A Study to Test the Effect of Different Doses of Avencigu... | NCT04736628

NCT04736628

ID	Type	Description	Link
2020-002930-33	EudraCT Number

Status Module

Description Module

Label	Type	Description	Intervention Names
Avenciguat 1 mg TID	Experimental	TID=ter in die (3 times a day)	Drug: Avenciguat
Avenciguat 2 mg TID	Experimental		Drug: Avenciguat
Avenciguat 3 mg TID	Experimental		Drug: Avenciguat
Placebo	Placebo Comparator		Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Avenciguat	Drug	Avenciguat	Avenciguat 1 mg TID Avenciguat 2 mg TID Avenciguat 3 mg TID

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment	Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in 10-hour urine after 20 weeks of trial treatment is reported. Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12, and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient. Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20). The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.	The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2, Week -1, Week 0 pre-dose) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment	Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment is reported. Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12 and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient. The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day. Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20). The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
Male or female patients aged ≥18 years at time of consent.
Estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) ≥ 20 and < 90 mL/min/1.73 m2 at Visit 1 by central laboratory analysis. eGFR must remain ≥20 mL/min/1.73 m2 after Visit 1 up to the start of Visit 3, measured by central or any local laboratory analysis.
Urine albumin creatinine ratio (UACR) ≥ 200 and < 3,500 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1.
Patients with macroalbuminuria (>300 mg/g) should be treated with the highest tolerated dose of either Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both). For patients with microalbuminuria the use of ACEi or ARB is at the discretion of the Investigator. Treatment should be at a stable dose for ≥ 4 weeks before Visit 1 with no planned change of the therapy during the trial.
If the patient is taking any of the following medications they should be on a stable dose at least 4 weeks prior to visit 1 until start of treatment, with no planned change of the therapy during the trial: anti-hypertensives, non-steroidal anti-inflammatory drugs (NSAIDs), endothelin receptor antagonists, systemic steroids or Sodium-glucose co-transporter-2 (SGLT2) inhibitors.
In the Investigator's judgment any kind of diagnosed chronic kidney disease whose primary cause is clinically not considered to be of diabetic origin.

Further inclusion criteria apply

Exclusion Criteria:

Treatment with Renin Angiotensin Aldosterone System (RAAS) interventions (apart from either ACEi or ARB), Phosphodiesterase-5-inhibitors, non-specific phosphodiesterase inhibitors (such as dipyridamole and theophylline), Nitric Oxide (NO) donors including nitrates, soluble Guanylate Cyclase (sGC)-stimulators/activators (other than trial treatment) or any other restricted medication (including Organic Anion-Transporting Polypeptide 1B1 and 1B3 (OATP1B1/3) inhibitors, Uridine 5'-diphosphate -glucuronosyltransferase (UGT) inhibitors/inducers) as provided in the Investigator Site File (ISF) within 4 weeks prior to visit 1 and throughout screening and baseline run-in. Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
Any clinically relevant laboratory value from screening until start of trial treatment which, in the investigator's judgement, puts the patient at additional risk.
Diagnosed with diabetic kidney disease.
Any immunosuppression therapy or immunotherapy in last 3 months prior to visit 1 and throughout screening and baseline run-in (except prednisolone ≤10 mg or equivalent).
Acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition in the 30 days prior to Visit 1 until the start of trial treatment.
Planned start of chronic renal replacement therapy during the trial or end stage renal disease before start of trial treatment.
Known history of moderate or severe symptomatic orthostatic dysregulation as judged by the investigator before start of trial treatment.
The patient has an active infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (or is known to have a positive test from screening until randomisation).
Further exclusion criteria apply

Facility	Status	City	State	ZIP	Country	Contacts
Clearview Medical Research, LLC		Canyon Country	California	91351	United States
Rancho Cucamonga Clinical Trials

PubMed Identifier	Type	Citation	Retractions
38795055	Derived	Heerspink HJL, Cherney D, Gafor AHA, Gorriz JL, Pergola PE, Tang SCW, Desch M, Iliev H, Sun Z, Steubl D, Nangaku M. Effect of Avenciguat on Albuminuria in Patients with CKD: Two Randomized Placebo-Controlled Trials. J Am Soc Nephrol. 2024 Sep 1;35(9):1227-1239. doi: 10.1681/ASN.0000000000000418. Epub 2024 May 25.

Label	URL
Related Info	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Avenciguat 1 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 15, 2022	Jul 30, 2024

Arm/Group Information

ID	Title	Description
BG000	Avenciguat 1 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
BG001	Avenciguat 2 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
BG002	Avenciguat 3 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
BG003	Placebo	This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
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
	BG00054.6± 16.3 BG00160.4± 15.5 BG00259.3± 15.0 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00021 BG00116 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00018 BG00120 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0003 BG0014 BG002

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) use at randomization

Number of patients in each category sodium-glucose cotransporter 2 inhibitor (SGLT2i) use at randomization. The reported categories of SGLT2i use at randomization are: Yes; No.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG00017 BG001

Baseline urine albumine creatinine ratio (UACR), 10-hour urine

Baseline UACR measured in 10-hour urine is reported. UACR is a ratio between two measured substances i.e., albumine and creatinine and it is calculated as: (Urine albumin (milligram (mg)/deciliter (dL)))/(urine creatinine gram (g)/deciliter (dL))= UACR in mg/g. Albuminuria is present when UACR is greater than 30 mg/g and is a marker for chronic kidney disease (CKD). Baseline was defined as the mean of all non-missing assessments from visit 2 (Week -2) until prior to the first intake of trial medication.

Mean

Standard Deviation

milligram/gram

Title

Denominators

Categories

Title	Measurements
	BG0001024.1± 920.1 BG001

Baseline Urine Albumine Creatinine Ratio (UACR) in First Morning Void (FMV)

UACR measured in FMV is reported. UACR is a ratio between two measured substances i.e., albumine and creatinine and it is calculated as: (urine albumin (milligram (mg)/deciliter (dL)))/(urine creatinine gram (g)/deciliter (dL))= UACR in mg/g. Albuminuria is present when UACR is greater than 30 mg/g and is a marker for chronic kidney disease (CKD). Baseline was defined as the mean of all non-missing assessments from visit 2 (Week -2) until prior to the first intake of trial medication.

Mean

Standard Deviation

milligram/gram

Title

Denominators

Categories

Title	Measurements
	BG000879.1± 840.8 BG001

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

Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment

Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in 10-hour urine after 20 weeks of trial treatment is reported.

Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12, and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient.

Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20).

The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.

Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Posted

Least Squares Mean

Standard Error

log (mg/g)

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2, Week -1, Week 0 pre-dose) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.

ID	Title	Description
OG000	Avenciguat 1 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
OG001	Avenciguat 2 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
OG002	Avenciguat 3 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
OG003	Placebo	This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.

Units	Counts
Participants	OG00064 OG00161 OG00262 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.210± 0.067 OG001-0.190± 0.068 OG002-0.217± 0.068 OG003

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 OG003	Least Squares Mean differences and 95% confidence intervals were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12 and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient.	Mixed-effect Model repeat Measurement		0.0179		Mean Difference (Net)	-0.228			2-Sided	95	-0.417	-0.040			Least Squares Mean of "Avenciguat 1 mg TID" - Least Squares Mean of "Placebo".		Other

Secondary

Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment

Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment is reported.

Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12 and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient.

The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day. Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20). The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.

Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Posted

Least Squares Mean

Standard Error

log (mg/g)

The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2 and Week -1) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.

ID	Title	Description
OG000	Avenciguat 1 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.

Secondary

Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment

Number of patients achieving urine albumin creatinine ratio (UACR) decreases in 10-hour urine of at least 20% from baseline after 20 weeks of trial treatment.

During the 10-hour period every time the patient urinates, and the patient collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample.

Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Posted

Count of Participants

Participants

At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment.

ID	Title	Description
OG000	Avenciguat 1 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
OG001	Avenciguat 2 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.

Secondary

Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment

Number of patients achieving urine albumin creatinine ratio (UACR) decreases in First Morning Void urine of at least 20% from baseline after 20 weeks of trial treatment is reported. The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day.

Full Analysis Set (FAS): included all patients who had at least one baseline measurement of UACR in Week -2, -1, or 0 and at least 1 post-baseline measurement after Week 6.

Posted

Count of Participants

Participants

At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment.

ID	Title	Description
OG000	Avenciguat 1 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.
OG001	Avenciguat 2 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Avenciguat 1 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Weeks 1 to 20 (included). Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	64	3	64	17	64
EG001	Avenciguat 2 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg of avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 20 of treatment. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	65	3	65	19	65
EG002	Avenciguat 3 mg TID	Patients received daily orally one film-coated tablet of 1 milligram (mg) of avenciguat three times a day (TID) in Week 1 and Week 2. If the 1 mg TID medication was tolerated, up-titration to 2 mg avenciguat (one film-coated tablet of 2 mg) TID occurred after 2 weeks until Week 4 of treatment. Then if medication was tolerated, up-titration to 3 mg avenciguat (one film-coated tablet of 3 mg) TID occurred from Week 5 until Week 20. Avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	66	6	66	26	66
EG003	Placebo	This arm comprises all placebo treated participants. Participants were administered film-coated tablets of placebo matching avenciguat 1mg, 2mg or 3mg 3 times a day (TID) during 20 weeks of treatment. Placebo matching avenciguat had to be taken with a glass of water and could be taken with or without food. Patients continued the treatment until undue drug toxicity, disease progression, or withdrawal of consent, whichever occurred first.	64	6	64	21	64

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Haemorrhagic diathesis	Blood and lymphatic system disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0011 affected65 at risk EG0020 affected66 at risk EG0030 affected64 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0021 affected66 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0021 affected66 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Appendicitis noninfective	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Enteritis	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Chest pain	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0021 affected66 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0021 affected66 at risk EG003
Pneumonia	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0021 affected66 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0011 affected65 at risk EG0020 affected66 at risk EG003
Incision site haemorrhage	Injury, poisoning and procedural complications	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0011 affected65 at risk EG0020 affected66 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0021 affected66 at risk EG003
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.0	Systematic Assessment	EG0001 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0020 affected66 at risk EG003
Hypertensive urgency	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0010 affected65 at risk EG0021 affected66 at risk EG003
Hypotension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected64 at risk EG0011 affected65 at risk EG0020 affected66 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected64 at risk EG0013 affected65 at risk EG0026 affected66 at risk EG0034 affected64 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.0	Systematic Assessment	EG0002 affected64 at risk EG0010 affected65 at risk EG0024 affected66 at risk EG003
Fatigue	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0012 affected65 at risk EG0026 affected66 at risk EG003
Oedema peripheral	General disorders	MedDRA 26.0	Systematic Assessment	EG0000 affected64 at risk EG0014 affected65 at risk EG0025 affected66 at risk EG003
COVID-19	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 affected64 at risk EG0015 affected65 at risk EG0023 affected66 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 26.0	Systematic Assessment	EG0004 affected64 at risk EG0012 affected65 at risk EG0023 affected66 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA 26.0	Systematic Assessment	EG0001 affected64 at risk EG0013 affected65 at risk EG0025 affected66 at risk EG003
Headache	Nervous system disorders	MedDRA 26.0	Systematic Assessment	EG0005 affected64 at risk EG0011 affected65 at risk EG0025 affected66 at risk EG003
Hypotension	Vascular disorders	MedDRA 26.0	Systematic Assessment	EG0003 affected64 at risk EG0016 affected65 at risk EG0025 affected66 at risk EG003

ID	Term
D051437	Renal Insufficiency
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms