Effect of Elamipretide on Left Ventricular Function in Su... | NCT02788747

ID	Type	Description	Link
2014-005724-10	EudraCT Number

Label	Type	Description	Intervention Names
4 mg elamipretide	Experimental	4 mg elamipretide once daily for 28 consecutive days	Drug: 4 mg elamipretide
40 mg elamipretide	Experimental	40 mg elamipretide once daily for 28 consecutive days	Drug: 40 mg elamipretide
Placebo	Placebo Comparator	Placebo once daily for 28 consecutive days	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
4 mg elamipretide	Drug	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days	4 mg elamipretide

Measure	Description	Time Frame
Change in Left Ventricular End Systolic Volume (ml)	Change in left ventricular end systolic volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.	Baseline to Week 4

Measure	Description	Time Frame
Change in Left Ventricular Ejection Fraction (% of Blood Volume)	Change in Left Ventricular Ejection Fraction as measured by percentage of blood volume from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.	Baseline to Week 4
Change in Left Ventricular End Diastolic Volume (ml) as Measured by MRI

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Willing and able to provide signed informed consent form (ICF) prior to participation in any study-related procedures.
Age ≥40 and ≤80 years.
A known history of chronic ischemic or non-ischemic cardiomyopathy of at least 6 months duration from the time of the initial diagnosis.
Receiving heart failure (HF) treatment, including, but not limited to, angiotensin converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), and an evidence-based beta blocker for the treatment of HF. Subjects who cannot tolerate ACEI or ARB due to reduced renal function or hypotension are eligible. Subjects may be receiving aldosterone antagonists, but this is not a requirement for the study.
HF is considered to be stable in the judgment of the Investigator AND doses of HF treatment have been stable for at least 1 month prior to the Screening Visit.
In normal sinus rhythm (electrocardiogram documented) at Screening and Day 1 and no history of atrial fibrillation in the past 12 months
No hospitalization related to HF within 1 month prior to the Screening Visit.
Left Ventricular Ejection Fraction (LVEF) ≤ 40% by 2-D echocardiography at Screening.
At least 3 viable segments (hyperenhancement ≤ 25%) by a qualifying delayed gadolinium-enhanced cardiac MRI examination at Screening (confirmed by independent core lab).
Women of childbearing potential must agree to use 1 of the following methods of birth control from the date they sign the ICF until two months after the last dose of study medication:
- Abstinence, maintenance of monogamous relationship with a male partner who has been surgically sterilized by vasectomy, or barrier method AND either hormonal contraception or an intrauterine device or system.

Exclusion Criteria:

History of any concurrent medical condition which, in the opinion of the Investigator, significantly increased the potential risks associated with administration of study medication or any other aspect of study participation.
Any contraindication to MRI scanning.
Left ventricular end diastolic dimension (LVEDD) indexed to Body Surface Area is > 45 mm/m2.
Coronary or peripheral revascularization procedures, valvular procedures, OR any major surgical procedure within 3 months prior to the Screening Visit.
Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 3 months prior to the Screening Visit.
Obstructive or restrictive cardiomyopathy, infiltrative diseases of the myocardium (e.g., amyloid, sarcoid, etc.) myocarditis, or reductions in LV function thought to be secondary primarily to valvular heart disease, prior cardiac valve surgery or known aortic stenosis.
The presence or anticipated placement of any pacemaker, implantable cardioverter defibrillator (ICD), or cardiac resynchronization therapy (CRT) devices during the ensuing 6-week study period.
Presence of second degree or advanced heart block.
Uncontrolled hypertension defined as a systolic blood pressure > 160 mmHg or a diastolic blood pressure > 110 mmHg on at least two consecutive readings.
Presence of any left ventricular thrombus, pericardial disease, uncorrected thyroid disease or a dyskinetic left ventricular aneurysm.
History of cancer that causes symptoms, disabilities, or is likely to lead to hospitalization or treatment in the next 12 months.
Currently receiving treatment with chemotherapeutic agents or immunosuppressant agents or has received prior radiation therapy to the chest.
Liver enzymes (alanine aminotransferase [ALT] AND/OR aspartate. aminotransferase [AST]) elevation > 3 times the upper limit of normal (ULN).
Total bilirubin > 1.5 times ULN in the absence of Gilbert's Syndrome.
Bleeding diathesis or any known blood dyscrasia.
Anemia, defined as hemoglobin < 9 g/dL or planned blood transfusions in the next 6 weeks.
Estimated glomerular filtration rate (eGFR) < 30 mL/min, using the Modification of Diet in Renal Disease (MDRD) Study equation.
History of hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection, or diagnosis of immunodeficiency.
Known active drug or alcohol abuse within 1 year of the Screening Visit. Alcohol abuse is defined as 15 or more drinks for men per week or 8 or more for women.
Recipient of any investigational drugs, stem cell or gene therapies, or devices OR participation in another clinical trial, within 3 months prior to the Screening Visit.
Female subjects who are pregnant, planning to become pregnant, or lactating.
Requiring any change in doses of cardiovascular medication (including diuretics) in order to control worsening of HF symptoms.
Known allergy to gadolinium.
Currently receiving treatment with therapeutic doses of anticoagulants. Antiplatelet therapy used to prevent cardiovascular disease (primary prevention) or to treat chronic disease (secondary prevention) is permitted.
Currently receiving treatment with sacubitril/valsartan or trimetazidine.
Hyponatremia defined as plasma Na+ level <125 mEq/L (UK only).

Name	Affiliation	Role
Gerasimos Filippatos, MD	University of Athens, School of Medicine, Athens, Greece	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
A.O. Papa Giovanni XXIII Cardiologia 1, Torre 5		Bergamo		24127	Italy
A.O. Spedali Civili di Brescia Cardiologia

ID	Title	Description
FG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
FG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 21, 2017	Apr 6, 2020

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 in Left Ventricular End Systolic Volume (ml)

Change in left ventricular end systolic volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom left ventricular end systolic volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	4 mg elamipretide: subcutaneous injection administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	40 mg elamipretide: subcutaneous injection administered once daily for 28 consecutive days
OG002	Placebo	Placebo: subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants	OG00022 OG00124 OG00223

Title

Denominators

Categories

Title	Measurements
	OG000-4.4± 6.50 OG001-1.2± 9.04 OG002-3.8± 5.85

Secondary

Change in Left Ventricular Ejection Fraction (% of Blood Volume)

Change in Left Ventricular Ejection Fraction as measured by percentage of blood volume from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for Left Ventricular Ejection Fraction was measured at baseline and Week 4

Posted

Mean

Standard Deviation

percentage of blood volume

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Left Ventricular End Diastolic Volume (ml) as Measured by MRI

Change from baseline in Left Ventricular End Diastolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom Left Ventricular End Diastolic Volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Left Ventricular Stroke Volume (ml)

Change in Left Ventricular Stroke Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom Left Ventricular Stroke Volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Left Ventricular Cardiac Output (L/Min)

Change in Left Ventricular Cardiac Output as measured by L/min from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom Left Ventricular Cardiac Output was measured at baseline and Week 4

Posted

Mean

Standard Deviation

L/min

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Left Ventricular Myocardial Mass (g)

Change in Left Ventricular Myocardial Mass as measured by grams from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom Left Ventricular Myocardial Mass was measured at baseline and Week 4

Posted

Mean

Standard Deviation

grams

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Right Ventricular End Systolic Volume (mL)

Change in Right Ventricular End Systolic Volume as measured by mL from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom Right Ventricular End Systolic Volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Right Ventricular End Diastolic Volume (mL)

Change in Right Ventricular End Diastolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom Right Ventricular End Diastolic Volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Right Ventricular Ejection Fraction (% Blood Volume)

Change in Right Ventricular Ejection Fraction as measured by percentage of blood volume from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by MRI.

All participants for whom Right Ventricular Ejection Fraction was measured at baseline and Week 4

Posted

Mean

Standard Deviation

percentage of blood volume

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Early and Late Mitral Inflow Velocity Ratio

Change in Early and Late Mitral Inflow Velocity Ratio from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Early and Late Mitral Inflow Velocity Ratio was measured at baseline and Week 4

Posted

Mean

Standard Deviation

ratio

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Early Mitral Inflow Velocity and Mitral Annular Early Diastolic Velocity Ratio (E/e')

Change in Early Mitral Inflow Velocity and Mitral Annular Early Diastolic Velocity Ratio as measured by E/e' from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Early Mitral Inflow Velocity and Mitral Annular Early Diastolic Velocity Ratio was measured at baseline and Week 4

Posted

Mean

Standard Deviation

ratio

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts

Secondary

Change in Left Atrial Volume (mL)

Change in Left Atrial Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Left Atrial Volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Left Ventricular Global Longitudinal Strain Assessment (%)

Change in Left Ventricular Global Longitudinal Strain Assessment as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Left Ventricular Global Longitudinal Strain Assessment was measured at baseline and Week 4

Posted

Mean

Standard Deviation

percentage of myocardial length change

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Left Ventricular End Diastolic Volume (mL) as Measured by Echocardiography

Change in Left Ventricular End Diastolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Left Ventricular End Diastolic Volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Left Ventricular End Systolic Volume (mL) as Measured by Echocardiography

Change in Left Ventricular End Systolic Volume as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Left Ventricular End Systolic Volume was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Biplane Ejection Fraction (mL)

Change in Biplane Ejection Fraction as measured by ml from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Biplane Ejection Fraction was measured at baseline and Week 4

Posted

Mean

Standard Deviation

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Left Ventricular Mass Assessment (g)

Change in Left Ventricular Mass Assessment as measured by grams from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Left Ventricular Mass was measured at baseline and Week 4

Posted

Mean

Standard Deviation

grams

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Tricuspid Regurgitation Severity Assessment (cm²)

Change in Tricuspid Regurgitation Severity Assessment as measured by cm from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Tricuspid Regurgitation Severity Assessment was measured at baseline and Week 4

Posted

Mean

Standard Deviation

cm²

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Right Ventricular Fractional Area (%)

Change Right Ventricular Fractional Area in as measured by percentage from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Right Ventricular Fractional Area was measured at baseline and Week 4

Posted

Mean

Standard Deviation

percentage of area

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Right Ventricular Systolic Pressure (mmHg)

Change in Change in Right Ventricular Systolic Pressure as measured by mmHg from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Right Ventricular Systolic Pressure was measured at baseline and Week 4

Posted

Mean

Standard Deviation

mmHg

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Secondary

Change in Mitral Regurgitation Severity (cm²)

Change in Mitral Regurgitation Severity as measured by cm² from baseline (last assessment prior to start of study) to Week 4 (end of treatment visit) as assessed by echocardiography.

All participants for whom Mitral Regurgitation Severity was measured at baseline and Week 4

Posted

Mean

Standard Deviation

cm²

Baseline to Week 4

ID	Title	Description
OG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
OG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
OG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days

Units	Counts
Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Deep vein thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Hypotension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Increased Blood bilirubin	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Eosinphil count increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Troponin I increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0011 affected25 at risk EG0021 affected24 at risk
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0020 affected24 at risk
Sciatica	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected22 at risk EG0011 affected25 at risk EG0021 affected24 at risk
Somnolence	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Injection site erythema	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Injection site haemorrhage	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0020 affected24 at risk
Injection site induration	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Injection site mass	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Injection site pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Oedema peripheral	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Insomia	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0021 affected24 at risk
Anxiety	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0020 affected24 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0021 affected24 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Albuminiuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Haematuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Renal impairment	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0020 affected24 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0020 affected24 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Gout	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Hyperkalemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0010 affected25 at risk EG0021 affected24 at risk
Hypokalemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0012 affected25 at risk EG0021 affected24 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0020 affected24 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected22 at risk EG0010 affected25 at risk EG0020 affected24 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected22 at risk EG0011 affected25 at risk EG0020 affected24 at risk

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases

ID	Title	Description
BG000	4 mg Elamipretide	Subcutaneous injection of 4 mg elamipretide administered once daily for 28 consecutive days
BG001	40 mg Elamipretide	Subcutaneous injection of 40 mg elamipretide administered once daily for 28 consecutive days
BG002	Placebo	Subcutaneous injection of placebo administered once daily for 28 consecutive days
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	4 mg Elamipretide	4 mg elamipretide: subcutaneous injection administered once daily for 28 consecutive days	22	0	22	9	22
EG001	40 mg Elamipretide	40 mg elamipretide: subcutaneous injection administered once daily for 28 consecutive days	25	1	25	16	25
EG002	Placebo	Placebo: subcutaneous injection of placebo administered once daily for 28 consecutive days	24	0	24	10	24