A Trial to Study Neladenoson Bialanate Over 20 Weeks in P... | NCT03098979

NCT03098979

ID	Type	Description	Link
2016-004062-26	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Neladenoson bialanate (BAY1067197) (5 mg)	Experimental	Chronic heart failure with preserved ejection fraction	Drug: Neladenoson bialanate (BAY1067197)
Neladenoson bialanate (BAY1067197) (10 mg)	Experimental	Chronic heart failure with preserved ejection fraction	Drug: Neladenoson bialanate (BAY1067197)
Neladenoson bialanate (BAY1067197) (20 mg)	Experimental	Chronic heart failure with preserved ejection fraction	Drug: Neladenoson bialanate (BAY1067197)
Neladenoson bialanate (BAY1067197) (30 mg)	Experimental	Chronic heart failure with preserved ejection fraction	Drug: Neladenoson bialanate (BAY1067197)
Neladenoson bialanate (BAY1067197) (40 mg)	Experimental	Chronic heart failure with preserved ejection fraction	Drug: Neladenoson bialanate (BAY1067197)
Placebo

Name	Type	Description	Arm Group Labels	Other Names
Neladenoson bialanate (BAY1067197)	Drug	5 mg orally once daily for 20 weeks	Neladenoson bialanate (BAY1067197) (5 mg)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment	The 6MWD test is designed to evaluate a subject's exercise capacity while performing an everyday activity.	Baseline, and up to 20 weeks of treatment

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity	AVIVO™ Mobile Patient Management System, a wearable wireless device worn by the subject, was used to monitor subjects' cardiovascular status. The patient's everyday physical activity e.g. duration, intensity, was also tracked by the AVIVO device. For Activity Intensity, the Unit of Measure is "percentage of maximum activity", and length of intervals is "daily".

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Bayer Study Director	Bayer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Northwestern University		Chicago	Illinois	60611	United States
St. Louis Heart & Vascular, PC

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31162568	Derived	Shah SJ, Voors AA, McMurray JJV, Kitzman DW, Viethen T, Bomfim Wirtz A, Huang E, Pap AF, Solomon SD. Effect of Neladenoson Bialanate on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA. 2019 Jun 4;321(21):2101-2112. doi: 10.1001/jama.2019.6717.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks
FG001	Neladenoson Bialanate 5 mg	Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Jun 15, 2018	May 20, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks
BG001	Neladenoson Bialanate 5 mg	Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks
BG002	Neladenoson Bialanate 10 mg	Subjects received 10 mg of neladenoson bialanate tablets orally for 20 weeks
BG003	Neladenoson Bialanate 20 mg	Subjects received 20 mg of neladenoson bialanate tablets orally for 20 weeks
BG004	Neladenoson Bialanate 30 mg	Subjects received 30 mg of neladenoson bialanate tablets orally for 20 weeks
BG005	Neladenoson Bialanate 40 mg	Subjects received 40 mg of neladenoson bialanate tablets orally for 20 weeks
BG006	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
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG00250 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

LVEF

Left ventricular ejection fraction (LVEF) is defined as the fraction of blood being pumped out of the left ventricle of the heart with each contraction.

Included subjects with valid baseline value for this characteristic

Mean

Standard Deviation

percentage of blood ejected

Title	Denominators	Categories
	ParticipantsBG00045 ParticipantsBG00120 ParticipantsBG002

NT-proBNP

N-terminal pro-hormone b-type natriuretic peptide

Included subjects with valid baseline value for this characteristic

Median

Full Range

pg/ml

Title	Denominators	Categories
	ParticipantsBG00063 ParticipantsBG00123 ParticipantsBG002

NYHA class

NYHA classes: I: No limitation of physical activity (PA). Ordinary PA does not cause undue fatigue, palpitation, dyspnea, or anginal pain II: Slight limitation of PA; comfortable at rest. Ordinary PA results in fatigue, palpitation, dyspnea, or anginal pain III: Marked limitation of PA; comfortable at rest. Less than ordinary PA causes fatigue, palpitation, dyspnea, or anginal pain IV: Inability to carry on any PA without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any PA is undertaken, discomfort is increased

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG001

Medical history: diabetes

Subjects with medical history of Type 2 diabetes mellitus

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

Medical history: Atrial fibrillation

Subjects with medical history of Atrial fibrillation

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

Medical history: hypertension

Subjects with medical history of hypertension

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

eGFR

eGFR = estimated glomerular filtration rate

Mean

Standard Deviation

mL/min/1.73 square meter

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

6MWD

6MWD = six-minute walking distance

Mean

Standard Deviation

meter

Title	Denominators	Categories
	ParticipantsBG00076 ParticipantsBG00127 ParticipantsBG002

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

Absolute Change From Baseline in 6-minute Walking Distance (6MWD) After 20 Weeks of Treatment

The 6MWD test is designed to evaluate a subject's exercise capacity while performing an everyday activity.

Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure, and it also included subjects who were censored due to cardiovascular (CV) death or hospitalization for heart failure (HF) that prevented assessment of efficacy at 20 weeks.

Posted

Mean

Standard Deviation

meter

Baseline, and up to 20 weeks of treatment

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks
OG001	Neladenoson Bialanate 5 mg	Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks
OG002	Neladenoson Bialanate 10 mg	Subjects received 10 mg of neladenoson bialanate tablets orally for 20 weeks
OG003	Neladenoson Bialanate 20 mg	Subjects received 20 mg of neladenoson bialanate tablets orally for 20 weeks
OG004	Neladenoson Bialanate 30 mg	Subjects received 30 mg of neladenoson bialanate tablets orally for 20 weeks
OG005	Neladenoson Bialanate 40 mg	Subjects received 40 mg of neladenoson bialanate tablets orally for 20 weeks

Units	Counts
Participants	OG00065 OG00122 OG00244 OG003

Title

Denominators

Categories

Value at baseline

Title	Measurements
	OG000329± 95 OG001306± 117 OG002300± 109 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 OG001 OG002 OG003 OG004 OG005		MCP-Mod method	Dose response relationship was assessed using the MCP-Mod method combining MCP principles with modeling techniques.	0.5183	Linear dose-response shape: The multiple comparison procedures (MCP) approach was applied to calculate the adjusted one-sided p-values of the contrast test.													Superiority

Secondary

Change From Baseline in Average Weekly Percentage of Maximum Possible Recorded Activity Intensity

AVIVO™ Mobile Patient Management System, a wearable wireless device worn by the subject, was used to monitor subjects' cardiovascular status. The patient's everyday physical activity e.g. duration, intensity, was also tracked by the AVIVO device. For Activity Intensity, the Unit of Measure is "percentage of maximum activity", and length of intervals is "daily".

Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure

Posted

Mean

Standard Deviation

percentage of maximum activity

Baseline, and up to 20 weeks of treatment

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks
OG001	Neladenoson Bialanate 5 mg	Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks
OG002	Neladenoson Bialanate 10 mg	Subjects received 10 mg of neladenoson bialanate tablets orally for 20 weeks
OG003

Secondary

Measured Values (Log Transformed) and Absolute Change in NT-proBNP From Baseline to 20 Weeks

NT-proBNP = N-terminal pro-hormone b-type natriuretic peptide

Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure

Posted

Median

Full Range

log (pg/ml)

Baseline, and up to 20 weeks of treatment

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks
OG001	Neladenoson Bialanate 5 mg	Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks
OG002	Neladenoson Bialanate 10 mg	Subjects received 10 mg of neladenoson bialanate tablets orally for 20 weeks
OG003	Neladenoson Bialanate 20 mg	Subjects received 20 mg of neladenoson bialanate tablets orally for 20 weeks

Secondary

Measured Values (Log-transformed) and Absolute Change in High Sensitivity Troponin T (Hs-TNT) From Baseline to 20 Weeks

High sensitivity troponin T (hs-TNT) was measured

Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure

Posted

Median

Full Range

log(pg/mL)

Baseline, and up to 20 weeks of treatment

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks
OG001	Neladenoson Bialanate 5 mg	Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks
OG002	Neladenoson Bialanate 10 mg	Subjects received 10 mg of neladenoson bialanate tablets orally for 20 weeks
OG003	Neladenoson Bialanate 20 mg	Subjects received 20 mg of neladenoson bialanate tablets orally for 20 weeks

Secondary

Measured Values and Absolute Change in 3 Scores From Kansas City Cardiomyopathy Questionnaire (KCCQ) From Baseline to 20 Weeks: Overall Summary Score, Physical Limitation Score and Total Symptom Score

The KCCQ is the leading health-related quality-of-life measure for patients with chronic heart failure (CHF). It is a 23-item questionnaire that independently measures the impact of patient's heart failure (HF), or its treatment, on 7 distinct domains: 1) Symptom Frequency 2) Symptom Burden 3) Physical Limitation 4) Quality of Life 5) Social Limitations 6) Self-efficacy 7) Symptoms Stability.

Overall summary score= mean score of (symptom frequency + symptom burden+ physical limitation + quality of life + social limitation); scores on a scale of 0 to 100, higher scores means better outcome; Physical Limitation: scores on a scale of 0 to 100, higher scores means better outcome; Total symptom score=mean score of (symptom frequency + symptom burden): scores on a scale of 0 to 100, higher scores means better outcome.

Positive change means improvement and negative change means deterioration.

Per-protocol set (PPS): Included all full analysis set (FAS) population subjects without validity findings for this outcome measure

Posted

Mean

Standard Deviation

scores on a scale

Baseline, and up to 20 weeks of treatment

ID	Title	Description
OG000	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks
OG001	Neladenoson Bialanate 5 mg

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	Placebo	Subjects received placebo matched to neladenoson bialanate tablets orally for 20 weeks.	2	76	21	76	24	76
EG001	Neladenoson Bialanate 5mg	Subjects received 5 mg of neladenoson bialanate tablets orally for 20 weeks.	0	27	9	27	13	27
EG002	Neladenoson Bialanate 10mg	Subjects received 10 mg of neladenoson bialanate tablets orally for 20 weeks.	2	50	11	50	14	50
EG003	Neladenoson Bialanate 20mg	Subjects received 20 mg of neladenoson bialanate tablets orally for 20 weeks.	1	51	11	51	22	51
EG004	Neladenoson Bialanate 30mg	Subjects received 30 mg of neladenoson bialanate tablets orally for 20 weeks.	1	50	14	50	17	50
EG005	Neladenoson Bialanate 40mg	Subjects received 40 mg of neladenoson bialanate tablets orally for 20 weeks.	1	51	16	51	24	51

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG0030 events0 affected51 at risk EG0041 events1 affected50 at risk EG0050 events0 affected51 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Bradycardia	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected76 at risk EG0012 events2 affected27 at risk EG0023 events3 affected50 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Cardiac failure chronic	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0007 events3 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Mitral valve incompetence	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Sinoatrial block	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Sinus arrest	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Sinus bradycardia	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Tricuspid valve incompetence	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Ventricular extrasystoles	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Acute left ventricular failure	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Cataract	Eye disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Mallory-Weiss syndrome	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Oedema peripheral	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Cholangitis acute	Hepatobiliary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Bronchitis	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Influenza	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Otitis media chronic	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0002 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Pneumonia	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Pneumonia pneumococcal	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Wound infection	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Pulmonary sepsis	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Pneumonia bacterial	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Spinal fracture	Injury, poisoning and procedural complications	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Arteriogram coronary	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Blood glucose increased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Influenza A virus test positive	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0002 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Metastases to liver	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Cerebral haemorrhage	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Intraventricular haemorrhage	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Syncope	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Basal ganglia haemorrhage	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0021 events1 affected50 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0004 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Hip arthroplasty	Surgical and medical procedures	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Inguinal hernia repair	Surgical and medical procedures	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Insertion of ambulatory peritoneal catheter	Surgical and medical procedures	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Hysterosalpingectomy	Surgical and medical procedures	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Aortic stenosis	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Hypertensive crisis	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Peripheral ischaemia	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Venous thrombosis limb	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Device dislocation	Product Issues	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0005 events5 affected76 at risk EG0010 events0 affected27 at risk EG0023 events3 affected50 at risk EG0031 events1 affected51 at risk EG0041 events1 affected50 at risk EG0056 events4 affected51 at risk
Cardiac failure	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0005 events5 affected76 at risk EG0013 events2 affected27 at risk EG0023 events3 affected50 at risk EG003
Ventricular tachycardia	Cardiac disorders	MedDRA (21.0)	Non-systematic Assessment	EG0005 events3 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events3 affected76 at risk EG0010 events0 affected27 at risk EG0022 events2 affected50 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected27 at risk EG0021 events1 affected50 at risk EG003
Fatigue	General disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (21.0)	Non-systematic Assessment	EG0006 events5 affected76 at risk EG0011 events1 affected27 at risk EG0023 events3 affected50 at risk EG003
Blood creatinine increased	Investigations	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events3 affected76 at risk EG0012 events2 affected27 at risk EG0020 events0 affected50 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (21.0)	Non-systematic Assessment	EG0005 events4 affected76 at risk EG0010 events0 affected27 at risk EG0020 events0 affected50 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Dizziness	Nervous system disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events1 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0011 events1 affected27 at risk EG0021 events1 affected50 at risk EG003
Chronic kidney disease	Renal and urinary disorders	MedDRA (21.0)	Non-systematic Assessment	EG0000 events0 affected76 at risk EG0012 events2 affected27 at risk EG0020 events0 affected50 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0001 events1 affected76 at risk EG0010 events0 affected27 at risk EG0021 events1 affected50 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Non-systematic Assessment	EG0003 events3 affected76 at risk EG0012 events2 affected27 at risk EG0022 events2 affected50 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected76 at risk EG0011 events1 affected27 at risk EG0021 events1 affected50 at risk EG003
Hypertension	Vascular disorders	MedDRA (21.0)	Non-systematic Assessment	EG0002 events2 affected76 at risk EG0011 events1 affected27 at risk EG0020 events0 affected50 at risk EG003

ID	Term
D006333	Heart Failure

ID	Term
C000623125	neladenoson bialanate

ParticipantsBG006305

ParticipantsBG006194

ParticipantsBG006255

ParticipantsBG006305

OG000
OG001
OG002
OG003
OG004
OG005

Subjects received 5 milligrams (mg) of neladenoson bialanate tablets orally for 20 weeks

EG0041 events1 affected50 at risk