A Study of Alpharadin With Docetaxel in Patients With Bon... | NCT01106352

NCT01106352

ID	Type	Description	Link
BC1-10	Other Identifier	Algeta ASA
2011-000822-31	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Radium-223 dichloride (Xofigo, BAY88-8223) + docetaxel	Experimental	Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection. In the randomized phase IIa part of the protocol, the dose established in the dose-escalation part of the protocol (Phase I) will be used, i.e. 5 doses of 50 kBq/kg b.w. every 6 weeks in combination with the approved step-down dose of docetaxel (60 mg/m^2) administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone.	Drug: Radium-223 dichloride (Xofigo, BAY88-8223) Drug: Docetaxel
Docetaxel	Active Comparator	Docetaxel (75 mg/m2) will be administered intravenously every 3 weeks with 5 mg prednisone twice a day continuously and pre-medication with dexamethasone. Step-down to 60 mg/m^2 is allowed as per the approved docetaxel label.	Drug: Docetaxel

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Radium-223 dichloride (Xofigo, BAY88-8223)	Drug	Alpharadin (Radium-223 dichloride) is administered intravenously as a bolus injection.	Radium-223 dichloride (Xofigo, BAY88-8223) + docetaxel

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part	DLT was defined as - Absolute neutrophil count grade greater than or equal to (>=) 4 (Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0: less than [<] 0.5 × 109 per Liter) lasting longer than 7 days without fever despite granulocyte colony-stimulating factor (G-CSF) support). Platelet count Grade >= 4 (CTCAE, v4.0: < 25× 109/L) lasting longer than 7 days. Diarrhea Grade >= 3 (CTAE, v4.0: increase of >= 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care in activities of daily living) in spite of optimal use of antidiarrheal medication. Vomiting or constipation Grade >= 4 (CTCAE, v4.0: life-threatening consequences; urgent intervention indicated). Febrile neutropenia Grade >= 3 (CTCAE, v4.0).	From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part
Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4	Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in patient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.	From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs
Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period	In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Other Outcomes

Measure	Description	Time Frame
Exploratory Efficacy: Weighted Mean Area Under the Curve for Bone Turnover Biomarkers	Weighted mean area under the curve for the below bone turnover biomarkers were evaluated, ICTP = pyridinoline cross-linked carboxyterminal telopeptide P1NP = N-terminal peptide of procollagen type 1 uCTX-1 = urine C-telopeptide 1	From start of study treatment to 6 weeks after study treatment (maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the prostate.
Two or more bone metastases (hot spots) confirmed by bone scintigraphy within 8 weeks prior to study entry
Known castration-resistant disease
Karnofsky Performance Status (KPS): ≥70% within 14 days before start of study treatment (ECOG 1)
Life expectancy at least 6 months.
Acceptable hematology and serum biochemistry screening values
Eligible for use of docetaxel according to the product information (package insert or similar).

Exclusion Criteria:

Has received an investigational therapeutic drug within the last 4 weeks prior to start of study treatment, or is scheduled to receive one during the treatment period.
Has received external radiotherapy within the last 4 weeks prior to start of study treatment.
Has an immediate need for radiotherapy.
Has received prior hemibody external radiotherapy .
Has received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases.
Has received cytotoxic chemotherapy within the last 4 weeks prior to start of study treatment, or has not recovered to grade 1 or 0 from adverse events due to cytotoxic chemotherapy administered more than 4 weeks earlier.
Has received more than ten previous infusions of docetaxel.
Previous known experience of grade ≥ 3 docetaxel related toxicities or docetaxel toxicity related dose interruption or discontinuation.
Previous use of G-CSF for persistent neutropenia after docetaxel treatment.
Has received blood transfusion or erythropoietin (EPO) within the last 4 weeks prior to start of study treatment.
Has received prior treatment with Alpharadin.
Malignant lymphadenopathy exceeding 3 cm in short-axis diameter.
Symptomatic nodal disease, i.e. scrotal, penile or leg edema.
Visceral metastases from CRPC (>2 lung and/or liver metastases [size ≥2cm]), as assessed by CT scan or MRI of the chest/abdomen/pelvis within the last 8 weeks prior to start of study treatment.
Uncontrolled loco-regional disease.
Other primary tumor (other than CRPC) including haematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).
Has imminent or established spinal cord compression based on clinical findings and/or MRI.
Unmanageable fecal incontinence

Contacts/Locations Module

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		San Francisco	California	94115	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31082669	Derived	Morris MJ, Loriot Y, Sweeney CJ, Fizazi K, Ryan CJ, Shevrin DH, Antonarakis ES, Pandit-Taskar N, Deandreis D, Jacene HA, Vesselle H, Petrenciuc O, Lu C, Carrasquillo JA, Higano CS. Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: a phase 1 dose escalation/randomised phase 2a trial. Eur J Cancer. 2019 Jun;114:107-116. doi: 10.1016/j.ejca.2019.04.007. Epub 2019 May 11.
26854432

Label	URL
Click here to find information about studies related to Bayer Healthcare products conducted in Europe.	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
BG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
BG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
BG003	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
BG004	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.
BG005	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Number

participants

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020

Primary

Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4

Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An Serious Adverse Event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in patient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment.

Only participants who received treatment were assessed

Posted

Number

Participants

From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.

Primary

Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only randomized participants who have this outcome measure tested were assessed

Posted

Mean

Standard Deviation

gram per liter (G/L)

Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

units per liter (U/L)

Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

micromole(s)/litre

Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

millimole(s)/liter

Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

giga per liter (GI/L)

Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

tetra per liter (TI/L)

Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

millimeters of mercury (mmHg)

From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Changes From Baseline in Respiratory Rate During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

breaths/min

From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation

Primary

Changes From Baseline in Heart Rate During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

beats per min

From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Changes From Baseline in Weight During the Treatment Period

In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group.

Only participants who received treatment were assessed

Posted

Mean

Standard Deviation

kilogram(s)

From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.
OG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Number of Subjects With Physical Examination During the Treatment Period

Any physical examination finding that was classified by the investigator as a clinically significant change (compared with previous examination) was considered an AE, documented on the eCRF, and followed until the outcome was known. The below physical examination findings were recorded and reported. GDASC = General disorders and administration site conditions MND = Metabolism and nutrition disorders SSTD= Skin and subcutaneous tissue disorders MCTD = Musculoskeletal and connective tissue disorders IPPC = Injury, poisoning and procedural complications RTMD = Respiratory, thoracic and mediastinal disorders NBMU = Neoplasms benign, malignant and unspecified (include cysts and polyps) In the below table.

Only participants who received treatment were assessed

Posted

Number

Participants

From start of study treatment to 6 weeks after study treatment (i.e., maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 mg/m^2 every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation.
OG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation

Primary

Number of Subjects With Signs of Long-Term Radiation Toxicity

Long-term radiation toxicity included incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukemia, myelodysplastic syndrome, and aplastic anemia).

Only participants who received treatment were assessed

Posted

Number

Participants

From start of study treatment upto 12 months

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Units	Counts
Participants	OG000

Other Pre-specified

Exploratory Efficacy: Weighted Mean Area Under the Curve for Bone Turnover Biomarkers

Weighted mean area under the curve for the below bone turnover biomarkers were evaluated, ICTP = pyridinoline cross-linked carboxyterminal telopeptide P1NP = N-terminal peptide of procollagen type 1 uCTX-1 = urine C-telopeptide 1

Subjects included in the per protocol: All subjects in the ITT population who received at least 40% of the specified number of administrations of radium-223 dichloride (in the radium-223 dichloride cohort) or of docetaxel (in the docetaxel cohort), and who did not have any major protocol violations.

Posted

Mean

Standard Deviation

mcg/L

From start of study treatment to 6 weeks after study treatment (maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Other Pre-specified

Exploratory Efficacy: Time to Prostate-specific Antigen (PSA) Progression

Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least 1 week apart.

Posted

Median

95% Confidence Interval

days

12 months

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Units	Counts
Participants

Other Pre-specified

Exploratory Efficacy: Percent Change From Baseline in Circulating Tumor Cells at Day 85

CTCs were measured to follow the evolution of the level of CTCs after treatment.

Posted

Mean

Standard Deviation

Percent Change

Baseline, Day 85, expanded safety cohort

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Units	Counts
Participants

Other Pre-specified

Exploratory Efficacy: Time to Clinical or Radiographic Progression

Time to first radiologic or clinical progression is determined by one of the following:

For soft tissue lesions, the determination is based on Response Evaluation Criteria in Solid Tumors 1.1.
For bone disease, the determination is based on Prostate Cancer Working Cohort 2 (PCWG2) definitions, which require the appearance of at least 2 new lesions with a confirmatory bone scan at least 6 or more weeks later. For clinical progression, the investigators followed the recommendations of the PCWG25 and used their clinical judgment to determine clinical progression.

Posted

Median

95% Confidence Interval

days

From start of study treatment to 12 months, at every 12 weeks

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Other Pre-specified

Progression Free Survival (PFS) End Point

PFS defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (radiological or clinical, whichever was earlier) or death (if death occurred before progression was documented). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation.

Posted

Median

95% Confidence Interval

days

From start of study treatment to 12 months, at every 12 weeks

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Other Pre-specified

Overall Survival Rate

The overall survival (OS) time in days was calculated as number of days since the day of first dose of study medication until the date of death.

Posted

Median

95% Confidence Interval

days

12 months

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Units	Counts
Participants

Other Pre-specified

Number of Subjects Who Responded to Interactive Voice Response System (IVRS) Pain

The subject completed the full BPI (short form) paper questionnaire, and clinical staff completed the analgesic log. The test consists of 10 questions addressing severity, location, chronicity, and amount of relief. In question 3, subjects with pain are asked to evaluate the severity of pain at worst in the past 24 hours in a 0 to 10 scale, with 0 indicating no pain, and 10 indicating the worst pain.

Posted

Number

Participants

From start of study treatment until 12 months

ID	Title	Description
OG000	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.
OG001	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin (Radium [Ra]-223 dichloride, BAY88-8223) at a dose of 25 kBq/kg body weight based on National Institute of Standards and Technology (NIST) 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 75 milligram per square meter (mg/m^2) every three weeks; unless dose limiting toxicity (DLT) or other safety concerns limited the dose escalation	4	7	7	7
EG001	Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 25 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.	0	3	3	3
EG002	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation	Subjects received two intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks; unless DLT or other safety concerns limited the dose escalation.	2	7	7	7
EG003	Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort	Subjects received five intravenous injections of Alpharadin at a dose of 50 kBq/kg body weight based on NIST 2010 standardization, separated by an interval of six weeks in combination with docetaxel at 60 mg/m^2 every three weeks.	7	33	33	33
EG004	Docetaxel 75 mg/m^2 - Safety Cohort	Subjects received docetaxel at 75 mg/m^2 twice daily every three weeks	4	13	13	13

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 events2 affected7 at risk EG0010 events0 affected3 at risk EG0022 events2 affected7 at risk EG0030 events0 affected33 at risk EG004
Leukopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Blindness unilateral	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Chest pain	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pneumonia	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Skin infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Biopsy lymph gland	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Syncope	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Embolism	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Hypotension	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG0033 events3 affected33 at risk EG0041 events1 affected13 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 events2 affected7 at risk EG0012 events2 affected3 at risk EG0025 events5 affected7 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Palpitations	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Dry eye	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Lacrimation increased	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Ocular hypertension	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Vision blurred	Eye disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Anorectal discomfort	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected3 at risk EG0023 events2 affected7 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0005 events5 affected7 at risk EG0014 events2 affected3 at risk EG0025 events5 affected7 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Melaena	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0004 events3 affected7 at risk EG0012 events1 affected3 at risk EG0023 events2 affected7 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Tongue ulceration	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 events3 affected7 at risk EG0010 events0 affected3 at risk EG0023 events2 affected7 at risk EG003
Asthenia	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Chest discomfort	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Chest pain	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Face oedema	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Facial pain	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Fatigue	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0005 events5 affected7 at risk EG0013 events3 affected3 at risk EG0024 events4 affected7 at risk EG003
Influenza like illness	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Injection site reaction	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Mucosal dryness	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Mucosal inflammation	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Oedema	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Oedema peripheral	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pain	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Pyrexia	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Swelling	General disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Hepatomegaly	Hepatobiliary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Bronchitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Cellulitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Fungal infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Herpes virus infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Hordeolum	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Oral infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pneumonia	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Rectal abscess	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Rhinitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Sinusitis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Tinea pedis	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Accident	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Limb injury	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Radiation proctitis	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Subcutaneous haematoma	Injury, poisoning and procedural complications	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Blood pressure increased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Haemoglobin decreased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Respiratory rate increased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Weight decreased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
White blood cell count decreased	Investigations	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Insulin resistance	Metabolism and nutrition disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0021 events1 affected7 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0004 events4 affected7 at risk EG0012 events1 affected3 at risk EG0021 events1 affected7 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0012 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0023 events3 affected7 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Balance disorder	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Dizziness	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0022 events2 affected7 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Headache	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Lethargy	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Memory impairment	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Myoclonus	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0022 events2 affected7 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0014 events3 affected3 at risk EG0020 events0 affected7 at risk EG003
Sciatica	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Visual field defect	Nervous system disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Agitation	Psychiatric disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Incontinence	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Ureteric obstruction	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Urethral pain	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Urinary incontinence	Renal and urinary disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Penile pain	Reproductive system and breast disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Priapism	Reproductive system and breast disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0003 events3 affected7 at risk EG0011 events1 affected3 at risk EG0023 events3 affected7 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0011 events1 affected3 at risk EG0023 events3 affected7 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0002 events2 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Ecchymosis	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Nail bed disorder	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Nail dystrophy	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Nail toxicity	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0012 events1 affected3 at risk EG0020 events0 affected7 at risk EG003
Skin atrophy	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Skin striae	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Flushing	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0001 events1 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Hot flush	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Hypotension	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0021 events1 affected7 at risk EG003
Vascular pain	Vascular disorders	MedDRA (18.0)	Non-systematic Assessment	EG0000 events0 affected7 at risk EG0010 events0 affected3 at risk EG0020 events0 affected7 at risk EG003

The radium 223 dichloride treatment was calculated as 50 kBq per NIST 2010, and would be approximately 55 kBq per NIST 2015 standard. Pharmacokinetic endpoint was deleted as no PK variables were evaluated in the study.

Certain Agreements

ID	Term
C581106	radium Ra 223 dichloride
D000077143	Docetaxel

Ancestor Terms

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes

Units	Counts
Participants	OG00032 OG00113

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events2 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events2 affected13 at risk

EG0040 events0 affected13 at risk

EG0045 events5 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events2 affected13 at risk

EG0043 events2 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0046 events5 affected13 at risk

EG0049 events5 affected13 at risk

EG0042 events2 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0044 events4 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG00413 events8 affected13 at risk

EG0040 events0 affected13 at risk

EG0043 events3 affected13 at risk

EG0042 events2 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0043 events2 affected13 at risk

EG0042 events2 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG00415 events9 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events1 affected13 at risk

EG0043 events2 affected13 at risk

EG0042 events1 affected13 at risk

EG0049 events5 affected13 at risk

EG0042 events2 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events1 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0043 events1 affected13 at risk

EG0046 events4 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0042 events2 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events2 affected13 at risk

EG0041 events1 affected13 at risk

EG00410 events6 affected13 at risk

EG0045 events4 affected13 at risk

EG0042 events2 affected13 at risk

EG0042 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0045 events3 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0042 events2 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0042 events2 affected13 at risk

EG00412 events8 affected13 at risk

EG0045 events3 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0040 events0 affected13 at risk

EG0045 events4 affected13 at risk

EG0040 events0 affected13 at risk

EG0041 events1 affected13 at risk

EG0043 events2 affected13 at risk

EG0040 events0 affected13 at risk

EG0042 events2 affected13 at risk

EG0040 events0 affected13 at risk