Trial Outcomes & Findings for Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium (NCT NCT00896454)

Last Updated: 2018-10-17

Results Overview

Response is defined as corrected serum calcium (CSC) ≤ 11.5 mg/dL, within 10 days after the first dose of denosumab. For all CSC values, if albumin was \< 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium \[mg/dL\] + (0.8 x (4 - serum albumin \[g/dL\]))

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

33 participants

Primary outcome timeframe

10 days

Results posted on

2018-10-17

Participant Flow

First patient was enrolled on 16 November 2009 and the last patient enrolled on 02 July 2012. Data are reported as of the primary analysis cut-off date of 13 September 2012.

Participant milestones

Participant milestones
Measure	Denosumab Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Overall Study STARTED	33
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Denosumab Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Overall Study Death	10
Overall Study Adverse Event	8
Overall Study Disease Progression	5
Overall Study Other	4
Overall Study Requirement for alternative therapy	3
Overall Study Ongoing in study	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Study of Denosumab in the Treatment of Hypercalcemia of Malignancy in Subjects With Elevated Serum Calcium

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Age, Continuous	60.3 years STANDARD_DEVIATION 14.8 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	23 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	1 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	7 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	14 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 3	8 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 4	3 participants n=5 Participants
Primary Tumor Type Bladder	1 participants n=5 Participants
Primary Tumor Type Breast	6 participants n=5 Participants
Primary Tumor Type Head and neck	2 participants n=5 Participants
Primary Tumor Type Liver	1 participants n=5 Participants
Primary Tumor Type Neuroendocrine/carcinoid	4 participants n=5 Participants
Primary Tumor Type Non-hodgkin's	2 participants n=5 Participants
Primary Tumor Type Non-small cell lung cancer	3 participants n=5 Participants
Primary Tumor Type Ovarian	1 participants n=5 Participants
Primary Tumor Type Renal	3 participants n=5 Participants
Primary Tumor Type Small cell lung cancer	1 participants n=5 Participants
Primary Tumor Type Soft tissue sarcoma	1 participants n=5 Participants
Primary Tumor Type Unknown (primary tumor)	1 participants n=5 Participants
Primary Tumor Type Multiple myeloma	3 participants n=5 Participants
Primary Tumor Type Chronic lymphocytic leukemia	2 participants n=5 Participants
Primary Tumor Type IGG kappa multiple myeloma	1 participants n=5 Participants
Primary Tumor Type Myeloma	1 participants n=5 Participants
Time from initial cancer diagnosis to enrollment	56.9 months STANDARD_DEVIATION 68.8 • n=5 Participants
Presence of metastatic disease at enrollment Yes	30 participants n=5 Participants
Presence of metastatic disease at enrollment No	3 participants n=5 Participants
Presence of bone metastatic disease at enrollment Yes	13 participants n=5 Participants
Presence of bone metastatic disease at enrollment No	20 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Fatigue	9 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Anorexia	5 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Nausea	4 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Depressed level of consciousness	2 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Vomiting	2 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Dry mouth	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Constipation	4 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Lethargy	4 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Confusion	3 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Polyuria	2 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Abdominal pain	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Decreased mental acuity	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Dyspnea	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms General weakness	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Insomnolence	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Light headedness (dizziness)	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Listlessness/muscle weakness	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Polyuro-polydipsic syndrome	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Psychomotor retardation	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Retching	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Urinary frequency	1 participants n=5 Participants
Baseline Hypercalcemia of Malignancy (HCM) Symptoms Weight loss	1 participants n=5 Participants
Calcium (corrected)	13.89 mg/dL STANDARD_DEVIATION 1.27 • n=5 Participants

PRIMARY outcome

Timeframe: 10 days

Population: Response Analysis Subset including all participants who received at least 1 dose of denosumab and had a screening CSC (from local lab) \> 12.5 mg/dL (3.1 mmol/L).

Outcome measures

Outcome measures
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Percentage of Participants With a Response Within 10 Days of First Dose of Denosumab	63.6 percentage of participants Interval 45.1 to 79.6

SECONDARY outcome

Timeframe: Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

Population: Response Analysis Subset

Outcome measures

Outcome measures
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Percentage of Participants With a Response by Visit By Day 36	69.7 percentage of participants Interval 51.3 to 84.4
Percentage of Participants With a Response by Visit By Day 43	69.7 percentage of participants Interval 51.3 to 84.4
Percentage of Participants With a Response by Visit By Day 2	9.1 percentage of participants Interval 1.9 to 24.3
Percentage of Participants With a Response by Visit By Day 4	24.2 percentage of participants Interval 11.1 to 42.3
Percentage of Participants With a Response by Visit By Day 8	48.5 percentage of participants Interval 30.8 to 66.5
Percentage of Participants With a Response by Visit By Day 10	63.6 percentage of participants Interval 45.1 to 79.6
Percentage of Participants With a Response by Visit By Day 15	63.6 percentage of participants Interval 45.1 to 79.6
Percentage of Participants With a Response by Visit By Day 19	69.7 percentage of participants Interval 51.3 to 84.4
Percentage of Participants With a Response by Visit By Day 23	69.7 percentage of participants Interval 51.3 to 84.4
Percentage of Participants With a Response by Visit By Day 29	69.7 percentage of participants Interval 51.3 to 84.4
Percentage of Participants With a Response by Visit By Day 50	69.7 percentage of participants Interval 51.3 to 84.4
Percentage of Participants With a Response by Visit By Day 57	69.7 percentage of participants Interval 51.3 to 84.4

SECONDARY outcome

Timeframe: Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

Population: Response Analysis Subset

Response is defined as corrected serum calcium (CSC) ≤ 10.8 mg/dL (2.7 mmol/L). For all CSC values, if albumin was \< 4 g/dL, the following formula was used to calculate CSC: CSC = Total serum calcium \[mg/dL\] + (0.8 x (4 - serum albumin \[g/dL\])).

Outcome measures

Outcome measures
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Percentage of Participants With a Complete Response by Visit By Day 4	15.2 percentage of participants Interval 5.1 to 31.9
Percentage of Participants With a Complete Response by Visit By Day 10	36.4 percentage of participants Interval 20.4 to 54.9
Percentage of Participants With a Complete Response by Visit By Day 15	45.5 percentage of participants Interval 28.1 to 63.6
Percentage of Participants With a Complete Response by Visit By Day 29	51.5 percentage of participants Interval 33.5 to 69.2
Percentage of Participants With a Complete Response by Visit By Day 36	60.6 percentage of participants Interval 42.1 to 77.1
Percentage of Participants With a Complete Response by Visit By Day 2	3.0 percentage of participants Interval 0.1 to 15.8
Percentage of Participants With a Complete Response by Visit By Day 8	27.3 percentage of participants Interval 13.3 to 45.5
Percentage of Participants With a Complete Response by Visit By Day 19	45.5 percentage of participants Interval 28.1 to 63.6
Percentage of Participants With a Complete Response by Visit By Day 23	51.5 percentage of participants Interval 33.5 to 69.2
Percentage of Participants With a Complete Response by Visit By Day 43	63.6 percentage of participants Interval 45.1 to 79.6
Percentage of Participants With a Complete Response by Visit By Day 50	63.6 percentage of participants Interval 45.1 to 79.6
Percentage of Participants With a Complete Response by Visit By Day 57	63.6 percentage of participants Interval 45.1 to 79.6

SECONDARY outcome

Timeframe: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Population: Response Analysis Subset

Time to Response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) ≤ 11.5 mg/dL. Participants were censored on the last CSC assessment day if no response was observed. If there was no post-baseline CSC assessment, time to response was censored on study Day 1. Time to response was analyzed using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Time to Response	9.0 days Interval 5.0 to 19.0

SECONDARY outcome

Timeframe: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Population: Response Analysis Subset

Time to complete response was defined as the time period from study Day 1 to the first time post-baseline corrected serum calcium (CSC) was ≤ 10.8 mg/dL (2.7 mmol/L). Participants were censored on the last CSC assessment day if no complete response was observed. If there was no post-baseline CSC assessment, time to complete response was censored on study Day 1. Time to complete response was analyzed using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Time to Complete Response	23.0 days Interval 11.0 to 43.0

SECONDARY outcome

Timeframe: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Population: Participants with a response in the Response Analysis Subset

Duration of response is defined as the number of days from the first day of corrected serum calcium ≤ 11.5 mg/dL (2.9 millimoles/L) to the last day of corrected serum calcium ≤ 11.5 mg/dL. Participants were censored on the last CSC assessment day if their CSC level never reached \> 11.5 mg/dL after the first response. If a participant had no CSC assessment after the first response, duration of response was set to zero and censored. Duration of response was summarized for participants who achieved a response using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Denosumab n=23 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Duration of Response	104.0 days Interval 9.0 to Not estimable due to the low number of events

SECONDARY outcome

Timeframe: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Population: Participants with a complete response in the Response Analysis Subset

Duration of complete response is defined as the number of days from the first day of of corrected serum calcium ≤ 10.8 mg/dL (2.7 millimoles/L) to the last day of corrected serum calcium ≤ 10.8 mg/dL. Participants were censored on the last CSC assessment day if their CSC level never reached \> 10.8 mg/dL after the complete response. If a participant had no CSC assessment after the complete response, duration of complete response was set to zero and censored. Duration of complete response was summarized for participants who achieved a complete response using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Denosumab n=21 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Duration of Complete Response	34.0 days Interval 1.0 to 134.0

SECONDARY outcome

Timeframe: From Day 1 until the end of study date or primary data cutoff date (13 September 2012), whichever occured first; median time on study was 1.8 months.

Population: Response Analysis Subset

Time to relapse/nonresponse was defined as the number of days from study Day 1 until the last day of CSC ≤ 11.5 mg/dL for all particiipants with relapse after the first response. Participants were censored on the last CSC assessment day if their CSC level never reached \> 11.5 mg/dL after first response. For participants who never achieved response, time to relapse/nonresponse was set to zero. Otherwise, if there was no post-baseline CSC assessment, time to relapse/nonresponse was censored on study Day 1. Time to relapse/nonresponse was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Time to Relapse/Nonresponse of Hypercalcemia of Malignancy	19.0 days Interval 5.0 to 114.0

SECONDARY outcome

Timeframe: Baseline and Days 2, 4, 8, 10, 15, 19, 23, 29, 36, 43, 50 and 57

Population: Efficacy Analysis Subset included all participants who received at least 1 dose of denosumab. n = Number of participants who had non-missing data at Baseline and the time point of interest.

Outcome measures

Outcome measures
Measure	Denosumab n=33 Participants Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 19 (n = 22)	-0.64 mmol/L Interval -0.8 to -0.3
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 23 (n = 21)	-0.60 mmol/L Interval -0.85 to -0.4
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 2 (n = 32)	-0.13 mmol/L Interval -0.31 to 0.09
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 4 (n = 32)	-0.25 mmol/L Interval -0.44 to -0.14
Change From Baseline in Corrected Serum Calcium Change form Baseline to Day 8 (n = 27)	-0.43 mmol/L Interval -0.73 to -0.2
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 10 (n = 28)	-0.54 mmol/L Interval -0.77 to -0.25
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 15 (n = 24)	-0.51 mmol/L Interval -0.89 to -0.15
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 29 (n = 22)	-0.53 mmol/L Interval -0.75 to -0.3
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 36 (n = 20)	-0.61 mmol/L Interval -0.84 to -0.15
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 43 (n = 19)	-0.75 mmol/L Interval -0.98 to -0.1
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 50 (n = 15)	-0.83 mmol/L Interval -1.03 to -0.2
Change From Baseline in Corrected Serum Calcium Change from Baseline to Day 57 (n = 17)	-0.73 mmol/L Interval -1.03 to -0.25

Adverse Events

Denosumab 120 mg Q4W

Serious events: 29 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Denosumab 120 mg Q4W n=33 participants at risk Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
Blood and lymphatic system disorders Anaemia	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Pancytopenia	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Cardiac arrest	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Cardiac disorders Tachycardia	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Endocrine disorders Hypercalcaemia of malignancy	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Colitis	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Oesophageal obstruction	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pyrexia	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Hepatobiliary disorders Hepatic failure	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Septic shock	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Urine output decreased	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Failure to thrive	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypercalcaemia	15.2% 5/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypokalaemia	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyponatraemia	3.0% 1/33 • Median time on study was 1.8 months. 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) Bladder cancer	3.0% 1/33 • Median time on study was 1.8 months. 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) Breast cancer	3.0% 1/33 • Median time on study was 1.8 months. 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) Breast cancer metastatic	3.0% 1/33 • Median time on study was 1.8 months. 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) Chronic lymphocytic leukaemia	3.0% 1/33 • Median time on study was 1.8 months. 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) Diffuse large B-cell lymphoma	3.0% 1/33 • Median time on study was 1.8 months. 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) Gastrointestinal stromal tumour	3.0% 1/33 • Median time on study was 1.8 months. 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) Head and neck cancer	6.1% 2/33 • Median time on study was 1.8 months. 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) Hepatic neoplasm malignant	3.0% 1/33 • Median time on study was 1.8 months. 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	6.1% 2/33 • Median time on study was 1.8 months. 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) Multiple myeloma	6.1% 2/33 • Median time on study was 1.8 months. 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	6.1% 2/33 • Median time on study was 1.8 months. 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) Ovarian cancer	3.0% 1/33 • Median time on study was 1.8 months. 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) Renal cell carcinoma	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Lethargy	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Confusional state	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Mental status changes	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure acute	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal tubular necrosis	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Respiratory distress	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Respiratory failure	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	3.0% 1/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Other adverse events
Measure	Denosumab 120 mg Q4W n=33 participants at risk Participants received denosumab at a dose of 120 mg subcutaneously (SC) every 4 weeks (Q4W) with a loading dose of 120 mg SC on study Days 8 and 15.
General disorders Pyrexia	12.1% 4/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Pneumonia	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Anaemia	15.2% 5/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Febrile neutropenia	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Neutropenia	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Thrombocytopenia	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal distension	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	21.2% 7/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	21.2% 7/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dry mouth	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	30.3% 10/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	21.2% 7/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Asthenia	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	18.2% 6/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Oedema peripheral	24.2% 8/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Injury, poisoning and procedural complications Fall	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Haemoglobin decreased	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight decreased	12.1% 4/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Decreased appetite	21.2% 7/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Fluid overload	15.2% 5/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperkalaemia	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypocalcaemia	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypophosphataemia	12.1% 4/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Arthralgia	12.1% 4/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Back pain	12.1% 4/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Myalgia	9.1% 3/33 • Median time on study was 1.8 months. 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	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Depressed level of consciousness	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Headache	24.2% 8/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Confusional state	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Insomnia	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Cough	18.2% 6/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.2% 6/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Epistaxis	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pleural effusion	12.1% 4/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	12.1% 4/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Alopecia	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash	9.1% 3/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Rash pruritic	6.1% 2/33 • Median time on study was 1.8 months. Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Vascular disorders Hypotension	9.1% 3/33 • Median time on study was 1.8 months. 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

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