Dilated Cardiomyopathy, Lamin A/C Gene Mutation
Conditions
Keywords
cardiomyopathy, Lamin Type A, heart failure, ARRY-797, C4411002
Brief summary
This is a randomized, double-blind, placebo-controlled study in patients with dilated cardiomyopathy (DCM) due to a mutation of the gene encoding the lamin A/C protein (LMNA). The study will further evaluate a dose level of study drug (ARRY-371797) that has shown preliminary efficacy and safety in this patient population. After the primary analysis has been performed, eligible patients may receive open-label treatment with ARRY-371797.
Interventions
DRUGARRY-371797 (PF-07265803)
400 mg twice daily (BID)
OTHERPlacebo
BID
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
During the randomized, double-blind period, patients, Investigators, site personnel and the sponsor personnel directly involved with the conduct of the study will remain blinded to assigned treatment, except for regulatory reporting requirements.
Intervention model description
The study will be conducted in 2 parts: a randomized, double-blind treatment period for at least 24 weeks, followed by an ARRY-371797 (PF-07265803) open-label treatment period.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Selected Key Inclusion Criteria: * Patients with symptomatic lamin A/C protein (LMNA)-related cardiomyopathy Class II/III/ or Class IV defined as: * Gene positive for a pathogenic, likely pathogenic, or VUS mutation in the LMNA gene as determined by an accredited clinical laboratory. * Evidence of cardiac impairment in LVEF \<= 50% * Patient will have an implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator (ICD/CRT-D). ICD implanted at least 4 weeks prior to initiation of study treatment or CRT-D initiated at least 6 months prior to initiation of study treatment and defibrillation function activated at least 4 weeks prior to initiation of study treatment. * Class II/III patients must have objective functional impairment evidenced by a reduction in 6-minute walk test (6MWT); a. Screening: 6MWT distance \>100 m but ≤450 m, AND b. Day -1 visit: 6MWT distance \>100 m but ≤485 m, AND c. Baseline visit (Day 1): 6MWT distance \>100 m but ≤485 * Class II/III patients must be stable for at least 3 months * Stable medical and/or device therapy consistent with regional American Heart Association (AHA) / American College of Cardiology (ACC) or European Society of Cardiology (ESC) guidelines at the investigator discretion, without change in heart failure drug(s) dose in the past 1 month. * Patients must meet acceptable hematology, hepatic and renal laboratory values within 35 days prior to Day 1 as specified in the protocol. Selected Key
Exclusion criteria
* Presence of other form(s) of cardiomyopathy contributing to HF (eg, inflammatory or infiltrative cardiomyopathy), clinically significant cardiac anatomic abnormality (eg,LV aneurysm), clinically significant coronary artery disease (eg, coronary revascularization, exercise induced angina) or uncorrected, hemodynamically significant (ie, moderate-severe) primary structural valvular disease not due to HF, per investigator judgment. * Currently receiving intermittent or continuous IV inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation. Participants listed for cardiac transplantation may be enrolled provided transplantation is not likely to occur in the next 6 months. * Myocardial infarction, cardiac surgical procedures (other than for pacemaker/ICD/CRT-D implantation or replacement), acute coronary syndrome, serious systemic infection with evidence of septicemia, or any major surgical procedure requiring general anesthesia within 3 months prior to screening. * Currently receiving or deemed at high risk of requiring chronic renal replacement therapy (eg, hemodialysis or peritoneal dialysis) within 6 months. * Initiation of CRT within 6 months prior to screening. * Treatment with any investigational agent(s) for HF within 35 days prior to Day 1. * Malignancy that is active or has been diagnosed within 3 years prior to screening, except surgically curatively resected in situ malignancies or surgically cured early breast cancer, prostate cancer, skin cancer (basal cell carcinoma, squamous cell carcinoma), thyroid cancer, or cervical cancer, or, with prior review by the medical monitor, other early stage surgically curatively resected malignancies with less than a 20% expected 2 year recurrence rate. * Non-cardiac condition that limits lifespan to \< 1 year. * Serum positive for hepatitis B surface antigen, viremic hepatitis C, or human immunodeficiency virus (HIV) at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24 | Baseline, Week 24 | The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional. Study discontinuation & death were incorporated into endpoint definition through ranking in hypothesis testing of treatment difference. Missing data resulting from study discontinuation were imputed using control-based multiple imputation method to estimate treatment effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Baseline, Week 12, Week 24 | The KCCQ measured the effects of symptoms, functional (physical) limitations, and psychological distress on an individual's health-related quality of life. It contains 23 items, which assessed the ability to perform activities of daily living, frequency and severity of symptoms, the impact of these symptoms, and health-related quality of life. PL was a single questionnaire with score range of 0 to 100, where higher scores reflected better physical functioning status. TSS included frequency and severity of symptoms, and the impact of these symptoms. TSS scores were transformed to a range of 0 to 100, where higher scores reflected better health status. |
| Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12, Week 24 | PGI-S is a global index that rate the severity of the disease using a 5-point scale. In this outcome the number of participants with improvements in PGI-S the severity of their heart failure symptoms and in the severity of their PL were reported. Measured by the scale of: none, mild, moderate, severe or very severe (listed from better to worse). |
| Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12, Week 24 | PGI-C is a global index that rate the severity of the disease using a 7-point scale. In this outcome the number participants with improvements in their heart failure symptoms and in their physical activity limitations?, were reported. Measured by the scale of: very much better, moderately better, a little better, no change, a little worse, moderately worse, very much worse (listed from better to worse). |
| Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24 | Baseline, Week 4, Week 12, Week 24 | NT pro-BNP is a cardiac biomarker that is released in the blood in response to changes in the pressure inside of the heart. Levels go up when heart failure develops or gets worse, and levels go down when heart failure is stable or improves. This biomarker helps to measure the changes in the severity of heart failure over time in response to therapy. |
| Composite Time to First Occurrence of All-Cause Mortality or Worsening Heart Failure (WHF) | Maximum up to 212.28 weeks (maximum exposure was 208 weeks) | Defined as the time from randomization to the first occurrence of any event of death due to any cause, or worsening heart failure (HF-related hospitalization or HF-related urgent care visit). Kaplan-Meier method and cox regression model were used for analysis. |
| Change From Baseline in 6 MWT at Weeks 4 and 12 | Baseline, Week 4, Week 12 | The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional. |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity | Maximum up to 212.28 weeks (maximum exposure was of 208 weeks) | An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all Non-SAEs. Grade \>=3 AEs meant severe AEs. |
| Number of Participants With Laboratory Test Abnormalities | Maximum up to 212.28 weeks (maximum exposure was of 208 weeks) | Following parameters were analyzed for laboratory examination: hematology (eosinophils, erythrocytes, hemoglobin, hematocrit, granulocytes, leukocytes, lymphocytes, monocytes, platelets, neutrophils, nucleated erythrocytes); blood chemistry (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, C-reactive protein, calcium, chloride, creatinine, creatine kinase, epidermal growth factor receptor, follicle stimulating hormone, gamma glutamyl transferase, glucose, magnesium, N-Terminal ProB-type natriuretic peptide, phosphate, potassium, protein, sodium, potassium, thyrotropin, troponin I, troponin T, urate). |
| Number of Participants According to Categorization of Abnormal Vital Signs | Maximum up to 212.28 weeks (maximum exposure was of 208 weeks) | Following vital sign parameters were assessed: diastolic blood pressure, systolic blood pressure, heart rate, and body weight. Vital sign abnormalities criteria included: a) systolic blood pressure (mmHg): decrease (change \<= -20, or value \<90) and increase (change \>=20, or value \>140); b) diastolic blood pressure (mmHg): decrease (change \<= -15, or value \<60) and increase (change \>=15, or value \>90); c) heart Rate (bpm) decrease: (change \<= -15, or value \<50) and increase (change \>=15, or value \>100); d) weight: (kg) decrease (Change \<= -7%) and increase (Change \> =7%). |
| Number of Participants According to Categorization of Electrocardiogram (ECG) Data | Maximum up to 212.28 weeks (maximum exposure was of 208 weeks) | Following parameters were analyzed: heart rate, QT interval, corrected QT (QTc) interval, Bazett's correction QT (QTcB) interval, and Fridericia's correction (QTcF) interval. Criteria for notable ECG values were as follows: QT interval (in millisecond \[msec\]) new (newly occurring post-baseline value) greater than (\>) 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; heart rate in bpm new (newly occurring post-baseline value) \<60 and \>100. |
| Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Baseline, Week 12, Week 24 | Arrhythmia assessment: incidence of new and clinically significant ventricular or atrial arrhythmias was assessed by an implantable cardioverter defibrillator (ICD) or CRT defibrillator (CRT-D) applicable device interrogations. |
| Overall Survival (OS) | From randomization up to death due to any cause or censored date, maximum up to 212.28 weeks (maximum exposure was of 208 weeks) | OS was defined as time from randomization to death due to any cause. Participants who did not have a death date were censored for OS at their last contact date. Kaplan-Meier method and cox regression model were used for analysis. |
Countries
Argentina, Belgium, Canada, Italy, Mexico, Netherlands, Norway, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 77 participants with Lamin A/C protein (LMNA)-related dilated cardiomyopathy (DCM) in New York heart association (NYHA) functional Class II and III were enrolled in the study. All participants enrolled received at least 1 dose of study intervention.
Participants by arm
| Arm | Count |
|---|---|
| PF-07265803 (ARRY-371797) Participants were randomized to receive PF-07265803 400 mg (4\*100 mg tablets) twice daily (BID). | 40 |
| Placebo Participants were randomized to receive placebo matched to PF-07265803 BID. | 37 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment Period | Death | 1 | 2 |
| Double-Blind Treatment Period | Lost to Follow-up | 2 | 0 |
| Double-Blind Treatment Period | Other | 4 | 1 |
| Double-Blind Treatment Period | Study Termination by Sponsor | 29 | 32 |
| Double-Blind Treatment Period | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | PF-07265803 (ARRY-371797) | Placebo | Total |
|---|---|---|---|
| Age, Customized 18-34 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Customized 35-49 years | 15 Participants | 10 Participants | 25 Participants |
| Age, Customized 50-64 years | 17 Participants | 19 Participants | 36 Participants |
| Age, Customized >= 65 years | 4 Participants | 7 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 33 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 36 Participants | 74 Participants |
| Sex: Female, Male Female | 18 Participants | 15 Participants | 33 Participants |
| Sex: Female, Male Male | 22 Participants | 22 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 40 | 3 / 37 |
| other Total, other adverse events | 31 / 40 | 27 / 37 |
| serious Total, serious adverse events | 10 / 40 | 21 / 37 |
Outcome results
Primary
Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24
The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional. Study discontinuation & death were incorporated into endpoint definition through ranking in hypothesis testing of treatment difference. Missing data resulting from study discontinuation were imputed using control-based multiple imputation method to estimate treatment effect.
Time frame: Baseline, Week 24
Population: Efficacy analysis set (EAS): NYHA functional Class II / III randomized participants. 'Number of Participants Analyzed' = participants evaluable for the outcome measure. Five participants (ARRY-371797 \[n=3\], placebo \[n=2\]) discontinued the study before week 24 due to the sponsor's decision to terminate and were excluded from the primary analysis. All participants reported under 'Number of Participants Analyzed' contributed data to table but may not have evaluable data for every row.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-07265803 (ARRY-371797) | Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24 | Baseline | 402.500 Meter |
| PF-07265803 (ARRY-371797) | Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24 | Week 24 | 420.234 Meter |
| PF-07265803 (ARRY-371797) | Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24 | Week 24 change from baseline | 20.996 Meter |
| Placebo | Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24 | Baseline | 393.935 Meter |
| Placebo | Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24 | Week 24 | 393.455 Meter |
| Placebo | Change From Baseline in Six-Minute Walk Test (6 MWT) at Week 24 | Week 24 change from baseline | 2.679 Meter |
p-value: 0.81895% CI: [-24.246, 34.118]Van Elteren test
Secondary
Change From Baseline in 6 MWT at Weeks 4 and 12
The 6 MWT was an assessment where the distance that a participant could walk on a flat and hard surface in 6 minutes was measured. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed, and under supervision of a qualified professional.
Time frame: Baseline, Week 4, Week 12
Population: EAS included all NYHA functional Class II or III randomized participants. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-07265803 (ARRY-371797) | Change From Baseline in 6 MWT at Weeks 4 and 12 | Change at Week 4 | 15.40 Meter |
| PF-07265803 (ARRY-371797) | Change From Baseline in 6 MWT at Weeks 4 and 12 | Change at Week 12 | 21.47 Meter |
| Placebo | Change From Baseline in 6 MWT at Weeks 4 and 12 | Change at Week 4 | -2.60 Meter |
| Placebo | Change From Baseline in 6 MWT at Weeks 4 and 12 | Change at Week 12 | 10.00 Meter |
Secondary
Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24
The KCCQ measured the effects of symptoms, functional (physical) limitations, and psychological distress on an individual's health-related quality of life. It contains 23 items, which assessed the ability to perform activities of daily living, frequency and severity of symptoms, the impact of these symptoms, and health-related quality of life. PL was a single questionnaire with score range of 0 to 100, where higher scores reflected better physical functioning status. TSS included frequency and severity of symptoms, and the impact of these symptoms. TSS scores were transformed to a range of 0 to 100, where higher scores reflected better health status.
Time frame: Baseline, Week 12, Week 24
Population: EAS included all NYHA functional Class II or III randomized participants. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, Number Analyzed signifies participants evaluable for specified rows.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-07265803 (ARRY-371797) | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 12 Physical Limitation (PL) | 4.48 Units on a scale | Standard Deviation 11.373 |
| PF-07265803 (ARRY-371797) | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 24 Physical Limitation (PL) | 2.98 Units on a scale | Standard Deviation 17.51 |
| PF-07265803 (ARRY-371797) | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 12 Total Symptom Score (TSS) | 3.66 Units on a scale | Standard Deviation 12.487 |
| PF-07265803 (ARRY-371797) | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 24 Total Symptom Score (TSS) | 4.02 Units on a scale | Standard Deviation 19.171 |
| Placebo | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 24 Total Symptom Score (TSS) | -0.94 Units on a scale | Standard Deviation 14.981 |
| Placebo | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 12 Physical Limitation (PL) | -1.17 Units on a scale | Standard Deviation 15.326 |
| Placebo | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 12 Total Symptom Score (TSS) | 1.04 Units on a scale | Standard Deviation 16.491 |
| Placebo | Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical Limitation (PL) and Total Symptom Score (TSS) Domain Scores at Weeks 12 and 24 | Week 24 Physical Limitation (PL) | 1.21 Units on a scale | Standard Deviation 14.104 |
Secondary
Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24
NT pro-BNP is a cardiac biomarker that is released in the blood in response to changes in the pressure inside of the heart. Levels go up when heart failure develops or gets worse, and levels go down when heart failure is stable or improves. This biomarker helps to measure the changes in the severity of heart failure over time in response to therapy.
Time frame: Baseline, Week 4, Week 12, Week 24
Population: EAS included all NYHA functional Class II or III randomized participants. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-07265803 (ARRY-371797) | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24 | Change at Week 4 | -43.89 picomoles per liter | Standard Deviation 65.465 |
| PF-07265803 (ARRY-371797) | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24 | Change at Week 12 | -36.40 picomoles per liter | Standard Deviation 69.228 |
| PF-07265803 (ARRY-371797) | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24 | Change at Week 24 | 5.00 picomoles per liter | Standard Deviation 236.643 |
| Placebo | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24 | Change at Week 4 | -3.07 picomoles per liter | Standard Deviation 62.745 |
| Placebo | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24 | Change at Week 12 | -0.70 picomoles per liter | Standard Deviation 54.87 |
| Placebo | Change From Baseline in N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) at Weeks 4, 12, and 24 | Change at Week 24 | 24.37 picomoles per liter | Standard Deviation 134.225 |
Secondary
Composite Time to First Occurrence of All-Cause Mortality or Worsening Heart Failure (WHF)
Defined as the time from randomization to the first occurrence of any event of death due to any cause, or worsening heart failure (HF-related hospitalization or HF-related urgent care visit). Kaplan-Meier method and cox regression model were used for analysis.
Time frame: Maximum up to 212.28 weeks (maximum exposure was 208 weeks)
Population: The safety analysis set (SAS) included all participants who received at least 1 dose of study intervention regardless of NYHA functional class.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-07265803 (ARRY-371797) | Composite Time to First Occurrence of All-Cause Mortality or Worsening Heart Failure (WHF) | NA Weeks |
| Placebo | Composite Time to First Occurrence of All-Cause Mortality or Worsening Heart Failure (WHF) | NA Weeks |
p-value: 0.225795% CI: [0.13, 1.39]Log Rank
Secondary
Number of Participants According to Categorization of Abnormal Vital Signs
Following vital sign parameters were assessed: diastolic blood pressure, systolic blood pressure, heart rate, and body weight. Vital sign abnormalities criteria included: a) systolic blood pressure (mmHg): decrease (change \<= -20, or value \<90) and increase (change \>=20, or value \>140); b) diastolic blood pressure (mmHg): decrease (change \<= -15, or value \<60) and increase (change \>=15, or value \>90); c) heart Rate (bpm) decrease: (change \<= -15, or value \<50) and increase (change \>=15, or value \>100); d) weight: (kg) decrease (Change \<= -7%) and increase (Change \> =7%).
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Population: The SAS included all participants who received at least 1 dose of study intervention regardless of NYHA functional class. Here, Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Systolic Blood Pressure (mmHg): Decrease | 22 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Heart Rate (bpm): Decrease | 7 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Diastolic Blood Pressure (mmHg): Decrease | 28 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Heart Rate (bpm): Increase | 15 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Systolic Blood Pressure (mmHg): Increase | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Weight (kg): Decrease | 10 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Weight (kg): Increase | 5 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Abnormal Vital Signs | Diastolic Blood Pressure (mmHg): Increase | 7 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Weight (kg): Increase | 1 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Systolic Blood Pressure (mmHg): Decrease | 17 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Systolic Blood Pressure (mmHg): Increase | 14 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Diastolic Blood Pressure (mmHg): Decrease | 22 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Diastolic Blood Pressure (mmHg): Increase | 18 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Heart Rate (bpm): Decrease | 9 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Heart Rate (bpm): Increase | 10 Participants |
| Placebo | Number of Participants According to Categorization of Abnormal Vital Signs | Weight (kg): Decrease | 7 Participants |
Secondary
Number of Participants According to Categorization of Electrocardiogram (ECG) Data
Following parameters were analyzed: heart rate, QT interval, corrected QT (QTc) interval, Bazett's correction QT (QTcB) interval, and Fridericia's correction (QTcF) interval. Criteria for notable ECG values were as follows: QT interval (in millisecond \[msec\]) new (newly occurring post-baseline value) greater than (\>) 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) \> 450, 480, 500, increase from baseline \>30, increase from baseline \>60; heart rate in bpm new (newly occurring post-baseline value) \<60 and \>100.
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Population: The SAS included all participants who received at least 1 dose of study intervention regardless of NYHA functional class. Here, Number of Participants Analyzed signifies number of participants evaluable for this outcome measure and Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): Increase from baseline >30 | 12 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): Increase from baseline >30 | 11 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): New >480 | 10 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): Increase from baseline >60 | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): New >450 | 5 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): New >450 | 7 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): New >480 | 11 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): New >500 | 11 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): New >500 | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): New >480 | 9 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): Increase from baseline >30 | 8 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): New >450 | 5 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): Increase from baseline >60 | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): New >500 | 8 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | Heart rate (bpm): New <60 | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): Increase from baseline >60 | 5 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | Heart rate (bpm): New <60 | 0 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): New >450 | 4 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): New >480 | 4 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): New >500 | 2 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): Increase from baseline >30 | 4 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcB (msec): Increase from baseline >60 | 1 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): New >450 | 2 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): New >480 | 3 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): New >500 | 4 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): Increase from baseline >30 | 4 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QTcF (msec): Increase from baseline >60 | 0 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): New >450 | 4 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): New >480 | 1 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): New >500 | 1 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): Increase from baseline >30 | 3 Participants |
| Placebo | Number of Participants According to Categorization of Electrocardiogram (ECG) Data | QT (msec): Increase from baseline >60 | 0 Participants |
Secondary
Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias
Arrhythmia assessment: incidence of new and clinically significant ventricular or atrial arrhythmias was assessed by an implantable cardioverter defibrillator (ICD) or CRT defibrillator (CRT-D) applicable device interrogations.
Time frame: Baseline, Week 12, Week 24
Population: The SAS included all participants who received at least 1 dose of study intervention regardless of NYHA functional class. Here, Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07265803 (ARRY-371797) | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Baseline: Clinically significant atrial arrhythmia | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 12: Clinically significant atrial arrhythmia | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 24: Clinically significant atrial arrhythmia | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Baseline: Clinically significant ventricular arrhythmia | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 12: Clinically significant ventricular arrhythmia | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 24: Clinically significant ventricular arrhythmia | 0 Participants |
| Placebo | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 12: Clinically significant ventricular arrhythmia | 3 Participants |
| Placebo | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Baseline: Clinically significant atrial arrhythmia | 0 Participants |
| Placebo | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Baseline: Clinically significant ventricular arrhythmia | 0 Participants |
| Placebo | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 12: Clinically significant atrial arrhythmia | 2 Participants |
| Placebo | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 24: Clinically significant ventricular arrhythmia | 0 Participants |
| Placebo | Number of Participants With a New Clinically Significant Ventricular or Atrial Arrhythmias | Week 24: Clinically significant atrial arrhythmia | 0 Participants |
Secondary
Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24
PGI-C is a global index that rate the severity of the disease using a 7-point scale. In this outcome the number participants with improvements in their heart failure symptoms and in their physical activity limitations?, were reported. Measured by the scale of: very much better, moderately better, a little better, no change, a little worse, moderately worse, very much worse (listed from better to worse).
Time frame: Week 12, Week 24
Population: EAS included all NYHA functional Class II or III randomized participants. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Very Much Better | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | A Little Worse | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Moderately Better | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Moderately Better | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | A Little Better | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Moderately Better | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | No Change | 24 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | A Little Better | 7 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | A Little Worse | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Moderately Worse | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Moderately Worse | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | No Change | 16 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Very Much Worse | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | No Change | 18 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Very Much Better | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | A Little Worse | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Moderately Better | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Very Much Worse | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | A Little Better | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Moderately Worse | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | No Change | 19 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | A Little Better | 7 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | A Little Worse | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Very Much Worse | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Moderately Worse | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Very Much Better | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Very Much Worse | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Very Much Better | 0 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Very Much Worse | 0 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Very Much Better | 2 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Moderately Better | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | A Little Better | 9 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | No Change | 17 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | A Little Worse | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Moderately Worse | 0 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in heart failure symptoms | Very Much Worse | 2 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Very Much Better | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Moderately Better | 2 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | A Little Better | 6 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | No Change | 16 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | A Little Worse | 2 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Moderately Worse | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in heart failure symptoms | Very Much Worse | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Very Much Better | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Moderately Better | 2 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | A Little Better | 5 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | No Change | 21 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | A Little Worse | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Moderately Worse | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 12: Overall change in physical activity limitations | Very Much Worse | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Very Much Better | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Moderately Better | 0 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | A Little Better | 4 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | No Change | 20 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | A Little Worse | 3 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Change (PGI-C) Score at Weeks 12 and 24 | Week 24: Overall change in physical activity limitations | Moderately Worse | 1 Participants |
Secondary
Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24
PGI-S is a global index that rate the severity of the disease using a 5-point scale. In this outcome the number of participants with improvements in PGI-S the severity of their heart failure symptoms and in the severity of their PL were reported. Measured by the scale of: none, mild, moderate, severe or very severe (listed from better to worse).
Time frame: Week 12, Week 24
Population: EAS included all NYHA functional Class II or III randomized participants. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Number Analyzed signifies number of participants evaluable for specified rows of respective arms.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Very Severe | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | None | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Mild | 16 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Moderate | 8 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Severe | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Very Severe | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | None | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Mild | 11 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Moderate | 10 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Severe | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | None | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Mild | 11 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Moderate | 12 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Severe | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Very Severe | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | None | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Mild | 5 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Moderate | 13 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Severe | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Very Severe | 0 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Moderate | 15 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Very Severe | 0 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | None | 7 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | None | 5 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | None | 6 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Mild | 14 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Mild | 5 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Moderate | 10 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Very Severe | 0 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Severe | 2 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Moderate | 15 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of heart failure symptoms | Very Severe | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Mild | 7 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | None | 6 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Severe | 4 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Mild | 10 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of physical activity limitations | Severe | 3 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Moderate | 12 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 12: Severity of physical activity limitations | Very Severe | 1 Participants |
| Placebo | Number of Participants With Improvement From Baseline in Patient Global Impression of Severity (PGI-S) Score at Weeks 12 and 24 | Week 24: Severity of heart failure symptoms | Severe | 3 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Following parameters were analyzed for laboratory examination: hematology (eosinophils, erythrocytes, hemoglobin, hematocrit, granulocytes, leukocytes, lymphocytes, monocytes, platelets, neutrophils, nucleated erythrocytes); blood chemistry (alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bicarbonate, bilirubin, blood urea nitrogen, C-reactive protein, calcium, chloride, creatinine, creatine kinase, epidermal growth factor receptor, follicle stimulating hormone, gamma glutamyl transferase, glucose, magnesium, N-Terminal ProB-type natriuretic peptide, phosphate, potassium, protein, sodium, potassium, thyrotropin, troponin I, troponin T, urate).
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Population: The SAS included all participants who received at least 1 dose of study intervention regardless of NYHA functional class.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocytes: Low (Males: < 4.63, Females: <3.7) 10^12/L | 14 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Alkaline Phosphatase: LOW (Males: < 43; Females: <30) U/L | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Eosinophils: High (>0.8) 10^9/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Alkaline Phosphatase: HIGH (> 115) U/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Lymphocytes: Low (< 0.9) 10^9/L | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Aspartate Aminotransferase: HIGH (Males: > 43; Females: > 36) U/L | 11 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocytes: High (Males: > 6.08, Females: > 5.2) 10^12/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Bicarbonate: LOW (< 21) mmol/L | 9 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Lymphocytes: Low (> 3.6) 10^9/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Bicarbonate: HIGH (> 33) mmol/L | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Hemoglobin: Low (<27) pg | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Blood Urea Nitrogen: HIGH (> 7.14) mmol/L | 28 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Lymphocytes/Leukocytes: Low (< 12) % | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Calcium: LOW (< 2.12) mmol/L | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocytes Distribution Width: High (>14.5) % | 22 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Calcium: HIGH (> 2.62) mmol/L | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Lymphocytes/Leukocytes: High (> 46) % | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Chloride: LOW (< 95) mmol/L | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | C Reactive Protein: HIGH (> 47.6) nmol/L | 20 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Creatine Kinase: LOW (< 24) U/L | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Mean Platelet Volume: Low (< 9.6) fL | 5 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Creatine Kinase: HIGH (Males: > 207; Females: > 169) U/L | 20 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Hematocrit: Low (Males: <0.37, Females: <0.33) L/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Creatinine: LOW (< 62) mcmol/L | 14 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Mean Platelet Volume: High (> 13.8) fL | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Creatinine: HIGH (> 124) mcmol/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Hemoglobin: High (>34) pg | 0 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Creatinine Clearance: LOW (Males: < 85; Females: <75) mL/min | 9 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Monocytes: High (> 1.2) 10^9/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Creatinine Clearance: HIGH (Males: > 125; Females: > 115) mL/min | 16 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Hematocrit: High (Males: >0.51, Females: >0.47) L/L | 12 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Direct Bilirubin: HIGH (> 6.8) mcmol/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Monocytes/Leukocytes: High (>11) % | 11 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Epidermal Growth Factor Receptor: LOW (Males: < 60) mL/min/1.73m2 | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Eosinophils/Leukocytes: High (>7) % | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Follicle Stimulating Hormone: HIGH (Males: > 12.4; Females: > 21.5) IU/L | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Neutrophils: LOW (< 1.7) 10^9/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase: LOW (Males: < 10; Females: <5) U/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Hemoglobin: Low (Males: < 125; Females: <110) g/L | 7 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase: HIGH (Males: > 49; Females: > 32) U/L | 15 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Neutrophils: HIGH (> 7.9) 10^9/L | 8 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Glucose: LOW (Males < 3.94, Females < 3.33) mmol/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Volume: Low (Males <78, Females <82) | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Glucose: HIGH (Males > 7.66, Females > 6.38) mmol/L | 10 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Neutrophils/Leukocytes: HIGH (> 71) % | 16 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Magnesium: HIGH (> 1.05) mmol/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Hemoglobin: High (Males: > 170; Females: > 155) g/L | 5 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | N-Terminal ProB-type Natriuretic Peptide: HIGH (> 14.63) pmol/L | 40 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Nucleated Erythrocytes: HIGH (> 0.01) 10^9/L | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Phosphate: LOW (< 0.81) mmol/L | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Bilirubin: HIGH (> 18.8) mcmol/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Phosphate: HIGH (> 1.45) mmol/L | 8 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Nucleated Erythrocytes/Leukocytes: HIGH (> 0.2) % | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Potassium: LOW (< 3.5) mmol/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Immature Granulocytes: High (> 0.07) 10^9/L | 9 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Potassium: HIGH (> 5) mmol/L | 7 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Platelets: LOW (< 163) 10^9/L | 13 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Protein: LOW (< 60) g/L | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Volume: High (Males >100, Females >102) | 10 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Protein: High (> 80) g/L | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Platelets: HIGH (> 375) 10^9/L | 2 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Sodium: HIGH (> 145) mmol/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Immature Granulocytes/Leukocytes: High (> 1) % | 6 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Thyrotropin: LOW (< 0.27) mIU/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Alanine Aminotransferase: LOW (< 10) U/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Thyrotropin: HIGH (> 4.2) mIU/L | 5 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Hemoglobin Concentration: Low (<310) g/L | 30 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Troponin I: HIGH (> 0.3) mcg/L | 4 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Alanine Aminotransferase: HIGH (Males: > 40; Females: > 33) U/L | 18 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Troponin T: HIGH (> 14) ng/L | 36 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Leukocytes: Low (< 3.7) 10^9/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Urate: LOW (Males: < 0.238; Females: <0.119) mmol/L | 3 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Albumin: LOW (< 35) g/L | 1 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Urate: HIGH (Males: > 0.476; Females: > 0.357) mmol/L | 9 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Laboratory Test Abnormalities | Leukocytes: High (> 11) 10^9/L | 9 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Urate: HIGH (Males: > 0.476; Females: > 0.357) mmol/L | 17 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Bilirubin: HIGH (> 18.8) mcmol/L | 12 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | C Reactive Protein: HIGH (> 47.6) nmol/L | 19 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Eosinophils: High (>0.8) 10^9/L | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Eosinophils/Leukocytes: High (>7) % | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Hemoglobin Concentration: Low (<310) g/L | 29 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Hemoglobin: Low (<27) pg | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Hemoglobin: High (>34) pg | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Volume: Low (Males <78, Females <82) | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocyte Mean Corpuscular Volume: High (Males >100, Females >102) | 15 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocytes: Low (Males: < 4.63, Females: <3.7) 10^12/L | 16 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocytes: High (Males: > 6.08, Females: > 5.2) 10^12/L | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Erythrocytes Distribution Width: High (>14.5) % | 20 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Hematocrit: Low (Males: <0.37, Females: <0.33) L/L | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Hematocrit: High (Males: >0.51, Females: >0.47) L/L | 15 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Hemoglobin: Low (Males: < 125; Females: <110) g/L | 5 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Hemoglobin: High (Males: > 170; Females: > 155) g/L | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Immature Granulocytes: High (> 0.07) 10^9/L | 7 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Immature Granulocytes/Leukocytes: High (> 1) % | 6 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Leukocytes: Low (< 3.7) 10^9/L | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Leukocytes: High (> 11) 10^9/L | 8 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Lymphocytes: Low (< 0.9) 10^9/L | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Lymphocytes: Low (> 3.6) 10^9/L | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Lymphocytes/Leukocytes: Low (< 12) % | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Lymphocytes/Leukocytes: High (> 46) % | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Mean Platelet Volume: Low (< 9.6) fL | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Mean Platelet Volume: High (> 13.8) fL | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Monocytes: High (> 1.2) 10^9/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Monocytes/Leukocytes: High (>11) % | 10 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Neutrophils: LOW (< 1.7) 10^9/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Neutrophils: HIGH (> 7.9) 10^9/L | 5 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Neutrophils/Leukocytes: HIGH (> 71) % | 17 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Nucleated Erythrocytes: HIGH (> 0.01) 10^9/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Nucleated Erythrocytes/Leukocytes: HIGH (> 0.2) % | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Platelets: LOW (< 163) 10^9/L | 11 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Platelets: HIGH (> 375) 10^9/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Alanine Aminotransferase: LOW (< 10) U/L | 5 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Alanine Aminotransferase: HIGH (Males: > 40; Females: > 33) U/L | 17 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Albumin: LOW (< 35) g/L | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Alkaline Phosphatase: LOW (Males: < 43; Females: <30) U/L | 5 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Alkaline Phosphatase: HIGH (> 115) U/L | 5 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Aspartate Aminotransferase: HIGH (Males: > 43; Females: > 36) U/L | 8 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Bicarbonate: LOW (< 21) mmol/L | 12 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Bicarbonate: HIGH (> 33) mmol/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Blood Urea Nitrogen: HIGH (> 7.14) mmol/L | 27 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Calcium: LOW (< 2.12) mmol/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Calcium: HIGH (> 2.62) mmol/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Chloride: LOW (< 95) mmol/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Creatine Kinase: LOW (< 24) U/L | 2 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Creatine Kinase: HIGH (Males: > 207; Females: > 169) U/L | 12 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Creatinine: LOW (< 62) mcmol/L | 13 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Creatinine: HIGH (> 124) mcmol/L | 6 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Creatinine Clearance: LOW (Males: < 85; Females: <75) mL/min | 8 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Creatinine Clearance: HIGH (Males: > 125; Females: > 115) mL/min | 14 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Direct Bilirubin: HIGH (> 6.8) mcmol/L | 8 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Epidermal Growth Factor Receptor: LOW (Males: < 60) mL/min/1.73m2 | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Follicle Stimulating Hormone: HIGH (Males: > 12.4; Females: > 21.5) IU/L | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase: LOW (Males: < 10; Females: <5) U/L | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Gamma Glutamyl Transferase: HIGH (Males: > 49; Females: > 32) U/L | 27 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Glucose: LOW (Males < 3.94, Females < 3.33) mmol/L | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Glucose: HIGH (Males > 7.66, Females > 6.38) mmol/L | 10 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Magnesium: HIGH (> 1.05) mmol/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | N-Terminal ProB-type Natriuretic Peptide: HIGH (> 14.63) pmol/L | 37 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Phosphate: LOW (< 0.81) mmol/L | 6 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Phosphate: HIGH (> 1.45) mmol/L | 4 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Potassium: LOW (< 3.5) mmol/L | 0 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Potassium: HIGH (> 5) mmol/L | 16 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Protein: LOW (< 60) g/L | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Protein: High (> 80) g/L | 3 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Sodium: HIGH (> 145) mmol/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Thyrotropin: LOW (< 0.27) mIU/L | 1 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Thyrotropin: HIGH (> 4.2) mIU/L | 5 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Troponin I: HIGH (> 0.3) mcg/L | 6 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Troponin T: HIGH (> 14) ng/L | 34 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | Urate: LOW (Males: < 0.238; Females: <0.119) mmol/L | 2 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity
An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and all Non-SAEs. Grade \>=3 AEs meant severe AEs.
Time frame: Maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Population: The SAS included all participants who received at least 1 dose of study intervention regardless of NYHA functional class.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07265803 (ARRY-371797) | Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity | Participants with TEAEs | 35 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity | Participants with serious TEAEs | 10 Participants |
| PF-07265803 (ARRY-371797) | Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity | Participants with severe (Grades >=3) TEAEs | 16 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity | Participants with TEAEs | 34 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity | Participants with serious TEAEs | 21 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and by Severity | Participants with severe (Grades >=3) TEAEs | 20 Participants |
Secondary
Overall Survival (OS)
OS was defined as time from randomization to death due to any cause. Participants who did not have a death date were censored for OS at their last contact date. Kaplan-Meier method and cox regression model were used for analysis.
Time frame: From randomization up to death due to any cause or censored date, maximum up to 212.28 weeks (maximum exposure was of 208 weeks)
Population: The SAS included all participants who received at least 1 dose of study intervention regardless of NYHA functional class.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-07265803 (ARRY-371797) | Overall Survival (OS) | NA Weeks |
| Placebo | Overall Survival (OS) | NA Weeks |
p-value: 0.83795% CI: [0.3, 4.63]Log Rank