Study of AMG 162 in Subjects With Advanced Cancer Current... | NCT00104650

Label	Type	Description	Intervention Names
IV Bisphosphonates q 4 weeks	Active Comparator	This is an open-label randomization to receive IV bisphosphonate (administered per package insert) every 4 weeks during the treatment phase. If subjects are enrolled into the extension phase, they will receive AMG 162 180mg (SC) every 4 weeks.	Drug: IV Bisphosphonate q 4 weeks
180 mg AMG 162 (SC) q 12 weeks	Experimental	This is an open-label randomization to receive 180 mg AMG 162 (SC) every 12 weeks during the treatment phase. If subjects are enrolled into the extension phase, they will continue to receive 180 mg AMG 162 (SC) every 12 weeks.	Genetic: AMG 162 180 mg (SC) q 12 weeks
180 mg AMG 162 (SC) q 4 weeks	Experimental	This is an open-label randomization to receive 180 mg AMG 162 (SC) every 4 weeks during the treatment phase. If subject is enrolled into the extension phase, they will continue to receive 180 mg AMG 162 (SC) every 4 weeks.	Genetic: AMG 162- 180 mg q 4 weeks

Name	Type	Description	Arm Group Labels	Other Names
AMG 162 180 mg (SC) q 12 weeks	Genetic	A 180 mg AMG 162 (SC) administered every 12 weeks for 2 doses (Day 1 and wk 13) in the treatment phase. If subjected are enrolled in the extension phase, they will continue to receive a 180 mg AMG 162 (SC) administered every 12 weeks for 9 doses.

Measure	Description	Time Frame
uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 13	Urinary N-telopeptide (uNTx) corrected by creatinine (uNTx/Cr) < 50 nmol/mmol at week 13.	13 weeks

Measure	Description	Time Frame
uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25	Urinary N-telopeptide (uNTX) corrected by creatinine < 50 nmol/mmol at week 25.	25 weeks
Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25

Name	Affiliation	Role
MD	Amgen	Study Director

PubMed Identifier	Type	Citation	Retractions
19237632	Result	Fizazi K, Lipton A, Mariette X, Body JJ, Rahim Y, Gralow JR, Gao G, Wu L, Sohn W, Jun S. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009 Apr 1;27(10):1564-71. doi: 10.1200/JCO.2008.19.2146. Epub 2009 Feb 23.
19524963

Label	URL
AmgenTrials clinical trials website	View source

ID	Title	Description
FG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
FG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)

ID	Title	Description
BG000	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)
BG001	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
BG002	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG00038 BG00137 BG00236 BG003111

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 13

Urinary N-telopeptide (uNTx) corrected by creatinine (uNTx/Cr) < 50 nmol/mmol at week 13.

All participants who are randomized to the treatment phase, receive at least one dose of treatment phase investigational product, and have treatment phase baseline measurements of uNTx and at least one treatment phase post-baseline measurement of uNTx.

Posted

Number

Participants

13 weeks

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Units	Counts
Participants	OG00035 OG00133 OG00236

Title

Denominators

Categories

Title	Measurements
	OG00010 OG00121 OG00228

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002		Cochran-Mantel-Haenszel	Adjusted for cancer type stratification factor	<0.001		Odds Ratio (OR)	12.28				95	3.35	45.03				No	Superiority or Other
OG000 OG001		Cochran-Mantel-Haenszel

Secondary

uNTx (Corrected by Creatinine) < 50 Nmol/mmol at Week 25

Urinary N-telopeptide (uNTX) corrected by creatinine < 50 nmol/mmol at week 25.

Posted

Number

Participants

25 weeks

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Units	Counts
Participants

Secondary

Percent Change of uNTx (Corrected by Creatinne) From Baseline to Week 25

Percent change from baseline to week 25 urinary N-telopeptide (uNTX) calculated using ((week 25 value - baseline value) / baseline value ) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline, week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Units	Counts

Secondary

Time to Reduction of uNTX (Corrected by Creatinine) to <50nmol/mmol

Kaplan-Meier estimate of the median time from enrollment to the 1st occurrence of uNTx below 50 nmol BCE/mmol (corrected by creatinine) up to week 25. For participants whose uNTx does not go below 50 nM BCE/mM creatinine, the time is censored at time of last evaluation of uNTx by week 25.

Posted

Median

Inter-Quartile Range

Days

Day 1, week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Secondary

Duration of Maintaining uNTX (Corrected by Creatinine) < 50nmol/mmol

Time from the 1st occurrence of uNTx below 50 nmol BCE/mmol (corrected by creatinine) to the 1st occurrence of uNTx above 50 nmol BCE/mmol up to week 25. For participants who remained below 50 nmol BCE/mmol, the time is censored at the time of last evaluation of uNTx up to week 25.

Treatment Phase Primary Analysis Subset. Median was not reached in at least 1 treatment arm. In lieu of the median, the number of subject whose uNTX (corrected by creatinine) less than 50nmol/mmol is presented.

Posted

Number

Participants

Day 1, week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Secondary

Percent Change of Serum CTX From Baseline to Week 25

Percent change from baseline to week 25 in Type I serum C-Telopeptide (CTX), calculated using ((week 25 value - baseline value) / baseline value ) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline, week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Units	Counts

Secondary

Time to First Skeletal Related Event

Time from study day 1 to first Skeletal Related Event (SRE), defined as >1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes).

All participants exposed to investigational product during the treatment phase. Median was not reached in at least 1 treatment arm. In lieu of the median, the number of subject who experienced a skeletal related event is presented.

Posted

Number

Participants

Day 1, week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Units	Counts

Secondary

Skeletal Related Events

Skeletal Related Event (SRE), defined as >1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes).

All participants exposed to investigational product during the treatment phase.

Posted

Number

Participants

Day 1, week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Units	Counts
Participants

Secondary

Hypercalcemia

Occurrence of hypercalcemia at grade 3 or 4 according to CTCAE v3 criteria

Posted

Number

Participants

Day 1, week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open-label intravenous (IV) bisphosphonate once every 4 weeks (Q4W)
OG001	Denosumab 180 mg Q12W	Open-label denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W)
OG002	Denosumab 180 mg Q4W	Open-label denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W)

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0014 affected35 at risk EG0024 affected38 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0012 affected35 at risk EG0022 affected38 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0012 affected35 at risk EG0023 affected38 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Pericardial effusion	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Diplopia	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Ascites	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0012 affected35 at risk EG0020 affected38 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Subileus	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Death	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
General physical health deterioration	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0013 affected35 at risk EG0021 affected38 at risk
Obstruction	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Cholangitis acute	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Hepatomegaly	Hepatobiliary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Bronchopneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Catheter related infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Lung infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Pneumonia	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Urinary tract infection staphylococcal	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Brain contusion	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0012 affected35 at risk EG0021 affected38 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0012 affected35 at risk EG0020 affected38 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected35 at risk EG0012 affected35 at risk EG0021 affected38 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0003 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Multiple myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0012 affected35 at risk EG0023 affected38 at risk
Prostate cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Vaginal cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Areflexia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Epiduritis	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Facial paresis	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Loss of consciousness	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Spinal cord compression	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Anxiety	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Confusional state	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Hallucination	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Dysuria	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Haematuria	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Kidney enlargement	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Renal failure	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Renal tubular necrosis	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Urinary retention	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Scar	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Radiotherapy to bone	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Hypertension	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Neurogenic shock	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Thrombosis	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected35 at risk EG0014 affected35 at risk EG0027 affected38 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0012 affected35 at risk EG0023 affected38 at risk
Angina pectoris	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0012 affected35 at risk EG0020 affected38 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Conjunctivitis	Eye disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0012 affected35 at risk EG0022 affected38 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0013 affected35 at risk EG0021 affected38 at risk
Constipation	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0006 affected35 at risk EG0017 affected35 at risk EG0027 affected38 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0015 affected35 at risk EG0025 affected38 at risk
Gastritis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected35 at risk EG0018 affected35 at risk EG0029 affected38 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0013 affected35 at risk EG0023 affected38 at risk
Vomiting	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0006 affected35 at risk EG0015 affected35 at risk EG0022 affected38 at risk
Asthenia	General disorders	MedDRA 10.0	Systematic Assessment	EG0007 affected35 at risk EG0018 affected35 at risk EG0027 affected38 at risk
Chills	General disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected35 at risk EG0010 affected35 at risk EG0021 affected38 at risk
Fatigue	General disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0013 affected35 at risk EG0025 affected38 at risk
Mucosal inflammation	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Oedema peripheral	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0015 affected35 at risk EG0026 affected38 at risk
Pyrexia	General disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0025 affected38 at risk
Bronchitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Influenza	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0011 affected35 at risk EG0022 affected38 at risk
Pharyngitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0012 affected35 at risk EG0020 affected38 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Urinary tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0012 affected35 at risk EG0025 affected38 at risk
Weight decreased	Investigations	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0012 affected35 at risk EG0022 affected38 at risk
Anorexia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0013 affected35 at risk EG0024 affected38 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0011 affected35 at risk EG0023 affected38 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0013 affected35 at risk EG0024 affected38 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0012 affected35 at risk EG0024 affected38 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected35 at risk EG0014 affected35 at risk EG0024 affected38 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0009 affected35 at risk EG00112 affected35 at risk EG0028 affected38 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0011 affected35 at risk EG0023 affected38 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0012 affected35 at risk EG0022 affected38 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0013 affected35 at risk EG0021 affected38 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected35 at risk EG0012 affected35 at risk EG0022 affected38 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected35 at risk EG0015 affected35 at risk EG0022 affected38 at risk
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0013 affected35 at risk EG0022 affected38 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0023 affected38 at risk
Paraesthesia	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0003 affected35 at risk EG0014 affected35 at risk EG0026 affected38 at risk
Anxiety	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Depression	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0005 affected35 at risk EG0013 affected35 at risk EG0021 affected38 at risk
Insomnia	Psychiatric disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0011 affected35 at risk EG0022 affected38 at risk
Haematuria	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected35 at risk EG0012 affected35 at risk EG0022 affected38 at risk
Pollakiuria	Renal and urinary disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk
Gynaecomastia	Reproductive system and breast disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0011 affected35 at risk EG0020 affected38 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0012 affected35 at risk EG0020 affected38 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0014 affected35 at risk EG0021 affected38 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected35 at risk EG0014 affected35 at risk EG0021 affected38 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0011 affected35 at risk EG0021 affected38 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Radiotherapy to bone	Surgical and medical procedures	MedDRA 10.0	Systematic Assessment	EG0002 affected35 at risk EG0010 affected35 at risk EG0020 affected38 at risk
Hypertension	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected35 at risk EG0010 affected35 at risk EG0022 affected38 at risk

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders
D014652	Vascular Diseases
D002318	Cardiovascular Diseases
D010265	Paraproteinemias
D001796	Blood Protein Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006474	Hemorrhagic Disorders
D008232	Lymphoproliferative Disorders
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D003746	Dental Enamel Proteins

ID	Title	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bisphosphonate IV Q4W	19	35	33	35
EG001	Denosumab 180 mg Q12W	16	35	29	35
EG002	Denosumab 180 mg Q4W	21	38	29	38