Dyslipidemia
Conditions
Brief summary
This Phase 2 proof-of-concept study will assess the lipid regulating efficacy and safety of ETC-1002 in subjects with hypercholesterolemia and either normal or elevated triglycerides.
Interventions
DRUGETC-1002
ETC-1002 daily for 12 weeks
DRUGPlacebo
Placebo daily for 12 weeks
Sponsors
Esperion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Major Inclusion Criteria: * Provision of written informed consent prior to any study-specific procedure * Fasting LDL-C between 130 and 220 mg/dL following wash-out of all lipid regulating medications and supplements * Fasting triglyceride \<400 mg/dL following wash-out of all lipid regulating medications and supplements * BMI between 18 and 35 mg/kg2 Major
Exclusion criteria
* Clinically significant cardiovascular disease, diabetes or uncontrolled hypertension * Females of child bearing potential (i.e., females who are not surgically sterile or post-menopausal)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. Least square (LS) mean percent change from Baseline to Week 12 was based on an analysis of covariance (ANCOVA) model with effects of treatment and triglyceride (TG) stratum and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the last observation carried forward (LOCF) procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and center and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TC values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoB values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoAI values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in Lipoprotein (a) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing Lipoprotein (a) values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing FFA values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP) | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the value from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing hsCRP values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in Non-HDL-C | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing non-HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in Total HDL Particles | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | up to 12 weeks | TEAEs were defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication. |
| Number of Participants With Clinically Significant Physical Examination Findings | up to 12 weeks | Clinical significance was determined by the investigator. |
| Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values | Baseline; up to 12 weeks | Clinical importance was determined by the investigator. |
| Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values | Baseline; up to 12 weeks | Clinical importance was determined by the investigator. |
| Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Week 12 | Laboratory abnormalities are laboratory values that are outside the normal range. |
| Percent Change From Baseline to Week 12 in Total LDL Particles | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
| Percent Change From Baseline to Week 12 in TG | Baseline; 12 weeks | Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TG values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward). |
Countries
United States
Participant flow
Recruitment details
A total of 177 participants were enrolled and treated across 11 study sites in the United States.
Pre-assignment details
During Screening, appropriate participants washed off all lipid-regulating drugs and supplements as necessary for 6 weeks prior to randomization. Participants not taking lipid-regulating medications or supplements for 4 weeks prior to Screening may have combined the S1 and Q1 visits. Participants with hypercholesterolemia were stratified into the normal (\<150 milligrams per deciliter \[mg/dL\]) or elevated (≥150 mg/dL) triglycerides (TG) stratum.
Participants by arm
| Arm | Count |
|---|---|
| ETC-1002 40 mg Participants received ETC-1002 40 milligrams (mg), orally, once daily for 12 weeks. | 45 |
| ETC-1002 80 mg Participants received ETC-1002 80 mg, orally, once daily for 12 weeks. | 44 |
| ETC-1002 120 mg Participants received ETC-1002 120 mg, orally, once daily for 12 weeks. | 44 |
| Placebo Participants received placebo, orally, once daily for 12 weeks. | 44 |
| Total | 177 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 3 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 | 1 |
| Overall Study | Participant Went Out of Town | 0 | 0 | 1 | 0 |
| Overall Study | Per Investigator/Sponsor/Regulatory Body | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo | ETC-1002 120 mg | ETC-1002 40 mg | ETC-1002 80 mg |
|---|---|---|---|---|---|
| Age, Continuous | 57.3 Years STANDARD_DEVIATION 9.52 | 55.5 Years STANDARD_DEVIATION 10.4 | 56.7 Years STANDARD_DEVIATION 9.92 | 58.4 Years STANDARD_DEVIATION 8.66 | 58.8 Years STANDARD_DEVIATION 9 |
| Calculated Low-density Lipoprotein Cholesterol (LDL-C) | 166.4 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 24.05 | 167.4 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 22.03 | 165.0 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 23.08 | 163.1 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 24.88 | 170.2 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 26.23 |
| LDL-C by Triglyceride (TG) Stratum Elevated Stratum, TG≥150 mg/dL | 171.7 mg/dL STANDARD_DEVIATION 25.73 | 168.2 mg/dL STANDARD_DEVIATION 25.94 | 169.8 mg/dL STANDARD_DEVIATION 27.25 | 172.9 mg/dL STANDARD_DEVIATION 24.35 | 175.7 mg/dL STANDARD_DEVIATION 26.46 |
| LDL-C by Triglyceride (TG) Stratum Normal Stratum, TG<150 mg/dL | 161.2 mg/dL STANDARD_DEVIATION 21.15 | 166.6 mg/dL STANDARD_DEVIATION 17.87 | 160.2 mg/dL STANDARD_DEVIATION 17.3 | 153.8 mg/dL STANDARD_DEVIATION 22.06 | 164.6 mg/dL STANDARD_DEVIATION 25.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 6 Participants | 2 Participants | 7 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 152 Participants | 37 Participants | 41 Participants | 38 Participants | 36 Participants |
| Sex: Female, Male Female | 79 Participants | 13 Participants | 19 Participants | 26 Participants | 21 Participants |
| Sex: Female, Male Male | 98 Participants | 31 Participants | 25 Participants | 19 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 44 | 0 / 44 | 0 / 44 |
| other Total, other adverse events | 15 / 45 | 18 / 44 | 17 / 44 | 17 / 44 |
| serious Total, serious adverse events | 0 / 45 | 0 / 44 | 0 / 44 | 1 / 44 |
Outcome results
Primary
Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. Least square (LS) mean percent change from Baseline to Week 12 was based on an analysis of covariance (ANCOVA) model with effects of treatment and triglyceride (TG) stratum and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the last observation carried forward (LOCF) procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: Modified Intent-to-Treat (mITT) Population: all randomized participants who received at least 1 dose of study medication and had a Baseline assessment and at least 1 post-Baseline assessment, excluding any assessments taken more than 2 days after a dose of study medication
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) | -17.9 Percent Change | Standard Error 2.17 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) | -25.0 Percent Change | Standard Error 2.12 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) | -26.6 Percent Change | Standard Error 2.16 |
| Placebo | Percent Change From Baseline to Week 12 in Calculated Low-Density Lipoprotein-Cholesterol (LDL-C) | -2.1 Percent Change | Standard Error 2.16 |
p-value: <0.000195% CI: [-21.8, -9.7]ANCOVA
p-value: <0.000195% CI: [-28.9, -16.9]ANCOVA
p-value: <0.000195% CI: [-30.5, -18.4]ANCOVA
Primary
Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and center and Baseline value as a covariate. Missing LDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Normal (TG<150 mg/dL) | -17.8 Percent Change | Standard Error 2.92 |
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Elevated (TG≥150 mg/dL) | -17.8 Percent Change | Standard Error 3.21 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Elevated (TG≥150 mg/dL) | -28.1 Percent Change | Standard Error 3.22 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Normal (TG<150 mg/dL) | -21.9 Percent Change | Standard Error 2.73 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Normal (TG<150 mg/dL) | -29.2 Percent Change | Standard Error 2.72 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Elevated (TG≥150 mg/dL) | -23.6 Percent Change | Standard Error 3.37 |
| Placebo | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Elevated (TG≥150 mg/dL) | -4.5 Percent Change | Standard Error 3.22 |
| Placebo | Percent Change From Baseline to Week 12 in LDL-C by Triglyceride (TG) Stratum | Normal (TG<150 mg/dL) | 0.3 Percent Change | Standard Error 2.89 |
Secondary
Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values
Clinical importance was determined by the investigator.
Time frame: Baseline; up to 12 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETC-1002 40 mg | Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values | 0 Participants |
| ETC-1002 80 mg | Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values | 0 Participants |
| ETC-1002 120 mg | Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values | 0 Participants |
| Placebo | Number of Participants With Clinically Important Changes From Baseline in Electrocardiogram Values | 0 Participants |
Secondary
Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values
Clinical importance was determined by the investigator.
Time frame: Baseline; up to 12 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETC-1002 40 mg | Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values | 0 Participants |
| ETC-1002 80 mg | Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values | 0 Participants |
| ETC-1002 120 mg | Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values | 0 Participants |
| Placebo | Number of Participants With Clinically Important Changes From Baseline in Vital Sign Values | 0 Participants |
Secondary
Number of Participants With Clinically Significant Physical Examination Findings
Clinical significance was determined by the investigator.
Time frame: up to 12 weeks
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETC-1002 40 mg | Number of Participants With Clinically Significant Physical Examination Findings | 2 Participants |
| ETC-1002 80 mg | Number of Participants With Clinically Significant Physical Examination Findings | 2 Participants |
| ETC-1002 120 mg | Number of Participants With Clinically Significant Physical Examination Findings | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Physical Examination Findings | 2 Participants |
Secondary
Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12
Laboratory abnormalities are laboratory values that are outside the normal range.
Time frame: Week 12
Population: Safety Population. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Alanine aminotransferase | 4 Participants |
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Total bilirubin | 1 Participants |
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Hemoglobin | 5 Participants |
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Leukocytes | 3 Participants |
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Aspartate aminotransferase | 5 Participants |
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatine kinase | 12 Participants |
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatinine | 1 Participants |
| ETC-1002 40 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Uric acid | 6 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Hemoglobin | 8 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Leukocytes | 2 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Aspartate aminotransferase | 6 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Uric acid | 8 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatine kinase | 8 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Alanine aminotransferase | 3 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatinine | 0 Participants |
| ETC-1002 80 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Total bilirubin | 1 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Uric acid | 6 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Hemoglobin | 4 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatinine | 1 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatine kinase | 3 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Total bilirubin | 0 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Leukocytes | 1 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Alanine aminotransferase | 3 Participants |
| ETC-1002 120 mg | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Aspartate aminotransferase | 8 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Alanine aminotransferase | 4 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Aspartate aminotransferase | 2 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatinine | 0 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Uric acid | 3 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Creatine kinase | 5 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Hemoglobin | 2 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Total bilirubin | 1 Participants |
| Placebo | Number of Participants With the Indicated Abnormal Laboratory Parameter Values at Week 12 | Leukocytes | 1 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as adverse events (AEs) that began or worsened in severity after the first dose of study medication, occurring up to 30 days after the last dose of study medication.
