Heart Failure
Conditions
Keywords
Heart Failure with mildly reduced ejection, Heart Failure with preserved ejection fraction
Brief summary
The purpose of this study is to learn about the safety and effects of the study medicine (PF-07328948) for the possible treatment of heart failure (HF).
Detailed description
All participants in this study will take either the study medicine (PF-07328948) tablets, or placebo tablets, once daily, by mouth, every day for 36 weeks. The study determines if the study medicine (PF-07328948) is safe and effective compared to placebo in people with heart failure who are already taking standard-of-care medications for heart failure that include sodium-glucose cotransporter 2 (SGLT2) inhibitors. Participants will be involved in this study for about 48 weeks. During this time, participants will visit the study clinic 15 times. In general, 5 of these visits may be performed at home by phone and the other 10 visits will take place at the study site.
Interventions
DRUGPlacebo
ARM 1
DRUGLow Dose PF-07328948
ARM 2
DRUGMedium Dose PF-07328948
ARM 3
DRUGHigh Dose PF-07328948
ARM 4
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind, placebo-controlled study
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
This study is seeking participants who are: Key Inclusion Criteria include: * aged 18 years to \< 80 years * clinically confirmed to have a diagnosis of heart failure for at least 3 months * New York Heart Association Class II-IV symptoms * left ventricular ejection fraction greater than 40% * Kansas City Cardiomyopathy Questionnaire-23 Total Symptom Score \< 85 * Six-minute walking distance greater than 75 meters Key
Exclusion criteria
include: * Type 1 diabetes mellitus, liver cirrhosis or any condition that can possibly affect how the medicine is absorbed into the body. * Major surgery scheduled for the duration of the study, affecting walking ability in the opinion of the study doctor. * History of heart transplantation, or currently listed for a heart transplant, or current planned use of IV vasodilators and/ or inotropes * Prior intolerance/known hypersensitivity to an SGLT2 inhibitor or contraindication to an SGLT2 inhibitor
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Clinical Events | over 36 weeks | Adjudicated cardiovascular death and worsening heart failure events through 36 weeks. |
| Change From Baseline in 6-Minute Walk Test (6MWD) | Baseline, week 36 post-dose | A submaximal exercise test that measures the distance the participant can walk within prescribed time of 6 minutes. Participants are asked to perform the test at a pace comfortable to them with as many breaks as needed. The total distance walked is recorded. |
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Total Symptom Score (KCCQ-23 TSS) | Baseline, week 36 | KCCQ is a 23-item heart-failure specific questionnaire quantified into the following scores: symptom frequency, symptom burden, symptom stability, physical limitations, social limitations, quality of life, and self-efficacy, total symptom score, overall summary score, and clinical summary score. To facilitate interpretation, all scores are presented on a scale of 0 to 100 points, with lower scores indicating more severe symptoms and/or limitations, and a score of 100 indicating no symptoms, no limitations, and excellent quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Baseline, up to week 40 | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE that, at any dose, results in 1 or more 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. Treatment-emergent are events between first dose of study drug and up to Week 40 that were absent before treatment or that worsened relative to pre-treatment state. AEs include both serious and non-serious adverse events. |
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall Symptom Score (KCCQ-23 TSS) and physical limitation in participants taking PF-07328948 vs. placebo on HF disease-specific health status related to HFmrEF/HFpEF. | Baseline, week 36 | KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: Physical limitation, Social limitation, Quality of life, Self-efficacy, Symptom stability, Symptom frequency, Symptom burden, and Total symptoms (calculated as the mean of Symptom frequency and Symptom burden scores). Two summary scores are also calculated: Clinical Summary (calculated as mean of Physical limitation and Total symptom scores) and Overall Summary (calculated as mean of Physical limitation, Social limitation, Total symptoms, and Quality of life scores). Domain and summary scores were scaled to range from 0 (minimum) to 100 (maximum); higher scores represent better health status. |
| Change From Baseline in 6-minute walk test distance (6MWD) in participants taking PF-07328948 vs. placebo on HF disease-specific health status related to HFmrEF/HFpEF. | Baseline, week 36 | A submaximal exercise test that measures the distance the participant can walk within prescribed time of 6 minutes. Participants are asked to perform the test at a pace comfortable to them with as many breaks as needed. The total distance walked is recorded. |
| CPET Substudy) : Change From Baseline in Peak Oxygen Consumption (pVO2) at Week 36 | Baseline, Week 36 | Cardiopulmonary exercise testing |
| Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP) Concentration at Week 36 | Baseline, Week 36 | NT-proBNP is a biomarker of cardiac stress (myocardial necrosis and increased filling pressures/ LV wall stress). |
| Change From Baseline in Kansas City Cardiomyopathy Questionnaire Overall clinical symptom Score (KCCQ-23 CSS) and physical limitation) in participants taking PF-07328948 vs. placebo on HF disease-specific health status related to HFmrEF/HFpEF. | Baseline, week 36 | KCCQ is a 23-item participant-completed questionnaire that assesses health status and health-related quality of life in participants with heart failure. Eight domain scores were calculated for the KCCQ: Physical limitation, Social limitation, Quality of life, Self-efficacy, Symptom stability, Symptom frequency, Symptom burden, and Total symptoms (calculated as the mean of Symptom frequency and Symptom burden scores). Two summary scores are also calculated: Clinical Summary (calculated as mean of Physical limitation and Total symptom scores) and Overall Summary (calculated as mean of Physical limitation, social limitation, Total symptoms, and Quality of life scores). Domain and summary scores were scaled to range from 0 (minimum) to 100 (maximum); higher scores represent better health status. |
Countries
Brazil, Bulgaria, Canada, China, Czechia, France, Hungary, Japan, Poland, Puerto Rico, Spain, United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed