Tolvaptan Extension Study in Participants With ADPKD | NCT01214421

ID	Type	Description	Link
2010-018401-10	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Tolvaptan	Experimental	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 milligrams (mg) in the morning [AM]/15 mg in the evening [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily until the last participant originating from prior studies (either 156-04-251 or 156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290) who was eligible for efficacy analysis completed the Month 24.	Drug: Tolvaptan

Name	Type	Description	Arm Group Labels	Other Names
Tolvaptan	Drug	Tablets of 15 or 30 mg	Tolvaptan	OPC-41061

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)	Total kidney volume is a measure of disease progression in the ADPKD participants. Kidney volume was assessed in T1-weighted magnetic resonance images collected at each study site and sent to a central reviewing facility. At the central reviewing facility, radiologists used proprietary software to measure the volume of both kidneys in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). The percent change in the volume of both kidneys combined was analysed using mixed-effect model repeated measures (MMRM) analysis and reported. This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.	Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)

Secondary Outcomes

Measure	Description	Time Frame
Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)	Estimated Glomerular Filtration Rate (eGFR) according to CKD-EPI is calculated using the CKD-EPI equation, expressed as a single equation, is GFR = 141 × min (serum creatinine [Scr]/κ, 1)α × max(Scr/κ, 1)^-1.209 × 0.993 Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1 in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in eGFR for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). MMRM was used for the analysis. This outcome measure was analyzed only in the participants enrolled from the previous - 156-04-251, as pre-specified in the protocol.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

- Participants who had successfully completed a Phase 1, 2, or 3 tolvaptan ADPKD or renal impairment study, with a confirmed diagnosis of ADPKD from prior studies [either 156-04-251 (NCT00428948) or 156-04-250 (NCT00413777), 156-06-260, 156-09-284 (NCT01336972), 156-09-285 (NCT01210560), and 156-09-290 (NCT01451827)].

Exclusion Criteria:

Participants unable to provide written informed consent.
Participants (men or women) would not adhere to the reproductive precautions as outlined in the Informed Consent Form.
Participants (women only) with a positive urine pregnancy test.
Participants who were pregnant or breast-feeding.
Participants unable to take oral medications.
Participants who had allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine).
Participants with disorders in thirst recognition or an inability to access fluids.
Participants with critical electrolyte imbalances, as determined by the investigator
Participants with or at risk of significant hypovolemia, as determined by investigator.
Participants with significant anemia, as determined by investigator.
Participants with a history of substance abuse (within the last 3 years).
Participants who were taking other experimental (that is, non-marketed) therapies or were participating in another clinical drug or device study; participating in the off-drug follow-up period of another ADPKD trial with tolvaptan was permitted.
Participants unable to complete magnetic resonance imaging (MRI) assessments (for example, participants with ferro-magnetic prostheses, aneurysm clips, severe claustrophobia).
Participants who had taken a vasopressin antagonist (outside of previous participation in a tolvaptan study).
Participants unable to comply with anti-hypertensive or other important medical therapy.
Participants with advanced diabetes.
Participants who were taking medications or had an illness that could confound endpoint assessments (including taking approved therapies for the purpose of affecting polycystic kidney disease [PKD] cysts).

Name	Affiliation	Role
Study Director	Otsuka Pharmaceutical Development & Commercialization, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Otsuka Investigational Site		Mobile	Alabama	36617	United States
Otsuka Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37349694	Derived	Lioudis M, Zhou X, Davenport E, Nunna S, Krasa HB, Oberdhan D, Fernandes AW. Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis. BMC Nephrol. 2023 Jun 22;24(1):182. doi: 10.1186/s12882-023-03247-6.
37250503	Derived	Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Tolvaptan (From Study 156-04-251: Tolvaptan, Early Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 milligram (mg) in the morning [AM]/15 mg in the evening [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in previous Study 156-04-251, hence called as Early Treated.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Tolvaptan (From Study 156-04-251: Tolvaptan, Early Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in previous Study 156-04-251, hence called as Early Treated.
BG001	Tolvaptan (From Study 156-04-251: Placebo, Delayed Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in the previous Study 156-04-251, hence called as Delayed Treated.
BG002	Tolvaptan (From Other Studies: Tolvaptan, Early Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in other studies (156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290), hence called as Early Treated.
BG003	Tolvaptan (From Other Studies: Placebo, Delayed Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in other studies (156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290), hence called as Delayed Treated.
BG004	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
	BG00042.2± 6.9 BG00142.5± 7.2 BG00240.0± 10.1 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000254 BG001156 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00024 BG00119 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White/Caucasian

Title	Measurements
	BG000535 BG001302 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

Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)

Total kidney volume is a measure of disease progression in the ADPKD participants. Kidney volume was assessed in T1-weighted magnetic resonance images collected at each study site and sent to a central reviewing facility. At the central reviewing facility, radiologists used proprietary software to measure the volume of both kidneys in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). The percent change in the volume of both kidneys combined was analysed using mixed-effect model repeated measures (MMRM) analysis and reported. This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.

The Efficacy Sample consisted of all enrolled participants who took at least 1 dose of study drug and completed 3 years of study drug treatment in previous Study 156-04-251. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percent change

Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)

ID	Title	Description
OG000	Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in Study 156-04-251.
OG001	Tolvaptan, Delayed Treated (From Study 156-04-251: Placebo)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in Study 156-04-251.

Units	Counts
Participants	OG000505 OG001267

Title

Denominators

Categories

Title	Measurements
	OG00028.66± 26.14 OG00130.58± 27.21

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		Mixed Models Analysis		0.358		Ratio of geometric means (final values)	0.99			2-Sided	95	0.96	1.02					Superiority		Derived from the least squares (LS) mean difference between the treatment groups at each visit using MMRM model with factors of treatment, visit, region, baseline, baseline hypertensive status, baseline renal volume status, baseline creatinine clearance status, interaction of treatment and visit, and interaction of baseline and visit.

Secondary

Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)

Estimated Glomerular Filtration Rate (eGFR) according to CKD-EPI is calculated using the CKD-EPI equation, expressed as a single equation, is GFR = 141 × min (serum creatinine [Scr]/κ, 1)α × max(Scr/κ, 1)^-1.209 × 0.993 Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ or 1 in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in eGFR for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). MMRM was used for the analysis. This outcome measure was analyzed only in the participants enrolled from the previous - 156-04-251, as pre-specified in the protocol.

Posted

Least Squares Mean

Standard Deviation

mL/min/1.73 square meters (m^2)

Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)

ID	Title	Description
OG000	Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in Study 156-04-251.

Secondary

Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271

Annualized slope of TKV is a measure of renal function and disease progression in ADPKD participants. The annualized slope is calculated as percentage of growth in TKV (measured in mL by MRI) divided by each participant's years of participation for all participants was calculated using MMRM analysis in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing annualized slope of TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.

Posted

Number

percent change in TKV/participant-years

Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271)

ID	Title	Description
OG000	Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in Study 156-04-251.

Secondary

Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271

Annualized slope of eGFR (CKD-EPI) is a measure of renal function and disease progression in ADPKD participants. The annualized slope of eGFR (CKD-EPI) (divided by each participant's years of participation) for all participants was calculated using MMRM analysis in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). eGFR was calculated using the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula. This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.

Posted

Number

ml/min/1.73m^2/participant-years

Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271)

ID	Title	Description
OG000	Tolvaptan, Early Treated (From Study 156-04-251: Tolvaptan)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in Study 156-04-251.

Secondary

Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271

Annualized slope of TKV is a measure of renal function and disease progression in ADPKD participants. The annualized slope is calculated as percentage of growth in TKV (measured in mL by MRI) divided by each participant's years of participation, using MMRM analysis to compare annualized slope of TKV for the participants who received placebo in previous study (156-04-251) to annualized slope of TKV for the same participants who received tolvaptan in this study (156-08-271). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251 and who received placebo in the previous study, as pre-specified in the protocol.

Posted

Number

percent change in TKV/participant-years

Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251

ID	Title	Description
OG000	Tolvaptan, Delayed Treated (In Study 156-08-271)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in Study 156-04-251.

Secondary

Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271

Annualized slope of eGFR (CKD-EPI) is a measure of renal function and disease progression in ADPKD participants. The annualized slope of eGFR (calculated using CKD-EPI formula) divided by each participant's years of participation, using MMRM analysis to compare annualized slope of eGFR (CKD-EPI) for the participants who received placebo in previous study (156-04-251) to the annualized slope of eGFR (CKD-EPI) for the same participants who received tolvaptan in this study (156-08-271). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251 who received placebo in previous study and received tolvaptan in this study, as pre-specified in the protocol.

Posted

Number

ml/min/1.73m^2/participant-years

Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251

ID	Title	Description
OG000	Tolvaptan, Delayed Treated (In Study 156-08-271)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in Study 156-04-251.

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	Tolvaptan (From Study 156-04-251: Tolvaptan, Early Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in previous Study 156-04-251, hence called as Early Treated.	5	557	143	557	528	557
EG001	Tolvaptan (From Study 156-04-251: Placebo, Delayed Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in the previous Study 156-04-251, hence called as Delayed Treated.	0	314	79	314	310	314
EG002	Tolvaptan (From Other Studies: Tolvaptan, Early Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with tolvaptan in other studies (156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290), hence called as Early Treated.	0	181	34	181	175	181
EG003	Tolvaptan (From Other Studies: Placebo, Delayed Treated)	Participants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 mg [AM]/15 mg [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily up to Month 24. Participants were previously treated with placebo in other studies (156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290), hence called as Delayed Treated.	0	31	5	31	29	31

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0011 affected314 at risk EG0021 affected181 at risk EG0030 affected31 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Accelerated Idioventricular Rhythm	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Acute Coronary Syndrome	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Acute Myocardial Infarction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Angina Pectoris	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Atrial Fibrillation	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0012 affected314 at risk EG0020 affected181 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Cardiac Arrest	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Coronary Artery Disease	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Myocardial Infarction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Myocardial Ischaemia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Palpitations	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Pericarditis	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Prinzmetal Angina	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Sinus Arrhythmia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Congenital Cystic Kidney Disease	Congenital, familial and genetic disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Goitre	Endocrine disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Cataract	Eye disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Retinal Detachment	Eye disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Abdominal Hernia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0012 affected314 at risk EG0020 affected181 at risk EG003
Abdominal Pain	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0012 affected314 at risk EG0020 affected181 at risk EG003
Abdominal Pain Lower	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Gastritis Erosive	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Ileus Paralytic	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Inguinal Hernia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0005 affected557 at risk EG0013 affected314 at risk EG0020 affected181 at risk EG003
Intestinal Fistula	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Large Intestine Polyp	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Localised Intraabdominal Fluid Collection	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Pancreatitis Acute	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Pancreatitis Necrotising	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Umbilical Hernia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Peripheral Swelling	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Systemic Inflammatory Response Syndrome	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Bile Duct Stone	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Biliary Dyskinesia	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0012 affected314 at risk EG0020 affected181 at risk EG003
Cholecystitis Acute	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Drug-Induced Liver Injury	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0012 affected314 at risk EG0020 affected181 at risk EG003
Haemorrhagic Hepatic Cyst	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Hepatic Cyst	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0004 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Hepatic Failure	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Hepatic Pain	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Hepatocellular Injury	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Portal Hypertension	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Allergy to Arthropod Sting	Immune system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Atopy	Immune system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Drug Hypersensitivity	Immune system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Abdominal Abscess	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Appendicitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Bronchitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Bronchopulmonary Aspergillosis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Catheter Site Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Cervicitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Chronic Sinusitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Clostridium Difficile Colitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Clostridium Difficile Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Diarrhoea Infectious	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Diverticulitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0011 affected314 at risk EG0021 affected181 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Gastroenteritis Viral	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0022 affected181 at risk EG003
Genital Herpes	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Kidney Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Lobar Pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Mastitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Pharyngitis Streptococcal	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Pneumonia	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Pulmonary Tuberculosis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0006 affected557 at risk EG0011 affected314 at risk EG0022 affected181 at risk EG003
Renal Cyst Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0009 affected557 at risk EG0013 affected314 at risk EG0022 affected181 at risk EG003
Sepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0003 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Sinusitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Ureteritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0004 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Urosepsis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0021 affected181 at risk EG003
Viral Pericarditis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Wound Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Accidental Overdose	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Expired Product Administered	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Femur Fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Gun Shot Wound	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Incisional Hernia	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Joint Dislocation	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Ligament Rupture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Ligament Sprain	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Limb Injury	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Meniscus Injury	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Renal Haematoma	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Shunt Occlusion	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Tendon Rupture	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Alanine Aminotransferase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0013 affected314 at risk EG0025 affected181 at risk EG003
Aspartate Aminotransferase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0023 affected181 at risk EG003
Blood Alkaline Phosphatase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Blood Bilirubin Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Blood Creatine Phosphokinase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Blood Creatinine Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0006 affected557 at risk EG0016 affected314 at risk EG0021 affected181 at risk EG003
Blood Lactate Dehydrogenase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Gamma-Glutamyltransferase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0013 affected314 at risk EG0020 affected181 at risk EG003
Glomerular Filtration Rate Decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Haemoglobin Decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Hepatic Enzyme Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Liver Function Test Abnormal	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0012 affected314 at risk EG0020 affected181 at risk EG003
Smear Cervix Abnormal	Investigations	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Transaminases Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0003 affected557 at risk EG0012 affected314 at risk EG0022 affected181 at risk EG003
Vasopressin Challenge Test Abnormal	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
White Blood Cell Count Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Chondropathy	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Flank Pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Foot Deformity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Intervertebral Disc Protrusion	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Loose Body In Joint	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Basal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Breast Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Cervix Cancer Metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Cholesterin Granuloma Of Middle Ear	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Endometrial Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Gastrointestinal Stromal Tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Intraductal Proliferative Breast Lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Malignant Melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Plasma Cell Myeloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Testis Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Uterine Leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Amnesia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Ataxia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Carotid Artery Aneurysm	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Carotid Artery Dissection	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Cerebral Atrophy	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Cerebrovascular Accident	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0013 affected314 at risk EG0020 affected181 at risk EG003
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Essential Tremor	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Intracranial Aneurysm	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected557 at risk EG0013 affected314 at risk EG0021 affected181 at risk EG003
Ischaemic Stroke	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Lumbar Radiculopathy	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Occipital Neuralgia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Polyneuropathy	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Subarachnoid Haemorrhage	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Transient Ischaemic Attack	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Ectopic Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Gestational Hypertension	Pregnancy, puerperium and perinatal conditions	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Depression	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Major Depression	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Suicide Attempt	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Acute Kidney Injury	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0013 affected314 at risk EG0021 affected181 at risk EG003
Calculus Ureteric	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Calculus Urinary	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Chronic Kidney Disease	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0005 affected557 at risk EG0012 affected314 at risk EG0022 affected181 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Nephropathy	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Renal Cyst	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Renal Cyst Haemorrhage	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0006 affected557 at risk EG0014 affected314 at risk EG0022 affected181 at risk EG003
Renal Cyst Ruptured	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Renal Failure	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Renal Haemorrhage	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Renal Impairment	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0006 affected557 at risk EG0013 affected314 at risk EG0021 affected181 at risk EG003
Renal Pain	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0012 affected314 at risk EG0020 affected181 at risk EG003
Urinary Incontinence	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Urine Flow Decreased	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Breast Discomfort	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Breast Haematoma	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Endometriosis	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Menorrhagia	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Postmenopausal Haemorrhage	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Acute Lung Injury	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Nasal Septum Deviation	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Pharyngeal Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0022 affected181 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0002 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Hidradenitis	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Aneurysm	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Aortic Dissection	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Arterial Stenosis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003
Deep Vein Thrombosis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0010 affected314 at risk EG0021 affected181 at risk EG003
Hypertension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Peripheral Arterial Occlusive Disease	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Peripheral Venous Disease	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 affected557 at risk EG0011 affected314 at risk EG0020 affected181 at risk EG003
Subclavian Vein Thrombosis	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 affected557 at risk EG0010 affected314 at risk EG0020 affected181 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG00035 affected557 at risk EG00120 affected314 at risk EG00213 affected181 at risk EG0030 affected31 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00037 affected557 at risk EG00115 affected314 at risk EG00213 affected181 at risk EG003
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00023 affected557 at risk EG00116 affected314 at risk EG0024 affected181 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00023 affected557 at risk EG00125 affected314 at risk EG0028 affected181 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00060 affected557 at risk EG00130 affected314 at risk EG00213 affected181 at risk EG003
Dry Mouth	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00045 affected557 at risk EG00144 affected314 at risk EG00225 affected181 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00029 affected557 at risk EG00115 affected314 at risk EG0028 affected181 at risk EG003
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00024 affected557 at risk EG00111 affected314 at risk EG00210 affected181 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00042 affected557 at risk EG00132 affected314 at risk EG00222 affected181 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG00032 affected557 at risk EG00115 affected314 at risk EG0029 affected181 at risk EG003
Fatigue	General disorders	MedDRA (18.0)	Systematic Assessment	EG00053 affected557 at risk EG00154 affected314 at risk EG00232 affected181 at risk EG003
Oedema Peripheral	General disorders	MedDRA (18.0)	Systematic Assessment	EG00051 affected557 at risk EG00132 affected314 at risk EG0029 affected181 at risk EG003
Thirst	General disorders	MedDRA (18.0)	Systematic Assessment	EG000261 affected557 at risk EG001161 affected314 at risk EG00280 affected181 at risk EG003
Bronchitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00030 affected557 at risk EG00117 affected314 at risk EG0024 affected181 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00031 affected557 at risk EG00120 affected314 at risk EG0029 affected181 at risk EG003
Gastroenteritis Viral	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00012 affected557 at risk EG0017 affected314 at risk EG0026 affected181 at risk EG003
Influenza	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00042 affected557 at risk EG00125 affected314 at risk EG00218 affected181 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00083 affected557 at risk EG00155 affected314 at risk EG00218 affected181 at risk EG003
Sinusitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00040 affected557 at risk EG00119 affected314 at risk EG00213 affected181 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00061 affected557 at risk EG00135 affected314 at risk EG00228 affected181 at risk EG003
Urinary Tract Infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG00061 affected557 at risk EG00133 affected314 at risk EG00216 affected181 at risk EG003
Aspartate Aminotransferase Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00019 affected557 at risk EG0015 affected314 at risk EG0027 affected181 at risk EG003
Blood Creatinine Increased	Investigations	MedDRA (18.0)	Systematic Assessment	EG00096 affected557 at risk EG00139 affected314 at risk EG00220 affected181 at risk EG003
Decreased Appetitie	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0005 affected557 at risk EG00113 affected314 at risk EG00212 affected181 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00035 affected557 at risk EG0019 affected314 at risk EG0026 affected181 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00037 affected557 at risk EG00115 affected314 at risk EG0022 affected181 at risk EG003
Polydipsia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00062 affected557 at risk EG00151 affected314 at risk EG00238 affected181 at risk EG003
Vitamin D Deficiency	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG00034 affected557 at risk EG00116 affected314 at risk EG00213 affected181 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00057 affected557 at risk EG00116 affected314 at risk EG00213 affected181 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00060 affected557 at risk EG00140 affected314 at risk EG00215 affected181 at risk EG003
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00028 affected557 at risk EG00118 affected314 at risk EG0025 affected181 at risk EG003
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG00038 affected557 at risk EG00111 affected314 at risk EG0027 affected181 at risk EG003
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00030 affected557 at risk EG00136 affected314 at risk EG00213 affected181 at risk EG003
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG00075 affected557 at risk EG00156 affected314 at risk EG00220 affected181 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG00047 affected557 at risk EG00136 affected314 at risk EG00213 affected181 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG000145 affected557 at risk EG001111 affected314 at risk EG00294 affected181 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG00030 affected557 at risk EG00124 affected314 at risk EG00220 affected181 at risk EG003
Polyuria	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG000231 affected557 at risk EG001175 affected314 at risk EG002111 affected181 at risk EG003
Renal Cyst Ruptured	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG0003 affected557 at risk EG0012 affected314 at risk EG0022 affected181 at risk EG003
Renal Pain	Renal and urinary disorders	MedDRA (18.0)	Systematic Assessment	EG000147 affected557 at risk EG00190 affected314 at risk EG00243 affected181 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG00042 affected557 at risk EG00123 affected314 at risk EG00210 affected181 at risk EG003
Dry Skin	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0007 affected557 at risk EG00112 affected314 at risk EG0027 affected181 at risk EG003
Hypertension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG000160 affected557 at risk EG00182 affected314 at risk EG00242 affected181 at risk EG003

Certain Agreements

ID	Term
D016891	Polycystic Kidney, Autosomal Dominant
D007674	Kidney Diseases

ID	Term
D007690	Polycystic Kidney Diseases
D052177	Kidney Diseases, Cystic
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D000015	Abnormalities, Multiple
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D000072661	Ciliopathies
D030342	Genetic Diseases, Inborn

ID	Term
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds