interval 0.68 to 1.11
Correlation of Tumor Tissue RANK Expression With Objective Response Rate Membrane H-score	1.14 odds ratio Interval 0.74 to 1.76	0.82 odds ratio Interval 0.59 to 1.14
Correlation of Tumor Tissue RANK Expression With Objective Response Rate Total H-score	1.14 odds ratio Interval 0.79 to 1.65	0.87 odds ratio Interval 0.69 to 1.11

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Population: All randomized participants with at least one baseline measurable lesion per modified RECIST 1.1 who had evaluable pre-treatment tumor RANKL expression.

To assess whether the treatment effect on objective response rate (ORR) based on RECIST 1.1 was correlated with RANKL protein expression in tumor cells, RANKL expression in archival tumor samples was measured using immunohistochemistry. The intensity of stain in the cytoplasm was categorized as 0 (negative), 1+ (weak), 2+ (moderate) or 3+ (strong); All intensity is the sum of levels +1, +2 and +3. In addition, an H-score was calculated using the following formula: H-score=(percentage of cells of weak×1)+(percentage of cells of moderate×2)+(percentage of cells of strong×3). The maximum H-score was 300, corresponding to 100% of cells with strong intensity.

The correlation between RANKL expression level and ORR was evaluated within each treatment group using a logistical regression model that included RANKL expression value as an independent variable and stratified by the randomization stratification factors. The odds ratio and 95% confidence interval are reported.

Outcome measures

Measure	Placebo n=64 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=117 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Correlation of Tumor Tissue RANKL Expression With Objective Response Rate Cytoplasm all intensity	1.27 odds ratio Interval 0.88 to 1.83	1.10 odds ratio Interval 0.9 to 1.35
Correlation of Tumor Tissue RANKL Expression With Objective Response Rate Cytoplasm H-score	1.25 odds ratio Interval 0.91 to 1.72	1.09 odds ratio Interval 0.91 to 1.3

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Population: Randomized participants with at least one baseline measurable lesion per modified RECIST 1.1.

Clinical benefit rate was defined as the percentage of participants with an objective response (CR or PR) or stable disease (SD) or better for at least 16 weeks achieved over the study duration. If a participant underwent surgical resection while on study, the participant was not evaluated for response after the surgery. Participants who did not meet the criteria for clinical benefit by the analysis cutoff date were considered as non-responders.

Outcome measures

Measure	Placebo n=76 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=144 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Clinical Benefit Rate	53.9 percentage of participants	47.9 percentage of participants

SECONDARY outcome

Timeframe: From randomization until the data cut-off date of 29 July 2016; median time on study was 9.64 months.

Population: All randomized participants

Progression-free survival was defined as the time from randomization to the first observed disease progression per modified RECIST 1.1 criteria or death from any cause. Participants last known to be alive who did not experience disease progression were censored at their last imaging assessment date, last contact date if they were in the survival follow up phase, end of the study date, or the primary analysis cut-off date, whichever was first. If a participant underwent surgical resection while on study, the participant was censored at the last evaluable imaging assessment prior to the surgery.

Outcome measures

Measure	Placebo n=78 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=148 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Progression-free Survival (PFS)	5.7 months Interval 4.37 to 7.16	5.2 months Interval 4.24 to 5.78

SECONDARY outcome

Timeframe: Prior to dosing at day 8 and weeks 3, 6, 9, 12, 15, 18, 21 and 24.

Population: Randomized participants who received denosumab every 3 weeks with at least one valid denosumab concentration measurement.

Serum samples were analyzed for denosumab using enzyme-linked immunosorbent assay (ELISA) following a validated procedure. The lower limit of quantification for the assay was 20 ng/mL.

Outcome measures

Measure	Placebo n=104 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 2 - Day 8	8590 ng/mL Standard Deviation 4080	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 3 - Week 3	12200 ng/mL Standard Deviation 5710	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 4 - Week 6	19700 ng/mL Standard Deviation 7350	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 5 - Week 9	19600 ng/mL Standard Deviation 8270	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 6 - Week 12	22800 ng/mL Standard Deviation 10400	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 7 - Week 15	24300 ng/mL Standard Deviation 11500	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 8 - Week 18	22700 ng/mL Standard Deviation 10600	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 9 - Week 21	22100 ng/mL Standard Deviation 11200	—
Serum Denosumab Trough Levels in Participants Who Received Q3W Dosing Dose 10 - Week 24	23300 ng/mL Standard Deviation 12700	—

SECONDARY outcome

Timeframe: Prior to dosing at day 8 and weeks 4, 8, 12, 16, 20 and 24

Population: Randomized participants who received denosumab every 4 weeks with at least one valid denosumab concentration measurement.

Serum samples were analyzed for denosumab using enzyme-linked immunosorbent assay (ELISA) following a validated procedure. The lower limit of quantification for the assay was 20 ng/mL.

Outcome measures

Measure	Placebo n=8 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing Dose 2 - Day 8	8990 ng/mL Standard Deviation 2470	—
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing Dose 3 - Week 4	10900 ng/mL Standard Deviation 3170	—
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing Dose 4 - Week 8	15700 ng/mL Standard Deviation 6710	—
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing Dose 5 - Week 12	14500 ng/mL Standard Deviation 4940	—
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing Dose 6 - Week 16	13000 ng/mL Standard Deviation 4380	—
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing Dose 7 - Week 20	15400 ng/mL Standard Deviation 5620	—
Serum Denosumab Trough Levels in Participants Who Received Q4W Dosing Dose 8 - Week 24	15900 ng/mL Standard Deviation 7810	—

SECONDARY outcome

Timeframe: From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively.

Population: All randomized participants who received at least one dose of study drug (denosumab or placebo)

An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment.

A serious adverse event is defined as an AE that meets at least 1 of the following criteria

• fatal
• life threatening
• requires in-patient hospitalization or prolongation of existing hospitalization
• results in persistent or significant disability/incapacity
• congenital anomaly/birth defect
• other medically important serious event Treatment-related AEs include only TEAEs for which the investigator indicated there was a reasonable possibility they may have been caused by study drug.

Fatal adverse events include only deaths reported on the Adverse Event Case Report Form.

Outcome measures

Measure	Placebo n=76 Participants Participants were randomized to receive placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=145 Participants Participants were randomized to receive 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Number of Participants With Treatment-emergent Adverse Events All adverse events (AEs)	76 participants	144 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related serious adverse events	0 participants	6 participants
Number of Participants With Treatment-emergent Adverse Events TRAEs leading to discontinuation of study drug	0 participants	7 participants
Number of Participants With Treatment-emergent Adverse Events Serious adverse events	68 participants	129 participants
Number of Participants With Treatment-emergent Adverse Events AEs leading to discontinuation of study drug	6 participants	20 participants
Number of Participants With Treatment-emergent Adverse Events Fatal adverse events	53 participants	113 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related adverse events (TRAEs)	24 participants	51 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related fatal adverse events	0 participants	0 participants

Adverse Events

Placebo

Serious events: 68 serious events

Other events: 71 other events

Deaths: 0 deaths

Denosumab

Serious events: 129 serious events

Other events: 139 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=76 participants at risk Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=145 participants at risk Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	3.9% 3/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone marrow	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Anaemia	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.4% 5/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Febrile neutropenia	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Neutropenia	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Thrombocytopenia	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Acute myocardial infarction	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Atrial fibrillation	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac failure congestive	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac tamponade	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardio-respiratory arrest	3.9% 3/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Coronary artery insufficiency	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Myocardial infarction	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Palpitations	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Tachycardia	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Congenital, familial and genetic disorders Hereditary angioedema	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal wall haematoma	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Intestinal obstruction	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Melaena	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Asthenia	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Chest pain	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Chills	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Condition aggravated	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Disease progression	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.4% 5/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders General physical health deterioration	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 7/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Infusion site extravasation	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Malaise	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema peripheral	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pain	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.3% 12/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Hepatobiliary disorders Hepatic failure	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Hepatobiliary disorders Hyperbilirubinaemia	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Immune system disorders Anaphylactic reaction	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Bronchitis	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Cellulitis	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Device related infection	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Fungal infection	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Gangrene	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Gastroenteritis shigella	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lower respiratory tract infection	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lung abscess	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lung infection	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Oral herpes	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pleural infection	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia	9.2% 7/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.7% 14/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Respiratory tract infection	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Sepsis	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Septic shock	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Staphylococcal bacteraemia	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Fracture	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Radiation oesophagitis	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Radius fracture	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations C-reactive protein increased	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations General physical condition abnormal	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Glomerular filtration rate decreased	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Nutritional condition abnormal	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Platelet count decreased	3.9% 3/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Cachexia	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperglycaemia	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Vertebral lesion	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma stage IV	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	3.9% 3/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 9/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.9% 10/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung squamous cell carcinoma metastatic	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangiosis carcinomatosa	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	11.8% 9/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.1% 19/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	9.2% 7/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.7% 14/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer stage IV	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.3% 12/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Altered state of consciousness	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Brain oedema	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Cerebrovascular accident	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Consciousness fluctuating	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Depressed level of consciousness	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Epilepsy	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Haemorrhage intracranial	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Ischaemic stroke	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Lethargy	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Loss of consciousness	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Seizure	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Stroke in evolution	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Transient ischaemic attack	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Product Issues Device issue	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Confusional state	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Delirium	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Mental status changes	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Suicide attempt	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Acute kidney injury	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Haematuria	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal haemorrhage	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.4% 5/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.0% 16/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Laryngeal mass	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Laryngeal obstruction	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Lung disorder	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Aortic thrombosis	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Circulatory collapse	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Deep vein thrombosis	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Embolism	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Embolism venous	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Jugular vein thrombosis	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Superior vena cava syndrome	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Thrombosis	0.00% 0/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Generalised tonic-clonic seizure	1.3% 1/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Measure	Placebo n=76 participants at risk Participants received placebo matching to denosumab by subcutaneous injection once every 4 weeks (Q4W) plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received placebo as often as once every 3 weeks (Q3W) while receiving Q3W chemotherapy. Participants with bone metastases also received 4 mg zoledronic acid administered as an IV infusion Q4W or Q3W.	Denosumab n=145 participants at risk Participants received 120 mg denosumab by subcutaneous injection once every 4 weeks plus one loading dose on study day 8 in addition to platinum-based standard chemotherapy. Participants may have received denosumab as often as Q3W while receiving Q3W chemotherapy. Participants with bone metastases also received placebo to zoledronic acid administered as an IV infusion Q4W or Q3W.
Blood and lymphatic system disorders Anaemia	50.0% 38/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	41.4% 60/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Leukopenia	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Neutropenia	19.7% 15/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	22.1% 32/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Thrombocytopenia	21.1% 16/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.0% 16/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Dry eye	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Eye disorders Lacrimation increased	3.9% 3/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 9/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal distension	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.69% 1/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.0% 13/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	35.5% 27/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	34.5% 50/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	18.4% 14/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.9% 26/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dyspepsia	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 8/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dysphagia	7.9% 6/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.4% 5/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastrooesophageal reflux disease	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	44.7% 34/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	44.1% 64/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Stomatitis	7.9% 6/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 7/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	18.4% 14/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	24.1% 35/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Asthenia	10.5% 8/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	16.6% 24/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	43.4% 33/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	46.2% 67/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Mucosal inflammation	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 8/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema peripheral	22.4% 17/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.9% 26/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pain	9.2% 7/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.9% 10/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	11.8% 9/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	15.9% 23/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Nasopharyngitis	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Oral candidiasis	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.4% 5/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.9% 10/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.6% 11/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Fall	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Aspartate aminotransferase increased	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood creatinine increased	3.9% 3/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.3% 12/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Platelet count decreased	10.5% 8/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.7% 14/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight decreased	13.2% 10/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 8/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Decreased appetite	30.3% 23/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	23.4% 34/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypercalcaemia	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.4% 5/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperglycaemia	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypocalcaemia	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	16.6% 24/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypokalaemia	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 8/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypomagnesaemia	15.8% 12/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	11.7% 17/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyponatraemia	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.1% 3/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypophosphataemia	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.6% 11/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	9.2% 7/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	7.6% 11/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	19.7% 15/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.8% 20/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscle spasms	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 9/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.9% 10/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Pain in extremity	9.2% 7/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.7% 14/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	9.2% 7/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	13.8% 20/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dysgeusia	14.5% 11/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 8/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	10.5% 8/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	16.6% 24/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Neuropathy peripheral	11.8% 9/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	3.4% 5/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Paraesthesia	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 8/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Anxiety	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	9.7% 14/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Depression	7.9% 6/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	1.4% 2/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Insomnia	9.2% 7/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	8.3% 12/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	21.1% 16/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	17.9% 26/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	23.7% 18/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	24.1% 35/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	5.5% 8/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Haemoptysis	7.9% 6/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.9% 10/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Hiccups	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.8% 7/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Productive cough	2.6% 2/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 9/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Alopecia	7.9% 6/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	6.2% 9/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Dry skin	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.1% 6/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash	10.5% 8/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	12.4% 18/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	6.6% 5/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	2.8% 4/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Herpes zoster	5.3% 4/76 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/145 • From first dose of study drug to the end of study date; the median (min, max) duration was 10.0 (0.2, 41.4) and 9.4 (0.2, 42.9) months for Placebo and Denosumab respectively. Data are included for all participants who received at least one dose of study drug. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER