Hypercholesterolemia, Atherosclerotic Cardiovascular Diseases
Conditions
Keywords
hyperlipidemia, cholesterol, heterozygous familial hypercholesterolemia, atherosclerotic cardiovascular disease, ASCVD, HeFH, LDL
Brief summary
The purpose of this study is to see if ETC-1002 (bempedoic acid) is safe and well-tolerated versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol that is not adequately controlled by their current therapy.
Interventions
DRUGETC-1002
ETC-1002 180 mg tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)
DRUGPlacebo
Matching placebo tablets taken orally, once per day. Patients remain on ongoing statin therapy (not study provided)
Sponsors
Esperion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Fasting LDL-C ≥ 70 mg/dL * High cardiovascular risk (diagnosis of HeFH or ASCVD) * Be on maximally tolerated lipid-modifying therapy
Exclusion criteria
* Total fasting triglyceride ≥500 mg/dL * Renal dysfunction or nephrotic syndrome or history of nephritis * Body Mass Index (BMI) ≥50kg/m2 * Significant cardiovascular disease or cardiovascular event in the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 52 weeks | TEAEs, defined as adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. |
| Change From Baseline to Week 52 in Hemoglobin Level | Baseline and Week 52 | Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels. |
| Change From Baseline to Week 52 in Creatinine Level | Baseline and Week 52 | Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels. |
| Change From Baseline to Week 52 in Uric Acid (Urate) Level | Baseline and Week 52 | Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels. |
| Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Up to approximately 52 weeks | Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to renal events were assessed using the following preferred terms: renal failure, renal impairment, acute kidney injury (system organ class: renal and urinary disorders); blood creatinine increased, glomerular filtration rate decreased, blood urea increased, estimated glomerular filtration rate (eGFR) \<30 milliliter per minute per 1.73 square meter (ml/min/1.73m\^2), and change from baseline in creatinine \>1 mg/dL (system organ class: investigations); and gout (system organ class: metabolism and nutrition disorders). The percentage of unique participants is reported in the Overall renal disorder AESIs category; a participant could have been represented in more than one of the individual renal disorder AESIs. |
| Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Up to approximately 52 weeks | Treatment-emergent AESIs were predefined and monitored throughout the study. New onset or worsening diabetes was assessed using the following preferred terms: type 2 diabetes mellitus, diabetes mellitus, hyperglycaemia, glucose tolerance impaired, diabetes mellitus inadequate control, and impaired fasting glucose (system organ class: metabolism and nutrition disorders); blood glucose increased, glycosylated haemoglobin increased, blood glucose abnormal, and glucose urine present (system organ class: investigations); and glycosuria (system organ class: renal and urinary disorders). The percentage of unique participants is reported in the Overall new onset/worsening diabetes mellitus AESIs category; a participant could have been represented in more than one of the individual new onset/worsening diabetes mellitus AESIs. |
| Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Up to approximately 52 weeks | Treatment-emergent AESIs were predefined and monitored throughout the study. Neurocognitive disorder was assessed using the following preferred terms: memory impairment, amnesia, and cognitive disorder (system organ class: nervous system disorders); confusional state and disorientation (system organ class: psychiatric disorders). The percentage of unique participants is reported in the Overall neurocognitive disorder AESIs category; a participant could have been represented in more than one of the individual neurocognitive disorder AESIs. |
| Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Up to approximately 52 weeks | Treatment-emergent AESIs were predefined and monitored throughout the study. Muscular safety was assessed using the following preferred terms and laboratory abnormalities: myalgia, muscle spasms, pain in extremity, muscular weakness (system organ class: musculoskeletal and connective tissue disorders), and creatine kinase \>5 ULN (repeated and confirmed). The percentage of unique participants is reported in the Overall muscular disorder AESIs category; a participant could have been represented in more than one of the individual muscular disorder AESIs. |
| Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis | Up to approximately 52 weeks | Treatment-emergent AESIs were predefined and monitored throughout the study. Metabolic acidosis was assessed using the preferred term metabolic acidosis (system organ class: metabolism and nutrition disorders). |
| Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Up to approximately 52 weeks | Treatment-emergent AESIs were predefined and monitored throughout the study. Hypoglycemia was assessed using the following preferred terms: hypoglycaemia (system organ class: metabolism and nutrition disorders); blood glucose abnormal and blood glucose decreased (system organ class: investigations). The percentage of unique participants is reported in the Overall hypoglycemia AESIs category; a participant could have been represented in more than one of the individual hypoglycemia AESIs. |
| Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Up to approximately 52 weeks | Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to hepatic events were assessed using the following preferred terms and laboratory abnormalities: aspartate aminotransferase (AST) increased, Alanine aminotransferase (ALT) increased, Hepatic enzyme increased, Blood bilirubin increased, liver function test (LFT) abnormal, LFT increased, hepatic enzyme abnormal, transaminases increased, potential Hy's Law cases (PHLC) \[AST and (&)/or ALT \>3 x upper limit of normal (ULN) with concurrent total bilirubin \>2 x ULN\], AST and/or ALT \>3 x ULN, and total bilirubin \>2 x ULN (system organ class: investigations). AST and ALT values were repeated and confirmed. Repeated and confirmed was defined as a participant having the last on-study LFT \> x ULN, the last on-treatment LFT \> x ULN, or LFT \> x ULN followed by another LFT \> x ULN. |
| Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations | Up to approximately 52 weeks | TEAEs of special interest (AESIs) were predefined and monitored throughout the study. Creatine kinase elevations were assessed using the following preferred term: Blood creatine phosphokinase increased (system organ class: investigations). |
| Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Up to approximately 52 weeks | TEAEs, defined as AEs that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. Cardiovascular events were considered as adverse events of special interest. Treatment-emergent = TE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | Baseline; Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(LDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Least Square mean= LS mean. Percent change was analyzed using the analysis of covariance (ANCOVA) method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Absolute Change From Baseline to Week 12 in LDL-C | Baseline; Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Absolute change from baseline was calculated as: LDL-C value at Week 12 minus Baseline value. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 24 in LDL-C | Baseline; Week 24 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(LDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | Baseline; Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(non-HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Percent Change From Baseline to Week 52 in hsCRP | Baseline; Week 52 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(hsCRP value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Percent Change From Baseline to Week 24 in hsCRP | Baseline; Week 24 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(hsCRP value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Percent Change From Baseline to Week 52 in apoB | Baseline; Week 52 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(apoB value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Percent Change From Baseline to Week 24 in apoB | Baseline; Week 24 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(apoB value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed |
| Percent Change From Baseline to Week 52 in TC | Baseline; Week 52 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(TC value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Percent Change From Baseline to Week 24 in TC | Baseline; Week 24 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(TC value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Percent Change From Baseline to Week 52 in Non-HDL-C | Baseline; Week 52 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(non-HDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Percent Change From Baseline to Week 24 in Non-HDL-C | Baseline; Week 24 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(non-HDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. |
| Percent Change From Baseline to Week 52 in LDL-C | Baseline; Week 52 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(LDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | Baseline; Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) | Baseline; Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | Baseline; Week 12 | Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(TC value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate. |
| Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 | Week 12, Week 24, and Week 52 | The percentage of participants who achieved lowering in lipid values of LDL-C below 70 mg/dL have been reported. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Observed data was used for the analysis, no imputation for the missing data was performed. |
Countries
Canada, Germany, Netherlands, Poland, United Kingdom, United States
Participant flow
Recruitment details
A total of 2230 participants were randomized 2:1 to either bempedoic acid or placebo. One participant was randomized to bempedoic acid treatment, but never received any dose of investigational medicinal product (IMP) i.e. study drug.
Pre-assignment details
The study consisted of 2 periods: a 2-week screening period and a 52-week double-blind, randomized treatment period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo During the double-blind treatment period, participants received placebo tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | 742 |
| Bempedoic Acid During the double-blind treatment period, participants received bempedoic acid 180 mg tablet, once daily by mouth for 52 weeks. In addition, participants received stable background lipid-modifying therapy(ies) including a maximally tolerated statin throughout the study. | 1,488 |
| Total | 2,230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 37 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Sponsor decision | 0 | 1 |
| Overall Study | Withdrawal by participant | 23 | 40 |
Baseline characteristics
| Characteristic | Total | Bempedoic Acid | Placebo |
|---|---|---|---|
| Age, Continuous | 66.1 years STANDARD_DEVIATION 8.96 | 65.8 years STANDARD_DEVIATION 9.11 | 66.8 years STANDARD_DEVIATION 8.64 |
| Apolipoprotein B (apoB) | 87.9 mg/dL STANDARD_DEVIATION 21.66 | 88.5 mg/dL STANDARD_DEVIATION 21.57 | 86.8 mg/dL STANDARD_DEVIATION 21.82 |
| Baseline statin intensity High | 1112 Participants | 742 Participants | 370 Participants |
| Baseline statin intensity Low | 148 Participants | 100 Participants | 48 Participants |
| Baseline statin intensity Moderate | 970 Participants | 646 Participants | 324 Participants |
| Cardiovascular history: atherosclerotic cardiovascular disease (ASCVD) No | 54 Participants | 39 Participants | 15 Participants |
| Cardiovascular history: atherosclerotic cardiovascular disease (ASCVD) Yes | 2176 Participants | 1449 Participants | 727 Participants |
| Cardiovascular history: heterozygous familial hypercholesterolemia (HeFH) No | 2151 Participants | 1432 Participants | 719 Participants |
| Cardiovascular history: heterozygous familial hypercholesterolemia (HeFH) Yes | 79 Participants | 56 Participants | 23 Participants |
| Concomitant lipid-modifying therapy (LMT): Statin No | 3 Participants | 3 Participants | 0 Participants |
| Concomitant lipid-modifying therapy (LMT): Statin Yes | 2227 Participants | 1485 Participants | 742 Participants |
| Concomitant LMT: Ezetimibe No | 2058 Participants | 1372 Participants | 686 Participants |
| Concomitant LMT: Ezetimibe Yes | 172 Participants | 116 Participants | 56 Participants |
| Concomitant LMT: Fibrate No | 2150 Participants | 1434 Participants | 716 Participants |
| Concomitant LMT: Fibrate Yes | 80 Participants | 54 Participants | 26 Participants |
| Concomitant LMT: None Concomitant LMT: None | 2 Participants | 2 Participants | 0 Participants |
| Concomitant LMT: None Concomitant LMT: Yes | 2228 Participants | 1486 Participants | 742 Participants |
| Estimated glomerular filtration rate (eGFR) Mild Renal Impairment: 60-89 mL/min/1.73m^2 | 1414 Participants | 946 Participants | 468 Participants |
| Estimated glomerular filtration rate (eGFR) Moderate Renal Impairment: 30-59 mL/min/1.73m^2 | 329 Participants | 222 Participants | 107 Participants |
| Estimated glomerular filtration rate (eGFR) Normal: ≥ 90 mL/min/1.73m^2 | 487 Participants | 320 Participants | 167 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 24 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2195 Participants | 1464 Participants | 731 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| High-density lipoprotein cholesterol (HDL-C) | 48.90 mg/dL STANDARD_DEVIATION 11.752 | 48.71 mg/dL STANDARD_DEVIATION 11.853 | 49.29 mg/dL STANDARD_DEVIATION 11.545 |
| High-sensitivity C-reactive protein (hsCRP) | 1.49 mg/L | 1.49 mg/L | 1.51 mg/L |
| History of diabetes No | 1593 Participants | 1063 Participants | 530 Participants |
| History of diabetes Yes | 637 Participants | 425 Participants | 212 Participants |
| History of hypertension No | 462 Participants | 314 Participants | 148 Participants |
| History of hypertension Yes | 1768 Participants | 1174 Participants | 594 Participants |
