A Global Study to Compare the Effects of Fulvestrant and... | NCT01602380

NCT01602380

ID	Type	Description	Link
2011-006326-24	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
faslodex+placebo	Experimental	Blinded: Fulvestrant 500mg intramuscular injection (2x250mg) plus dummy Anastrozole tablets	Drug: faslodex 500mg Drug: arimidex dummy
arimidex +placebo	Active Comparator	Blinded: Anastrozole 1mg tablets plus dummy Fulvestrant intramuscular injection (2x0mg)	Drug: arimidex 1mg Drug: faslodex dummy

Name	Type	Description	Arm Group Labels	Other Names
faslodex 500mg	Drug	2 x intramuscular injections at day 1, 14, 28 and every 28 days thereafter	faslodex+placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Comparison of Progression-Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole	PFS was defined as the time from randomisation until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), surgery or radiotherapy to manage worsening of disease or death by any cause (in the absence of progression). Outcome measure is reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique.	Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until the earliest of disease progression evident, patient dies or has surgery/radiotherapy for their disease (up to approximately 38 months)

Secondary Outcomes

Measure	Description	Time Frame
Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events	OS was defined as the time from randomisation until death by any cause. The current OS data correspond to that of the final analysis and the outcome measure is reported as percentage of patients with events.	Baseline (Day 0) up to data cut-off for final analysis (up to approximately 116 months). Following disease progression, patients were to be contacted at 12 weekly intervals to determine survival status

Eligibility Module

Name	Affiliation	Role
Shankar S, MD	AstraZeneca	Study Director
John Robertson, MD	Graduate Medicine and Health School, University of Nottingham, UK	Principal Investigator
Matthew Ellis, DM	Washington University School of Medicine, USA	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Modesto	California	95355	United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
39772884	Derived	Robertson JFR, Shao Z, Noguchi S, Bondarenko I, Panasci L, Singh S, Subramaniam S, Ellis MJ. Fulvestrant Versus Anastrozole in Endocrine Therapy-Naive Women With Hormone Receptor-Positive Advanced Breast Cancer: Final Overall Survival in the Phase III FALCON Trial. J Clin Oncol. 2025 May;43(13):1539-1545. doi: 10.1200/JCO.24.00994. Epub 2025 Jan 7.
29574365

Label	URL
CSP redacted	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 milligrams (mg), administered as two 5 milliliters (mL) intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 17, 2021	Nov 6, 2023

Arm/Group Information

ID	Title	Description
BG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
BG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).
BG002	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, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00063.8± 9.86(38 to 87) BG00163.3± 10.38(36 to 90) BG00263.5± 10.12(36 to 90)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000230 BG001232 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0015 BG002

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

Comparison of Progression-Free Survival (PFS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole

PFS was defined as the time from randomisation until objective disease progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), surgery or radiotherapy to manage worsening of disease or death by any cause (in the absence of progression). Outcome measure is reported as median time from randomisation to PFS, calculated using the Kaplan-Meier technique.

The ITT analysis set included all randomised patients.

Posted

Median

95% Confidence Interval

Months

Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until the earliest of disease progression evident, patient dies or has surgery/radiotherapy for their disease (up to approximately 38 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
OG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

Units	Counts
Participants	OG000230 OG001232

Title

Denominators

Categories

Title	Measurements
	OG00016.6(13.83 to 20.99) OG00113.8(11.99 to 16.59)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	If the true PFS HR for comparison of fulvestrant vs. anastrozole was 0.69 (likely to correspond to a 45% prolongation of PFS) the study had 90% power to demonstrate a statistically significant difference for PFS with a one-sided type 1 error of 2.5% (two-sided 5%).	Log Rank	Stratified log-rank test with factors for prior chemotherapy for locally advanced or metastatic disease and measurable disease at baseline.	0.0486	2-sided p-value	Hazard Ratio (HR)	0.797			2-Sided	95	0.637	0.999			A hazard ratio < 1 favours fulvestrant.

Secondary

Comparison of Overall Survival (OS) in Patients Treated With Fulvestrant With Those Treated With Anastrozole; Percentage of Patients With Events

OS was defined as the time from randomisation until death by any cause. The current OS data correspond to that of the final analysis and the outcome measure is reported as percentage of patients with events.

The ITT analysis set included all randomised patients. Date of death of 2 participants were unknown in the Anastrozole 1mg arm, hence they were censored for OS analysis.

Posted

Number

Percentage of patients

Baseline (Day 0) up to data cut-off for final analysis (up to approximately 116 months). Following disease progression, patients were to be contacted at 12 weekly intervals to determine survival status

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
OG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

Secondary

Objective Response Rate (ORR) for Fulvestrant Treatment Versus Anastrozole Treatment

ORR was defined as the percentage patients with an objective response (i.e. those recording a partial response [PR] or complete response [CR]) at some point during the study, prior to disease progression. ORR was assessed in patients with measurable disease at baseline only. The determination of measurable disease at baseline was done using baseline RECIST data. CR was disappearance of all target lesions since baseline; was any pathological lymph nodes selected as target lesions (TL) to have a reduction in short axis to <10 millimeter. PR was at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.

Percentages for ORR were calculated based on the number of patients in the ITT analysis set (which included all randomised patients) who had measurable disease at baseline (n=193 for Fulvestrant arm and n=196 for Anastrozole arm).

Posted

Number

Percentage of participants

Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).

Secondary

Duration of Response (DoR) for Fulvestrant Treatment Versus Anastrozole Treatment

DoR was defined only for patients who had an objective response, as the time in days from date of first documentation of response (CR/PR) until date of disease progression. CR was disappearance of all target lesions since baseline; any pathological lymph nodes selected as TL to have a reduction in short axis to <10 mm. At least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.

Only patients in the ITT analysis set (which included all randomised patients), who also had an objective response and had measurable disease at baseline were included in the DoR analysis (n=89 for Fulvestrant arm and n=88 for Anastrozole arm).

Posted

Median

Inter-Quartile Range

Months

Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
OG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

Secondary

Expected Duration of Response (EDoR) for Fulvestrant Treatment Versus Anastrozole Treatment

EDoR was estimated using the formula EDoR = p Efp(x), where x = DoR, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65).

EDoR analysis was based on the number of patients in the ITT analysis set (which included all randomised patients) who had measurable disease at baseline (n=193 for Fulvestrant arm and n=196 for Anastrozole arm).

Posted

Number

Days

Baseline RECIST 1.1 assessments and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
OG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

Secondary

Clinical Benefit Rate (CBR) for Fulvestrant Treatment Versus Anastrozole Treatment

CBR was defined as the percentage of patients who had a clinical benefit (i.e. best objective response of CR, PR or stable disease), that was maintained for at least 24 weeks, prior to any evidence of progression. Note that a minimum duration of 22 weeks for CBR was applicable in the analysis (rather than 24 weeks) to allow for the protocolled window of +/-2 weeks.

The ITT analysis set included all randomised patients.

Posted

Number

Percentage of participants

Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
OG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

Secondary

Duration of Clinical Benefit (DoCB) for Fulvestrant Treatment Versus Anastrozole Treatment

DoCB was defined only for patients who had clinical benefit, as the time in days from date of randomisation until the date of disease progression.

Only patients in the ITT analysis set (which included all randomised patients) who also had a clinical benefit were included in the DoCB analysis (n=180 for Fulvestrant arm and n=172 for Anastrozole arm).

Posted

Median

Inter-Quartile Range

Months

Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
OG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

Secondary

Expected Duration of Clinical Benefit (EDoCB) for Fulvestrant Treatment Versus Anastrozole Treatment

EDoCB was estimated using the formula EDoCB = p Efp(x), where x = EDoCB, p = proportion of responders, and Efp(x) = mean duration of response for responders. The estimation was completed by using the maximum likelihood estimates of p and Efp(x), as described by Ellis (Ellis S et al. Analysis of duration of response in oncology trials, Contemp Clin Trials 2008; 29:456-65).

The ITT analysis set included all randomised patients.

Posted

Number

Days

Baseline RECIST 1.1 assessments (Day 0) and then every 12 weeks until disease progression or treatment discontinuation (up to approximately 38 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).
OG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).

Secondary

Comparison of the Effect of Fulvestrant Treatment Versus Anastrozole Treatment on Time to Deterioration of Health-Related Quality of Life (HRQoL)

The Functional Assessment of Cancer Therapy - Breast (FACT-B) questionnaire was the instrument selected to assess HRQoL and comprised of following subscales: physical well-being (PWB), functional well-being (FWB), social well-being, emotional well-being, and breast cancer subscale (BCS). The main outcome measure from the FACT-B questionnaire was the Trial Outcome Index (TOI), which was a summary of the following subscales: PWB, FWB, and BCS. Outcome measure is reported as median time to deterioration, defined as the interval from the date of baseline of final analysis to the first assessment of worsened without an improvement in the next 12 weeks in FACT-B TOI, or the date of death (by any cause in the absence of symptom deterioration). Time to deterioration as measured by FACT-B total score was derived similarly and is also reported.

The ITT analysis set included all randomised patients.

Posted

Median

Inter-Quartile Range

months

Quality of life questionnaires administered at 3 months post objective disease progression, then at 6-monthly intervals (approximately 75 months)

ID	Title	Description
OG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Fulvestrant 500 mg	Patients received fulvestrant (Faslodex™) 500 mg, administered as two 5 mL intramuscular injections, 1 in each buttock, at each visit on Days 0, 14 (±3), 28 (±3) and every 28 (±3) days thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive fulvestrant, also received placebo to match the anastrozole schedule (tablets, once daily).	157	230	39	228	125	228
EG001	Anastrozole 1 mg	Patients received anastrozole (Arimidex™), administered orally as a single tablet at a dose of 1 mg/day from randomisation on Day 0 and once daily thereafter. In order to support the double-blind, double-dummy design of the trial, each patient randomised to receive anastrozole also received placebo to match the fulvestrant schedule (injections on Days 0, 14 [±3], 28 [±3] and every 28 [±3] days thereafter).	159	232	36	232	127	232

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0016 events2 affected232 at risk
Anaemia macrocytic	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Atrial flutter	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Appendicitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Colorectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Bronchiectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Angina pectoris	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Jaundice cholestatic	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Bronchitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events2 affected232 at risk
Device related sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0012 events2 affected232 at risk
Gastroenteritis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected232 at risk
Peritonitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected228 at risk EG0010 events0 affected232 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected228 at risk EG0017 events4 affected232 at risk
Pyelonephritis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Septic shock	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected228 at risk EG0010 events0 affected232 at risk
Cardiac arrest	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Cardiac failure	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0013 events3 affected232 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected228 at risk EG0010 events0 affected232 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Traumatic spinal cord compression	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Hepatic enzyme increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events1 affected232 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events2 affected232 at risk
Acoustic neuroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0011 events1 affected232 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0013 events3 affected232 at risk
Palpitations	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Squamous cell carcinoma of the oral cavity	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Brain oedema	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Cerebral infarction	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected228 at risk EG0010 events0 affected232 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Anxiety	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events2 affected232 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected228 at risk EG0010 events0 affected232 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00010 events7 affected228 at risk EG0012 events2 affected232 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 events3 affected228 at risk EG0011 events1 affected232 at risk
Circulatory collapse	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0012 events2 affected232 at risk
Hypertensive crisis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected228 at risk EG0010 events0 affected232 at risk
Duodenal stenosis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected228 at risk EG0010 events0 affected232 at risk
Oesophageal dilatation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected228 at risk EG0011 events1 affected232 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected228 at risk EG0010 events0 affected232 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG00010 events9 affected228 at risk EG00121 events20 affected232 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00015 events12 affected228 at risk EG00112 events9 affected232 at risk
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG00035 events29 affected228 at risk EG00120 events18 affected232 at risk
Injection site pain	General disorders	MedDRA 25.0	Systematic Assessment	EG00015 events12 affected228 at risk EG00123 events10 affected232 at risk
Oedema peripheral	General disorders	MedDRA 25.0	Systematic Assessment	EG00011 events11 affected228 at risk EG00115 events14 affected232 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00018 events16 affected228 at risk EG0018 events8 affected232 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00013 events12 affected228 at risk EG0019 events9 affected232 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00065 events42 affected228 at risk EG00140 events31 affected232 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00025 events22 affected228 at risk EG00119 events18 affected232 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00019 events16 affected228 at risk EG00111 events8 affected232 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00022 events17 affected228 at risk EG00115 events11 affected232 at risk
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG00013 events12 affected228 at risk EG00112 events12 affected232 at risk
Anxiety	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG00013 events12 affected228 at risk EG0014 events4 affected232 at risk
Insomnia	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG00019 events18 affected228 at risk EG00116 events15 affected232 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00010 events10 affected228 at risk EG00117 events15 affected232 at risk
Hot flush	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG00035 events26 affected228 at risk EG00132 events24 affected232 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG00019 events18 affected228 at risk EG00125 events22 affected232 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00016 events16 affected228 at risk EG00113 events11 affected232 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00020 events15 affected228 at risk EG00117 events15 affected232 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00029 events25 affected228 at risk EG00127 events25 affected232 at risk

ID	Term
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D004958	Estradiol
D004963	Estrenes
D004962	Estranes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D045166	Estradiol Congeners
D012739	Gonadal Steroid Hormones
D042341	Gonadal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D009570	Nitriles
D009930	Organic Chemicals
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds