Heart Enlargement, Heart Failure, Myocardial Infarction
Conditions
Brief summary
The main purpose of the study is to test whether a possible new drug (called PG-116800) can prevent some of the damage to heart muscle in patients who have had a heart attack. The study will also supply information regarding possible uses of this compound in cardiovascular disease.
Detailed description
Heart attacks cause damage to heart muscle that can weaken the heart and lead to changes in the shape and pumping ability of the heart. These changes can lead to heart failure. An enzyme called metalloproteinase (MMP) plays a role in this damage. The main purpose of the study is to test whether a possible new drug (called PG-116800) that interferes with the MMP enzyme can prevent some of the damage to heart muscle in patients who have had a heart attack. The study will also supply information regarding possible uses of this compound in cardiovascular disease. This is a Phase II proof-of-concept study; that is, it is a first attempt to treat sick people with the drug to see if it works. The study is interventional since we will be using a drug to interfere with the heart tissue damage that follows a heart attack.
Interventions
DRUGPG-116800 (given as PG-530742)
200 mg tablet of PG-116800 (given as PG-530742)twice a day for 90 days
DRUGPlacebo tablet
placebo tablet, twice a day for 90 days
Sponsors
Procter and Gamble
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: * Be at least 18 years of age but not older than 80 years of age at screening; * Be diagnosed with a heart attack based on electrocardiogram (ECG) and cardiac enzymes criteria; * The qualifying heart attack has to be a first heart attack; * The qualifying heart attack has to result in a left ventricular ejection fraction (a measure of the working efficiency of the heart) between 15% and 40%. Exclusion: * Documented previous history of heart attack; * Any past history of heart failure; * Hemodynamic instability (no instability of circulatory system); * History of congenital heart disease and cardiomyopathy (weakened heart muscle) associated with connective tissue disorders; * Recent history or current moderate-to-severe kidney or liver impairment; * Significant blood dyscrasias (disorders of the blood cells); * Females who are currently: pregnant; breast-feeding; or are of childbearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi in mL/m2) at Day 90 Post Myocardial Infarction (MI) | 90 days | Mean change of left ventricular end diastolic volume index (mL/m2) as evaluated via ventricular end-diastolic volume index augmentation 90 days post Myocardial Infarction (MI) |
Countries
Canada, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo tablet twice daily for 90 days | 128 |
| PG-116800 Tablet PG-116800 tablet (200 mg) twice daily for 90 days | 125 |
| Total | 253 |
Baseline characteristics
| Characteristic | PG-116800 Tablet | Total | Placebo |
|---|---|---|---|
| Age Continuous | 59.7 years STANDARD_DEVIATION 11.71 | 59.8 years STANDARD_DEVIATION 10.96 | 59.9 years STANDARD_DEVIATION 10.22 |
| Region of Enrollment Canada | 23 participants | 45 participants | 22 participants |
| Region of Enrollment Poland | 86 participants | 173 participants | 87 participants |
| Region of Enrollment United States | 16 participants | 35 participants | 19 participants |
| Sex: Female, Male Female | 32 Participants | 66 Participants | 34 Participants |
| Sex: Female, Male Male | 93 Participants | 187 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 124 / 128 | 124 / 125 |
| serious Total, serious adverse events | 67 / 128 | 75 / 125 |
Outcome results
Primary
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi in mL/m2) at Day 90 Post Myocardial Infarction (MI)
Mean change of left ventricular end diastolic volume index (mL/m2) as evaluated via ventricular end-diastolic volume index augmentation 90 days post Myocardial Infarction (MI)
Time frame: 90 days
Population: A patient was considered evaluable for the primary efficacy assessment if data were complete for at least the baseline and Day 90 visit (i.e., no data were imputed for the primary endpoint).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi in mL/m2) at Day 90 Post Myocardial Infarction (MI) | 5.48 mL/m2 | Standard Error 1.41 |
| PG-116800 Tablet | Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi in mL/m2) at Day 90 Post Myocardial Infarction (MI) | 5.09 mL/m2 | Standard Error 1.45 |
Comparison: Changes from baseline in efficacy parameters at Day 90.p-value: 0.4239ANOVA