| Low-density lipoprotein cholesterol (LDL-C) | 103.16 mg/dL STANDARD_DEVIATION 29.436 | 103.60 mg/dL STANDARD_DEVIATION 29.127 | 102.30 mg/dL STANDARD_DEVIATION 30.048 |
| Non-high-density lipoprotein cholesterol (non-HDL-C) | 130.41 mg/dL STANDARD_DEVIATION 33.737 | 130.92 mg/dL STANDARD_DEVIATION 33.677 | 129.37 mg/dL STANDARD_DEVIATION 33.855 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 14 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 57 Participants | 42 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 2139 Participants | 1423 Participants | 716 Participants |
| Sex: Female, Male Female | 602 Participants | 389 Participants | 213 Participants |
| Sex: Female, Male Male | 1628 Participants | 1099 Participants | 529 Participants |
| Total cholesterol (TC) | 179.32 mg/dL STANDARD_DEVIATION 35.306 | 179.66 mg/dL STANDARD_DEVIATION 35.143 | 178.64 mg/dL STANDARD_DEVIATION 35.645 |
| Triglycerides (TG) | 125.00 mg/dL | 126.25 mg/dL | 122.50 mg/dL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 1,487 | 2 / 742 |
| other Total, other adverse events | 792 / 1,487 | 381 / 742 |
| serious Total, serious adverse events | 216 / 1,487 | 104 / 742 |
Outcome results
Primary
Change From Baseline to Week 52 in Creatinine Level
Blood samples were drawn at defined time points during the course of the study to monitor creatinine levels.
Time frame: Baseline and Week 52
Population: Safety Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 52 in Creatinine Level | Baseline | 0.96 mg/dL | Standard Deviation 0.22 |
| Placebo | Change From Baseline to Week 52 in Creatinine Level | Change from Baseline at Week 52 | -0.02 mg/dL | Standard Deviation 0.12 |
| Bempedoic Acid | Change From Baseline to Week 52 in Creatinine Level | Baseline | 0.97 mg/dL | Standard Deviation 0.22 |
| Bempedoic Acid | Change From Baseline to Week 52 in Creatinine Level | Change from Baseline at Week 52 | 0.02 mg/dL | Standard Deviation 0.13 |
Primary
Change From Baseline to Week 52 in Hemoglobin Level
Blood samples were drawn at defined time points during the course of the study to monitor hemoglobin levels.
Time frame: Baseline and Week 52
Population: Safety Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 52 in Hemoglobin Level | Baseline | 14.07 grams per deciliter (g/dL) | Standard Deviation 1.26 |
| Placebo | Change From Baseline to Week 52 in Hemoglobin Level | Change from Baseline at Week 52 | -0.23 grams per deciliter (g/dL) | Standard Deviation 0.85 |
| Bempedoic Acid | Change From Baseline to Week 52 in Hemoglobin Level | Baseline | 14.22 grams per deciliter (g/dL) | Standard Deviation 1.26 |
| Bempedoic Acid | Change From Baseline to Week 52 in Hemoglobin Level | Change from Baseline at Week 52 | -0.58 grams per deciliter (g/dL) | Standard Deviation 0.88 |
Primary
Change From Baseline to Week 52 in Uric Acid (Urate) Level
Blood samples were drawn at defined time points during the course of the study to monitor uric acid (urate) levels.
Time frame: Baseline and Week 52
Population: Safety Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 52 in Uric Acid (Urate) Level | Change from Baseline at Week 52 | -0.06 milligrams per deciliter (mg/dL) | Standard Deviation 0.87 |
| Placebo | Change From Baseline to Week 52 in Uric Acid (Urate) Level | Baseline | 5.96 milligrams per deciliter (mg/dL) | Standard Deviation 1.35 |
| Bempedoic Acid | Change From Baseline to Week 52 in Uric Acid (Urate) Level | Baseline | 6.06 milligrams per deciliter (mg/dL) | Standard Deviation 1.37 |
| Bempedoic Acid | Change From Baseline to Week 52 in Uric Acid (Urate) Level | Change from Baseline at Week 52 | 0.73 milligrams per deciliter (mg/dL) | Standard Deviation 1.11 |
Primary
Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event
TEAEs, defined as AEs that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported. Cardiovascular events were considered as adverse events of special interest. Treatment-emergent = TE.
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any TE death from cardiovascular causes | 0.1 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any hospitalization for unstable angina | 1.5 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any nonfatal stroke | 0.3 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | TE death from noncardiovascular causes | 0.1 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any nonfatal myocardial infarction | 1.8 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Noncoronary arterial revascularization | 0.8 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any coronary revascularization | 3.2 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Hospitalization for heart failure | 0.1 percentage of participants |
| Placebo | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any adjudicated major clinical event | 5.7 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Hospitalization for heart failure | 0.6 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any adjudicated major clinical event | 4.6 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any TE death from cardiovascular causes | 0.4 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any nonfatal myocardial infarction | 1.3 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any nonfatal stroke | 0.3 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any coronary revascularization | 2.6 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Any hospitalization for unstable angina | 0.9 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | TE death from noncardiovascular causes | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Adjudicated Major Adverse Cardiovascular Event | Noncoronary arterial revascularization | 0.3 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations
TEAEs of special interest (AESIs) were predefined and monitored throughout the study. Creatine kinase elevations were assessed using the following preferred term: Blood creatine phosphokinase increased (system organ class: investigations).
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations | 1.8 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Creatine Kinase Elevations | 2.4 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders
Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to hepatic events were assessed using the following preferred terms and laboratory abnormalities: aspartate aminotransferase (AST) increased, Alanine aminotransferase (ALT) increased, Hepatic enzyme increased, Blood bilirubin increased, liver function test (LFT) abnormal, LFT increased, hepatic enzyme abnormal, transaminases increased, potential Hy's Law cases (PHLC) \[AST and (&)/or ALT \>3 x upper limit of normal (ULN) with concurrent total bilirubin \>2 x ULN\], AST and/or ALT \>3 x ULN, and total bilirubin \>2 x ULN (system organ class: investigations). AST and ALT values were repeated and confirmed. Repeated and confirmed was defined as a participant having the last on-study LFT \> x ULN, the last on-treatment LFT \> x ULN, or LFT \> x ULN followed by another LFT \> x ULN.
Time frame: Up to approximately 52 weeks
Population: Safety Population. The percentage of unique participants is reported in the Overall hepatic disorder AESIs category; a participant could have been represented in more than one of the individual hepatic disorder AESIs.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Overall hepatic disorder AESIs | 1.5 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | AST increased | 0.4 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | ALT increased | 0.3 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Hepatic enzyme increased | 0.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Blood bilirubin increased | 0.4 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Liver function test abnormal | 0.3 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Liver function test increased | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Hepatic enzyme abnormal | 0.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Transaminases increased | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | PHLC [AST &/or ALT>3 x ULN, concurrent TB>2 x ULN] | 0.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | AST and/or ALT >3 x ULN | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Total bilirubin >2 x ULN | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | AST and/or ALT >3 x ULN | 0.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Overall hepatic disorder AESIs | 2.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Liver function test increased | 0.2 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | AST increased | 1.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | PHLC [AST &/or ALT>3 x ULN, concurrent TB>2 x ULN] | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | ALT increased | 0.8 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Hepatic enzyme abnormal | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Hepatic enzyme increased | 0.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Total bilirubin >2 x ULN | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Blood bilirubin increased | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Transaminases increased | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hepatic Disorders | Liver function test abnormal | 0.1 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia
Treatment-emergent AESIs were predefined and monitored throughout the study. Hypoglycemia was assessed using the following preferred terms: hypoglycaemia (system organ class: metabolism and nutrition disorders); blood glucose abnormal and blood glucose decreased (system organ class: investigations). The percentage of unique participants is reported in the Overall hypoglycemia AESIs category; a participant could have been represented in more than one of the individual hypoglycemia AESIs.
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Overall hypoglycemia AESIs | 3.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Hypoglycaemia | 3.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Blood glucose abnormal | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Blood glucose decreased | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Blood glucose decreased | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Overall hypoglycemia AESIs | 2.2 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Blood glucose abnormal | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Hypoglycemia | Hypoglycaemia | 2.2 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis
Treatment-emergent AESIs were predefined and monitored throughout the study. Metabolic acidosis was assessed using the preferred term metabolic acidosis (system organ class: metabolism and nutrition disorders).
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Metabolic Acidosis | 0.1 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder
Treatment-emergent AESIs were predefined and monitored throughout the study. Muscular safety was assessed using the following preferred terms and laboratory abnormalities: myalgia, muscle spasms, pain in extremity, muscular weakness (system organ class: musculoskeletal and connective tissue disorders), and creatine kinase \>5 ULN (repeated and confirmed). The percentage of unique participants is reported in the Overall muscular disorder AESIs category; a participant could have been represented in more than one of the individual muscular disorder AESIs.
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Overall muscular disorder AESIs | 10.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Myalgia | 6.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Muscle spasms | 2.7 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Pain in extremity | 2.2 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Muscular weakness | 0.5 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Creatine kinase >5 ULN | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Muscular weakness | 0.6 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Overall muscular disorder AESIs | 13.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Pain in extremity | 3.4 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Myalgia | 6.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Creatine kinase >5 ULN | 0.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Muscular Disorder | Muscle spasms | 4.2 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder
Treatment-emergent AESIs were predefined and monitored throughout the study. Neurocognitive disorder was assessed using the following preferred terms: memory impairment, amnesia, and cognitive disorder (system organ class: nervous system disorders); confusional state and disorientation (system organ class: psychiatric disorders). The percentage of unique participants is reported in the Overall neurocognitive disorder AESIs category; a participant could have been represented in more than one of the individual neurocognitive disorder AESIs.
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Overall neurocognitive disorder AESIs | 0.9 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Memory impairment | 0.5 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Amnesia | 0.4 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Cognitive disorder | 0.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Confusional state | 0.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Disorientation | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Confusional state | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Overall neurocognitive disorder AESIs | 0.7 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Cognitive disorder | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Memory impairment | 0.3 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Disorientation | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Neurocognitive Disorder | Amnesia | 0.2 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus
Treatment-emergent AESIs were predefined and monitored throughout the study. New onset or worsening diabetes was assessed using the following preferred terms: type 2 diabetes mellitus, diabetes mellitus, hyperglycaemia, glucose tolerance impaired, diabetes mellitus inadequate control, and impaired fasting glucose (system organ class: metabolism and nutrition disorders); blood glucose increased, glycosylated haemoglobin increased, blood glucose abnormal, and glucose urine present (system organ class: investigations); and glycosuria (system organ class: renal and urinary disorders). The percentage of unique participants is reported in the Overall new onset/worsening diabetes mellitus AESIs category; a participant could have been represented in more than one of the individual new onset/worsening diabetes mellitus AESIs.
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Type 2 diabetes mellitus | 0.9 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Impaired fasting glucose | 0.3 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Hyperglycaemia | 0.7 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Blood glucose increased | 1.2 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Overall new onset/worsening diabetes mellitus AESI | 5.4 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glycosylated haemoglobin increased | 0.5 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glucose tolerance impaired | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Blood glucose abnormal | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Diabetes mellitus | 0.9 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glucose urine present | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Diabetes mellitus inadequate control | 0.4 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glycosuria | 0.3 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glycosuria | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Overall new onset/worsening diabetes mellitus AESI | 3.3 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Type 2 diabetes mellitus | 1.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Diabetes mellitus | 0.4 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Hyperglycaemia | 0.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glucose tolerance impaired | 0.4 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Diabetes mellitus inadequate control | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Impaired fasting glucose | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Blood glucose increased | 0.7 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glycosylated haemoglobin increased | 0.0 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Blood glucose abnormal | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: New Onset or Worsening Diabetes Mellitus | Glucose urine present | 0.0 percentage of participants |
Primary
Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder
Treatment-emergent AESIs were predefined and monitored throughout the study. TEAEs potentially related to renal events were assessed using the following preferred terms: renal failure, renal impairment, acute kidney injury (system organ class: renal and urinary disorders); blood creatinine increased, glomerular filtration rate decreased, blood urea increased, estimated glomerular filtration rate (eGFR) \<30 milliliter per minute per 1.73 square meter (ml/min/1.73m\^2), and change from baseline in creatinine \>1 mg/dL (system organ class: investigations); and gout (system organ class: metabolism and nutrition disorders). The percentage of unique participants is reported in the Overall renal disorder AESIs category; a participant could have been represented in more than one of the individual renal disorder AESIs.
Time frame: Up to approximately 52 weeks
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Renal impairment | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Blood urea increased | 0.1 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Blood creatinine increased | 0.4 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Gout | 0.3 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Acute kidney injury | 0.3 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Change from baseline in creatinine >1 mg/dL | 0.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Glomerular filtration rate decreased | 0.0 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | eGFR <30 mL/min/1.73 m^2 | 0.4 percentage of participants |
| Placebo | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Renal failure | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | eGFR <30 mL/min/1.73 m^2 | 0.9 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Renal failure | 0.9 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Renal impairment | 0.4 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Acute kidney injury | 0.3 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Blood creatinine increased | 0.8 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Glomerular filtration rate decreased | 0.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Blood urea increased | 0.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Gout | 1.2 percentage of participants |
| Bempedoic Acid | Percentage of Participants With the Indicated Event of Special Interest: Renal Disorder | Change from baseline in creatinine >1 mg/dL | 0.1 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs, defined as adverse events (AEs) that began or worsened in severity after the first dose of double-blind study drug and up to 30 days after receiving the last dose of double-blind study drug, were collected and reported.
Time frame: Up to approximately 52 weeks
Population: Safety Population: all randomized participants who received at least 1 dose of investigational medicinal product. Participants were included in the treatment group that they received, regardless of their randomized treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 78.7 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any serious TEAE | 14.0 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any fatal TEAE | 0.3 percentage of participants |
| Placebo | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study drug | 7.1 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE leading to discontinuation of study drug | 10.9 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any TEAE | 78.5 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any fatal TEAE | 0.9 percentage of participants |
| Bempedoic Acid | Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | Any serious TEAE | 14.5 percentage of participants |
Secondary
Absolute Change From Baseline to Week 12 in LDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Absolute change from baseline was calculated as: LDL-C value at Week 12 minus Baseline value. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline to Week 12 in LDL-C | 0.43 mg/dL | Standard Deviation 27.04 |
| Bempedoic Acid | Absolute Change From Baseline to Week 12 in LDL-C | -19.23 mg/dL | Standard Deviation 24.01 |
Secondary
Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(LDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Least Square mean= LS mean. Percent change was analyzed using the analysis of covariance (ANCOVA) method, which included treatment, randomization stratum as factors, and baseline value as covariate.
Time frame: Baseline; Week 12
Population: Full Analysis Set: all randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | 1.6 percent change | Standard Error 0.86 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Low-density Lipoprotein Cholesterol (LDL-C) | -16.5 percent change | Standard Error 0.52 |
p-value: <0.00195% CI: [-20, -16.1]ANCOVA
Other Pre-specified
Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52
The percentage of participants who achieved lowering in lipid values of LDL-C below 70 mg/dL have been reported. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Week 12, Week 24, and Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 | Week 12 | 9.0 Percentage of participants |
| Placebo | Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 | Week 24 | 10.2 Percentage of participants |
| Placebo | Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 | Week 52 | 9.5 Percentage of participants |
| Bempedoic Acid | Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 | Week 12 | 32.4 Percentage of participants |
| Bempedoic Acid | Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 | Week 24 | 32.0 Percentage of participants |
| Bempedoic Acid | Percentage of Participants Achieving LDL-C <70 mg/dL at Week 12, 24, and 52 | Week 52 | 28.2 Percentage of participants |
p-value: <0.001Chi-squared
Other Pre-specified
Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(apoB value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) | 3.3 percent change | Standard Error 0.7 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Apolipoprotein B (apoB) | -8.6 percent change | Standard Error 0.47 |
p-value: <0.00195% CI: [-13.6, -10.2]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(hsCRP value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
Time frame: Baseline; Week 12
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | 2.6 percent change | Standard Error 91.9 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP) | -22.4 percent change | Standard Error 72.5 |
p-value: <0.00195% CI: [-26.96, -16]Wilcoxon (Mann-Whitney)
Other Pre-specified
Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(non-HDL-C value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
Time frame: Baseline; Week 12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | 1.5 percent change | Standard Error 0.76 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) | -11.9 percent change | Standard Error 0.48 |
p-value: <0.00195% CI: [-15.1, -11.6]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(TC value at Week 12 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
Time frame: Baseline; Week 12
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | 0.8 percent change | Standard Error 0.57 |
| Bempedoic Acid | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | -10.3 percent change | Standard Error 0.37 |
p-value: <0.00195% CI: [-12.5, -9.8]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 24 in apoB
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(apoB value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in apoB | 4.8 percent change | Standard Deviation 20.41 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in apoB | -7.1 percent change | Standard Deviation 20.01 |
Other Pre-specified
Percent Change From Baseline to Week 24 in hsCRP
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(hsCRP value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in hsCRP | 2.727 percent change |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in hsCRP | -16.382 percent change |
Other Pre-specified
Percent Change From Baseline to Week 24 in LDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(LDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Missing data were imputed with the use of a pattern-mixture model to account for adherence to the trial regimen. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
Time frame: Baseline; Week 24
Population: Full Analysis Set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in LDL-C | 1.2 percent change | Standard Error 0.88 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in LDL-C | -14.9 percent change | Standard Error 0.6 |
p-value: <0.00195% CI: [-18.2, -14]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 24 in Non-HDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(non-HDL-C value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in Non-HDL-C | 1.61 percent change | Standard Deviation 20.91 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in Non-HDL-C | -11.69 percent change | Standard Deviation 19.8 |
Other Pre-specified
Percent Change From Baseline to Week 24 in TC
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(TC value at Week 24 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Baseline; Week 24
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 24 in TC | 1.15 percent change | Standard Deviation 15.349 |
| Bempedoic Acid | Percent Change From Baseline to Week 24 in TC | -9.86 percent change | Standard Deviation 15.358 |
Other Pre-specified
Percent Change From Baseline to Week 52 in apoB
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for apoB. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(apoB value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in apoB | 3.4 percent change | Standard Deviation 20.24 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in apoB | -6.0 percent change | Standard Deviation 22.54 |
Other Pre-specified
Percent Change From Baseline to Week 52 in hsCRP
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to first dose of study drug. Percent change from baseline was calculated as: \[(hsCRP value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in hsCRP | 1.818 percent change |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in hsCRP | -14.445 percent change |
Other Pre-specified
Percent Change From Baseline to Week 52 in LDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(LDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed. Percent change was analyzed using the ANCOVA method, which included treatment, randomization stratum as factors, and baseline value as covariate.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in LDL-C | 1.0 percent change | Standard Error 0.92 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in LDL-C | -12.6 percent change | Standard Error 0.66 |
p-value: <0.00195% CI: [-15.8, -11.3]ANCOVA
Other Pre-specified
Percent Change From Baseline to Week 52 in Non-HDL-C
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(non-HDL-C value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in Non-HDL-C | 0.65 percent change | Standard Deviation 21.438 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in Non-HDL-C | -10.07 percent change | Standard Deviation 22.097 |
Other Pre-specified
Percent Change From Baseline to Week 52 in TC
Blood samples were drawn after a minimum 10-hour fast (water was allowed) at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the mean of the values at screening (Week -2) and predose Day 1/Week 0. Percent change from baseline was calculated as: \[(TC value at Week 52 minus Baseline value) divided by (Baseline Value)\] multiplied by 100. Observed data was used for the analysis, no imputation for the missing data was performed.
Time frame: Baseline; Week 52
Population: Full Analysis Set. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 52 in TC | 0.38 percent change | Standard Deviation 16.18 |
| Bempedoic Acid | Percent Change From Baseline to Week 52 in TC | -8.92 percent change | Standard Deviation 16.945 |