Evaluation of Efficacy, Safety of Vandetanib in Patients... | NCT01876784

ID	Type	Description	Link
2013-000422-58	EudraCT Number
LPS14813	Other Identifier	Sanofi

Label	Type	Description	Intervention Names
Vandetanib/ Vandetanib	Experimental	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.	Drug: Vandetanib (SAR390530)
Placebo/ Vandetanib	Placebo Comparator	Participants received placebo matched to Vandetanib tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, and experienced disease progression were offered the option of treatment in open-label period with vandetanib, if in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to begin open-label vandetanib treatment i.e., 300 mg tablet, orally once daily for up to 31 months.	Drug: Vandetanib (SAR390530) Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Vandetanib (SAR390530)	Drug	Pharmaceutical form: tablet Route of administration: oral	Placebo/ Vandetanib Vandetanib/ Vandetanib

Measure	Description	Time Frame
Progression-Free Survival (PFS)	The PFS was defined as the time (in months) from randomization until the date of first documented disease progression or death (from any cause), whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) was defined as: at least a 20% increase and absolute increase of 5 mm in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Analysis was performed by Kaplan-Meier method.	Randomization until disease progression or death, assessed every 12 weeks (up to 22 months)

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from the date of randomization until death due to any cause. In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.	From randomization to the date of death due to any cause (maximum duration: up to 42 months)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provision of informed consent to participate in the study as well as provision of informed consent to provide a sample of a previously obtained archival tumor biopsy.
Female or male aged 18 years and older with previously confirmed histological diagnosis of locally advanced or metastatic differentiated (excluding minimally invasive follicular) thyroid cancer not amenable to surgical resection, external beam radiotherapy or local therapy.
Measurable disease defined as at least one lesion, not irradiated within 12 weeks of the date of randomization, that can be accurately measured at baseline.
Participants must have experienced progression within 14 months and be RAI-refractory/resistant or unsuitable for RAI.
Thyroid-stimulating hormone (TSH) suppression below 0.5 mU/L is required.
World Health Organization (WHO) or Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
Negative pregnancy test (urine or serum) for female participants of childbearing potential.

Exclusion Criteria:

Inadequate organ function as defined by: (1) Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) greater than 2.5*upper limit of normal (ULN), or greater than 5.0*ULN if judged by the Investigator to be related to liver metastases. (2) Serum bilirubin greater than 1.5*ULN. This criterion does not apply to participants with known Gilbert's Disease. (3) Creatinine clearance <50 mL/min (calculated by Cockcroft-Gault formula).
Risk of prolonged interval between Q and T (QT) on an electrocardiogram (ECG) corrected for heart rate (QTc) as defined by: (1) Current therapy with any medication known to be associated with Torsades de pointes or potent inducers of cytochrome CYP3A4. (2) History of QT prolongation. (3) Congenital long QT syndrome. (4) QT interval corrected for heart rate by the Bazett's method (QTcB) correction unmeasurable or greater than 480 ms on screening ECG.
Previous therapy with approved or investigational tyrosine kinase or anti- vascular endothelial growth factor (VEGF) receptor inhibitors or targeted therapies (e.g. multi-targeted kinase inhibitors such as sorafenib, AMG-706, sunitinib, pazopanib, lenvatinib).
RAI therapy within 12 weeks prior to first dose of study drug, and radiation therapy other than RAI, including external beam, if not completed prior to randomization.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Little Rock	Arkansas	72205	United States
Research Site

ID	Title	Description
FG000	Vandetanib/Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if, in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.

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

Progression-Free Survival (PFS)

The PFS was defined as the time (in months) from randomization until the date of first documented disease progression or death (from any cause), whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) was defined as: at least a 20% increase and absolute increase of 5 mm in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Analysis was performed by Kaplan-Meier method.

Intent to treat population included all randomized participants.

Posted

Median

95% Confidence Interval

months

Randomization until disease progression or death, assessed every 12 weeks (up to 22 months)

ID	Title	Description
OG000	Randomized Treatment Period: Vandetanib	Vandetanib 300 mg tablet, orally once daily until disease progression or death.
OG001	Randomized Treatment Period: Placebo	Placebo matched to vandetanib tablet, orally once daily until disease progression or death.

Units	Counts
Participants	OG000119 OG001119

Title

Denominators

Categories

Title	Measurements
	OG00010.0(6.0 to 11.1) OG0015.7(5.5 to 8.4)

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	A multiple testing procedure (MTP) with an alpha-exhaustive recycling strategy was employed to provide adequate control of type I error.	Log Rank		0.080	Threshold for significance at 0.05 level.	Hazard Ratio (HR)	0.75			2-Sided	95	0.55	1.03			Vandetanib 300 mg vs Placebo		Superiority or Other (legacy)

Secondary

Overall Survival (OS)

OS was defined as the time from the date of randomization until death due to any cause. In the absence of observation of death, survival time was censored to last date the participant is known to be alive or at the cut-off date, whichever comes first. Analysis was performed by Kaplan-Meier method.

Analysis was performed on intent-to-treat population.

Posted

Median

95% Confidence Interval

months

From randomization to the date of death due to any cause (maximum duration: up to 42 months)

ID	Title	Description
OG000	Vandetanib/Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if, in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.
OG001	Placebo/Vandetanib	Participants received placebo matched to Vandetanib tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, and experienced disease progression were offered the option of treatment in open-label period with vandetanib, if in the investigator's opinion, such treatment was of clinical benefit to the participant, and if the participant agreed and provided their informed consent to begin open-label vandetanib treatment i.e., 300 mg tablet, orally once daily for up to 31 months.

Secondary

Randomized Treatment Period: Percent Change From Baseline in Tumor Size (TS) at Week 36

Tumor size was the sum of the longest diameters of the target lesions. Target lesions were measurable tumor lesions. Baseline was defined as the last evaluable assessment prior to starting treatment.

Analysis was performed on intent-to-treat population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 36

ID	Title	Description
OG000	Randomized Treatment Period: Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months).
OG001	Randomized Treatment Period: Placebo	Participants received placebo matched to Vandetanib tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months).

Units	Counts
Participants

Secondary

Percentage of Participants With Objective Response

Objective Response was defined as the percentage (%) of participants with complete response or partial response. Per RECIST 1.1 criteria, complete response was defined as the disappearance of all target lesions since Baseline. Any pathological lymph nodes selected as target lesions must have a reduction in short axis to less than (<)10 millimeters (mm). Partial response was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the Baseline sum of diameters. Progressive Disease was defined as at least at least a 20% increase and absolute increase of 5 mm in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Analysis was performed on intent-to-treat population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Number

percentage of participants

From randomization to the date of first documented tumor progression, or death due to any cause, whichever comes first (maximum duration: up to 42 months)

ID	Title	Description
OG000	Vandetanib/Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if, in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.

Secondary

Time to Worsening of Pain (TWP) Using Numeric Rating Scale (NRS) of Worst Pain

Time to worsening of pain was defined as the time interval from the date of randomization to the date of first assessment of worsening of pain with no evidence of improvement within the next 14 days. Participants rate their worst pain intensity during the past seven days using an 11-point NRS scale, where 0 represents "no pain" and 10 represents "pain as bad as you can imagine." Higher scores indicated greater pain severity. TWP analysis was performed using Kaplan-Meier method.

Analysis was performed on intent-to-treat population.

Posted

Median

95% Confidence Interval

months

From randomization to the date of first assessment of worsening of pain (maximum duration: up to 42 months)

ID	Title	Description
OG000	Vandetanib/Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if, in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.
OG001	Placebo/Vandetanib	Participants received placebo matched to Vandetanib tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, and experienced disease progression were offered the option of treatment in open-label period with vandetanib, if in the investigator's opinion, such treatment was of clinical benefit to the participant, and if the participant agreed and provided their informed consent to begin open-label vandetanib treatment i.e., 300 mg tablet, orally once daily for up to 31 months.

Secondary

Duration of Response (DOR)

Duration of response was defined as the time from the date of first documented response until the date of documented progression or death. If participants did not progress following a response, then their DOR used the PFS censoring time. Per RECIST 1.1, progressive disease was defined as at least a 20% increase and absolute increase of 5 mm in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. DOR analysis was performed using Kaplan-Meier method.

Analysis was performed on subset of participants with response. Here, '0' in 'overall number of participants' analyzed signifies that no participant in the Placebo/Vandetanib achieved any response, therefore DOR was not analyzed.

Posted

Median

95% Confidence Interval

months

From the date of first response to the date of first documented tumor progression or death due to any cause whichever comes first (maximum duration: up to 42 months)

ID	Title	Description
OG000	Vandetanib/Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if, in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.
OG001

Secondary

Randomized Treatment Period: PK Parameters: Maximum Plasma Concentration (Cmax)

Number of participants analyzed= participants with available data for the time points.

Posted

Mean

Standard Deviation

ng/ml

Post-dose on Week 1 to Week 48

ID	Title	Description
OG000	Randomized Treatment Period: Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months).

Units	Counts
Participants	OG00098

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG0030 events0 affected74 at risk
Bone Marrow Failure	Blood and lymphatic system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0012 events2 affected118 at risk EG0020 events0 affected23 at risk EG003
Acute Myocardial Infarction	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Atrial Fibrillation	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0012 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Atrial Flutter	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Atrioventricular Block	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Cardiac Arrest	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Cardiac Failure	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Cardiac Failure Acute	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Ventricular Extrasystoles	Cardiac disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Inappropriate Antidiuretic Hormone Secretion	Endocrine disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0003 events3 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0012 events2 affected118 at risk EG0020 events0 affected23 at risk EG003
Inguinal Hernia	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Large Intestine Polyp	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pneumoperitoneum	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Disease Progression	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Impaired Healing	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Multiple Organ Dysfunction Syndrome	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pyrexia	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Bronchitis	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Lung Abscess	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Lung Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events2 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pneumonia	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0004 events4 affected117 at risk EG0012 events2 affected118 at risk EG0021 events1 affected23 at risk EG003
Post Procedural Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Respiratory Tract Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Sepsis	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Skin Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Viral Upper Respiratory Tract Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Femur Fracture	Injury, poisoning and procedural complications	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Hip Fracture	Injury, poisoning and procedural complications	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Hypobarism	Injury, poisoning and procedural complications	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Post Procedural Haemorrhage	Injury, poisoning and procedural complications	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Rib Fracture	Injury, poisoning and procedural complications	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Blood Creatinine Increased	Investigations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Troponin Increased	Investigations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pathological Fracture	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Adenocarcinoma Gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Bladder Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Colon Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Gastric Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Malignant Neoplasm Progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Metastases To Spinal Cord	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Squamous Cell Carcinoma Of Lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Tumour Haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Epilepsy	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Generalised Tonic-Clonic Seizure	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0002 events2 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Ivth Nerve Paresis	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Ischaemic Stroke	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0002 events2 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Seizure	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Somnolence	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Vertebrobasilar Insufficiency	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Depression	Psychiatric disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0012 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Acute Kidney Injury	Renal and urinary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Cystitis Noninfective	Renal and urinary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Nephrotic Syndrome	Renal and urinary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Urinary Tract Obstruction	Renal and urinary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Benign Prostatic Hyperplasia	Reproductive system and breast disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0013 events3 affected118 at risk EG0020 events0 affected23 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0002 events1 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0004 events2 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Dermatitis Bullous	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Henoch-Schonlein Purpura	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Photosensitivity Reaction	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Stevens-Johnson Syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Varicose Vein	Vascular disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events6 affected117 at risk EG0018 events6 affected118 at risk EG0021 events1 affected23 at risk EG0030 events0 affected74 at risk
Cornea Verticillata	Eye disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0009 events9 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0009 events8 affected117 at risk EG0019 events8 affected118 at risk EG0020 events0 affected23 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0009 events6 affected117 at risk EG0014 events4 affected118 at risk EG0021 events1 affected23 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00011 events9 affected117 at risk EG00113 events11 affected118 at risk EG0022 events2 affected23 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG000126 events77 affected117 at risk EG00129 events24 affected118 at risk EG0025 events3 affected23 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0006 events6 affected117 at risk EG0012 events2 affected118 at risk EG0021 events1 affected23 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events6 affected117 at risk EG0014 events3 affected118 at risk EG0020 events0 affected23 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00024 events22 affected117 at risk EG00121 events17 affected118 at risk EG0021 events1 affected23 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0006 events6 affected117 at risk EG0013 events3 affected118 at risk EG0020 events0 affected23 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00014 events9 affected117 at risk EG00115 events12 affected118 at risk EG0021 events1 affected23 at risk EG003
Asthenia	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00027 events21 affected117 at risk EG00115 events15 affected118 at risk EG0021 events1 affected23 at risk EG003
Fatigue	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00014 events13 affected117 at risk EG00113 events13 affected118 at risk EG0021 events1 affected23 at risk EG003
Non-Cardiac Chest Pain	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0003 events3 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pyrexia	General disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events6 affected117 at risk EG00114 events10 affected118 at risk EG0020 events0 affected23 at risk EG003
Hepatic Function Abnormal	Hepatobiliary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events6 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0001 events1 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00010 events8 affected117 at risk EG0019 events7 affected118 at risk EG0020 events0 affected23 at risk EG003
Paronychia	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0003 events3 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0005 events5 affected117 at risk EG0018 events7 affected118 at risk EG0020 events0 affected23 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00016 events11 affected117 at risk EG0014 events3 affected118 at risk EG0020 events0 affected23 at risk EG003
Alanine Aminotransferase Increased	Investigations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00023 events16 affected117 at risk EG0016 events4 affected118 at risk EG0020 events0 affected23 at risk EG003
Aspartate Aminotransferase Increased	Investigations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00021 events15 affected117 at risk EG0017 events4 affected118 at risk EG0020 events0 affected23 at risk EG003
Blood Creatinine Increased	Investigations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0009 events7 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Electrocardiogram Qt Prolonged	Investigations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00055 events36 affected117 at risk EG0016 events4 affected118 at risk EG0021 events1 affected23 at risk EG003
Weight Decreased	Investigations	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00011 events10 affected117 at risk EG0014 events3 affected118 at risk EG0020 events0 affected23 at risk EG003
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00023 events21 affected117 at risk EG0012 events2 affected118 at risk EG0021 events1 affected23 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00018 events17 affected117 at risk EG0013 events3 affected118 at risk EG0021 events1 affected23 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00011 events9 affected117 at risk EG0015 events5 affected118 at risk EG0020 events0 affected23 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00019 events9 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00011 events7 affected117 at risk EG0015 events5 affected118 at risk EG0020 events0 affected23 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0009 events8 affected117 at risk EG00114 events12 affected118 at risk EG0022 events2 affected23 at risk EG003
Musculoskeletal Chest Pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00010 events8 affected117 at risk EG0019 events9 affected118 at risk EG0020 events0 affected23 at risk EG003
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0000 events0 affected117 at risk EG00111 events10 affected118 at risk EG0020 events0 affected23 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00023 events16 affected117 at risk EG00111 events9 affected118 at risk EG0020 events0 affected23 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0006 events6 affected117 at risk EG0015 events5 affected118 at risk EG0020 events0 affected23 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00015 events15 affected117 at risk EG0012 events2 affected118 at risk EG0020 events0 affected23 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events7 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0008 events8 affected117 at risk EG0010 events0 affected118 at risk EG0021 events1 affected23 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00011 events11 affected117 at risk EG00116 events12 affected118 at risk EG0021 events1 affected23 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0003 events3 affected117 at risk EG0014 events4 affected118 at risk EG0020 events0 affected23 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events7 affected117 at risk EG00110 events10 affected118 at risk EG0020 events0 affected23 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0005 events4 affected117 at risk EG0019 events8 affected118 at risk EG0020 events0 affected23 at risk EG003
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0003 events3 affected117 at risk EG0017 events6 affected118 at risk EG0020 events0 affected23 at risk EG003
Acne	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0009 events9 affected117 at risk EG0012 events2 affected118 at risk EG0020 events0 affected23 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0006 events6 affected117 at risk EG0013 events2 affected118 at risk EG0020 events0 affected23 at risk EG003
Dermatitis Acneiform	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00014 events13 affected117 at risk EG0012 events2 affected118 at risk EG0020 events0 affected23 at risk EG003
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00018 events18 affected117 at risk EG0016 events6 affected118 at risk EG0020 events0 affected23 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events5 affected117 at risk EG0012 events2 affected118 at risk EG0020 events0 affected23 at risk EG003
Palmar-Plantar Erythrodysaesthesia Syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events6 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Photosensitivity Reaction	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00015 events14 affected117 at risk EG0010 events0 affected118 at risk EG0020 events0 affected23 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0006 events6 affected117 at risk EG0015 events5 affected118 at risk EG0021 events1 affected23 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00051 events36 affected117 at risk EG0017 events6 affected118 at risk EG0020 events0 affected23 at risk EG003
Rash Maculo-Papular	Skin and subcutaneous tissue disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG0007 events7 affected117 at risk EG0011 events1 affected118 at risk EG0020 events0 affected23 at risk EG003
Hypertension	Vascular disorders	MedDRA 19.1 - 25 .1	Systematic Assessment	EG00053 events48 affected117 at risk EG0019 events9 affected118 at risk EG0020 events0 affected23 at risk EG003

ID	Title	Description
BG000	Vandetanib/Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if, in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.
BG001	Placebo/Vandetanib	Participants received placebo matched to Vandetanib tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, and experienced disease progression were offered the option of treatment in open-label period with vandetanib, if in the investigator's opinion, such treatment was of clinical benefit to the participant, and if the participant agreed and provided their informed consent to begin open-label vandetanib treatment i.e., 300 mg tablet, orally once daily for up to 31 months.
BG002	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Randomized Treatment Period: Vandetanib	Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months).	37	117	111	117
EG001	Randomized Treatment Period: Placebo	Participants received placebo matched to Vandetanib tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months).	19	118	87	118
EG002	Open-Label Treatment Period: Vandetanib/Vandetanib	Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.	7	23	9	23
EG003	Open-Label Treatment Period: Placebo/Vandetanib	Participants who completed the randomized treatment period, and experienced disease progression were offered the option of treatment in open-label period with vandetanib, if, in the investigator's opinion, such treatment was of clinical benefit to the participant, and if the participant agreed and provided their informed consent to begin open-label vandetanib treatment i.e., 300 mg tablet, orally once daily for up to 31 months.	24	74	62	74