Multiple Dose Study to Evaluate the Safety of Multiple Do... | NCT01464931

Label	Type	Description	Intervention Names
Denosumab	Experimental	Participants received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.	Drug: Denosumab

Name	Type	Description	Arm Group Labels	Other Names
Denosumab	Drug	Adminstered by subcutaneous injection	Denosumab	XGEVA

Measure	Description	Time Frame
Number of Participants With Clinically Significant Hypocalcemia	Clinically significant hypocalcemia is defined as albumin-adjusted calcium < 7.0 mg/dL or symptomatic hypocalcemia. Symptomatic hypocalcemiais is defined as both a clinical adverse event of hypocalcemia and a concomitant symptom of hypocalcemia (e.g., hypoesthesia, paresthesia, muscle cramps, seizure, prolonged QT interval) that occurred along with the hypocalcemia event or decreased serum calcium levels.	113 days

Measure	Description	Time Frame
Number of Participants With Hypocalcemia Determined by CTCAE v.4.0 Criteria	The severity of hypocalcemia (a low concentration of calcium, corrected for albumin, in the blood) was graded according to the common terminology criteria for adverse events (CTCAE) v.4.0 criteria: Grade 1: albumin-adjusted serum calcium < lower limit of normal (LLN; 9.2 mg/dL) to 8.0 mg/dL; Grade 2: albumin-adjusted serum calcium < 8.0 to 7.0 mg/dL; Grade 3: albumin-adjusted serum calcium < 7.0 to 6.0 mg/dL; Grade 4: albumin-adjusted serum calcium < 6.0 mg/dL.

Name	Affiliation	Role
MD	Amgen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Tempe	Arizona	85284	United States
Research Site

Label	URL
AmgenTrials clinical trials website	View source

ID	Title	Description
FG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
FG001	ESRD

ID	Title	Description
BG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
BG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00016 BG00116 BG00232

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

Number of Participants With Clinically Significant Hypocalcemia

Clinically significant hypocalcemia is defined as albumin-adjusted calcium < 7.0 mg/dL or symptomatic hypocalcemia. Symptomatic hypocalcemiais is defined as both a clinical adverse event of hypocalcemia and a concomitant symptom of hypocalcemia (e.g., hypoesthesia, paresthesia, muscle cramps, seizure, prolonged QT interval) that occurred along with the hypocalcemia event or decreased serum calcium levels.

Safety Analysis Set (all participants who received at least 1 dose of denosumab)

Posted

Number

participants

113 days

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG00016 OG00116

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0012

Secondary

Number of Participants With Hypocalcemia Determined by CTCAE v.4.0 Criteria

The severity of hypocalcemia (a low concentration of calcium, corrected for albumin, in the blood) was graded according to the common terminology criteria for adverse events (CTCAE) v.4.0 criteria: Grade 1: albumin-adjusted serum calcium < lower limit of normal (LLN; 9.2 mg/dL) to 8.0 mg/dL; Grade 2: albumin-adjusted serum calcium < 8.0 to 7.0 mg/dL; Grade 3: albumin-adjusted serum calcium < 7.0 to 6.0 mg/dL; Grade 4: albumin-adjusted serum calcium < 6.0 mg/dL.

Safety analysis set

Posted

Number

participants

113 days

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants

Secondary

Number of Participants With Hypophosphatemia Determined by CTCAE v.4.0 Criteria

The severity of hypophosphatemia (a low concentration of phosphates in the blood) was graded according to the common terminology criteria for adverse events (CTCAE) v.4.0 criteria: Grade 1: < LLN (3 mg/dL) - 2.5 mg/dL; Grade 2: < 2.5 - 2.0 mg/dL; Grade 3: < 2.0 - 1.0 mg/dL; Grade 4: < 1.0 mg/dL.

Safety analysis set

Posted

Number

participants

113 days

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Hypomagnesemia Determined by CTCAE v.4.0 Criteria

The severity of hypomagnesemia (a low concentration of magnesium in the blood) was graded according to the common terminology criteria for adverse events (CTCAE) v.4.0 criteria: Grade 1: < LLN (1.5 mg/dL) - 1.2 mg/dL; Grade 2: < 1.2 - 0.9 mg/dL; Grade 3: < 0.9 - 0.7 mg/dL; Grade 4: < 0.7 mg/dL.

Safety analysis set

Posted

Number

participants

113 days

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Albumin-adjusted Serum Calcium Over Time

Safety analysis set with available data at each time point

Posted

Median

Inter-Quartile Range

percent change

Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Serum Phosphorus Over Time

Safety analysis set with available data at each time point

Posted

Median

Inter-Quartile Range

percent change

Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Serum Magnesium Over Time

Safety analysis set with available data at each time point

Posted

Median

Inter-Quartile Range

percent change

Baseline and Days 2, 3, 6, 8, 11, 15, 22, 29, 30, 31, 34, 36, 39, 43, 57, 71, 85, and 113

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adverse Events

The severity of each adverse event (AE) was graded using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. The investigator assessed whether AEs were possibly related to study drug by answering the question: "Is there a reasonable possibility that the event may have been caused by the investigational product?" Abnormal laboratory findings without clinical significance (based on the investigator's judgment) were not recorded as AEs, however, laboratory value changes that required treatment or adjustment in current therapy were considered AEs. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal, • life-threatening (places the participant at immediate risk of death), • requires in-patient hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, • congenital anomaly/birth defect, and/or • other medically important serious event.

Safety analysis set

Posted

Number

participants

113 days

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Secondary

Maximum Observed Serum Denosumab Concentration (Cmax)

Serum concentrations of denosumab were measured by an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 20 ng/mL.

Pharmacokinetic (PK) Parameter Analysis Set (all participants who received at least 1 dose of denosumab and for whom PK parameter estimates could be derived)

Posted

Mean

Standard Deviation

μg/mL

Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113

ID	Title	Description
OG000	Severe CKD - Dose 1	Participants with severe CKD received 120 mg denosumab administered subcutaneously on Day 1.
OG001	ESRD - Dose 1	Participants with ESRD requiring dialysis received 120 mg denosumab administered subcutaneously on Day 1.
OG002	Severe CKD - Dose 2	Participants with severe CKD received 120 mg denosumab administered subcutaneously on Day 29.
OG003	ESRD - Dose 2	Participants with ESRD requiring dialysis received 120 mg denosumab administered subcutaneously on Day 29.

Secondary

Time to Maximum Observed Serum Denosumab Concentration (Tmax)

Serum concentrations of denosumab were measured by an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantification (LLOQ) was 20 ng/mL.

PK Parameter Analysis Set

Posted

Median

Full Range

days

Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113

ID	Title	Description
OG000	Severe CKD - Dose 1	Participants with severe CKD received 120 mg denosumab administered subcutaneously on Day 1.
OG001	ESRD - Dose 1	Participants with ESRD requiring dialysis received 120 mg denosumab administered subcutaneously on Day 1.
OG002	Severe CKD - Dose 2	Participants with severe CKD received 120 mg denosumab administered subcutaneously on Day 29.
OG003	ESRD - Dose 2	Participants with ESRD requiring dialysis received 120 mg denosumab administered subcutaneously on Day 29.

Secondary

Area Under the Serum Concentration-time Curve From Time 0 to 4 Weeks (AUC0-4wks) After Dose 1

Estimated using the linear trapezoidal method.

PK Parameter Analysis Set

Posted

Mean

Standard Deviation

μg*day/mL

Days 1, 8, 15, and 29 (predose)

ID	Title	Description
OG000	Severe CKD - Dose 1	Participants with severe CKD received 120 mg denosumab administered subcutaneously on Day 1.
OG001	ESRD - Dose 1	Participants with ESRD requiring dialysis received 120 mg denosumab administered subcutaneously on Day 1.

Units	Counts
Participants	OG000

Secondary

Area Under the Serum Concentration-time Curve From Time 0 to 12 Weeks (AUC0-12wks) After Dose 2

Estimated using the linear trapezoidal method.

PK Parameter Analysis Set

Posted

Mean

Standard Deviation

μg*day/mL

Days 29 (predose), 36, 43, 57, 71, and 85

ID	Title	Description
OG000	Severe CKD - Dose 2	Participants with severe CKD received 120 mg denosumab administered subcutaneously on Day 29.
OG001	ESRD - Dose 2	Participants with ESRD requiring dialysis received 120 mg denosumab administered subcutaneously on Day 29.

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Serum C-Telopeptide Over Time

Pharmacodynamic Analysis Set (all participants who received at least 1 dose of denosumab and from whom baseline and at least 1 postbaseline value was collected)

Posted

Median

Inter-Quartile Range

percent change

Baseline and Days 1 and 29 (predose), and on Days 8, 15, 36, 43, 57, 71, 85, and 113

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG000

Secondary

Number of Participants Who Developed Anti-denosumab Antibodies

Safety analysis set

Posted

Number

participants

From Day 1 (predose) to Day 113

ID	Title	Description
OG000	Severe CKD	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.
OG001	ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Angina pectoris	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Pericarditis	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Ventricular extrasystoles	Cardiac disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Hearing impaired	Ear and labyrinth disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Hyperparathyroidism	Endocrine disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Hyperparathyroidism secondary	Endocrine disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected16 at risk EG0022 affected32 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Constipation	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected16 at risk EG0011 affected16 at risk EG0023 affected32 at risk
Sensitivity of teeth	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Sarcoidosis	Immune system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Nasopharyngitis	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Otitis media	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0012 affected16 at risk EG0022 affected32 at risk
Urinary tract infection	Infections and infestations	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Arteriovenous fistula site complication	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Vascular graft complication	Injury, poisoning and procedural complications	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Blood calcium decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Blood parathyroid hormone decreased	Investigations	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Electrocardiogram PR shortened	Investigations	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected16 at risk EG0013 affected16 at risk EG0025 affected32 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0002 affected16 at risk EG00110 affected16 at risk EG00212 affected32 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Paraesthesia	Nervous system disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Ingrowing nail	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Arterial stenosis	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Hypertension	Vascular disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0011 affected16 at risk EG0022 affected32 at risk

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital 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

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Denosumab 120 mg - Severe	Participants with severe chronic kidney disease (CKD; defined as creatinine clearance < 30 mL/min) received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.	1	16	10	16
EG001	Denosumab 120 mg - ESRD	Participants with end-stage renal disease (ESRD) requiring dialysis received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.	2	16	15	16
EG002	Denosumab 120 mg - All Subjects	Participants received two 120 mg doses of denosumab administered subcutaneously on Day 1 and Day 29.	3	32	25	32

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Ileitis	Gastrointestinal disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk
Asthenia	General disorders	MedDRA 15.0	Systematic Assessment	EG0001 affected16 at risk EG0010 affected16 at risk EG0021 affected32 at risk
Non-cardiac chest pain	General disorders	MedDRA 15.0	Systematic Assessment	EG0000 affected16 at risk EG0011 affected16 at risk EG0021 affected32 at risk