Time frame: up to 12 weeks
Population: Safety Population: all randomized participants who received at least 1 dose of study medication
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETC-1002 40 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 34 Participants |
| ETC-1002 80 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 32 Participants |
| ETC-1002 120 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 31 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 33 Participants |
Secondary
Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoAI values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI) | 2.9 Percent Change | Standard Error 1.96 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI) | -2.7 Percent Change | Standard Error 1.95 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI) | 0.0 Percent Change | Standard Error 1.97 |
| Placebo | Percent Change From Baseline to Week 12 in Apolipoprotein AI (ApoAI) | -3.1 Percent Change | Standard Error 1.95 |
Secondary
Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the value from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing ApoB values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) | -14.6 Percent Change | Standard Error 1.83 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) | -18.4 Percent Change | Standard Error 1.82 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) | -22.1 Percent Change | Standard Error 1.84 |
| Placebo | Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) | -0.9 Percent Change | Standard Error 1.83 |
Secondary
Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing FFA values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA) | 2.5 Percent Change | Standard Error 6.15 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA) | -14.4 Percent Change | Standard Error 6.08 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA) | 5.3 Percent Change | Standard Error 6.34 |
| Placebo | Percent Change From Baseline to Week 12 in Free Fatty Acids (FFA) | 3.6 Percent Change | Standard Error 6.09 |
Secondary
Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C) | 7.2 Percent Change | Standard Error 2.22 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C) | 0.9 Percent Change | Standard Error 2.12 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C) | 4.4 Percent Change | Standard Error 2.16 |
| Placebo | Percent Change From Baseline to Week 12 in High-Density Lipoprotein-Cholesterol (HDL-C) | 2.4 Percent Change | Standard Error 2.18 |
Secondary
Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the value from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing hsCRP values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP) | 18.4 Percent Change | Standard Error 42.45 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP) | 57.0 Percent Change | Standard Error 42.44 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP) | 48.0 Percent Change | Standard Error 43.24 |
| Placebo | Percent Change From Baseline to Week 12 in High-Sensitivity C-Reactive Protein (hsCRP) | 86.6 Percent Change | Standard Error 42.45 |
Secondary
Percent Change From Baseline to Week 12 in Lipoprotein (a)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing Lipoprotein (a) values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Lipoprotein (a) | 0.3 Percent Change | Standard Error 5.2 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Lipoprotein (a) | 7.6 Percent Change | Standard Error 5.2 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Lipoprotein (a) | 16.2 Percent Change | Standard Error 5.27 |
| Placebo | Percent Change From Baseline to Week 12 in Lipoprotein (a) | -2.7 Percent Change | Standard Error 5.22 |
Secondary
Percent Change From Baseline to Week 12 in Non-HDL-C
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing non-HDL-C values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Non-HDL-C | -17.4 Percent Change | Standard Error 2.01 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Non-HDL-C | -22.7 Percent Change | Standard Error 1.95 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Non-HDL-C | -23.0 Percent Change | Standard Error 2 |
| Placebo | Percent Change From Baseline to Week 12 in Non-HDL-C | -2.3 Percent Change | Standard Error 2 |
Secondary
Percent Change From Baseline to Week 12 in TG
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TG values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in TG | -15.1 Percent Change | Standard Error 4.29 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in TG | -10.6 Percent Change | Standard Error 4.16 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in TG | 1.1 Percent Change | Standard Error 4.26 |
| Placebo | Percent Change From Baseline to Week 12 in TG | -1.2 Percent Change | Standard Error 4.29 |
Secondary
Percent Change From Baseline to Week 12 in Total Cholesterol (TC)
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Weeks -1 and 0. LS mean percent change from Baseline to Week 12 based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing TC values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | -11.5 Percent Change | Standard Error 1.53 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | -17.8 Percent Change | Standard Error 1.5 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | -17.1 Percent Change | Standard Error 1.53 |
| Placebo | Percent Change From Baseline to Week 12 in Total Cholesterol (TC) | -1.4 Percent Change | Standard Error 1.53 |
Secondary
Percent Change From Baseline to Week 12 in Total HDL Particles
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Total HDL Particles | 5.7 Percent Change | Standard Error 1.78 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Total HDL Particles | 3.6 Percent Change | Standard Error 1.74 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Total HDL Particles | 7.3 Percent Change | Standard Error 1.84 |
| Placebo | Percent Change From Baseline to Week 12 in Total HDL Particles | 0.4 Percent Change | Standard Error 1.75 |
Secondary
Percent Change From Baseline to Week 12 in Total LDL Particles
Percent change from Baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week 0. LS mean percent change from Baseline to Week 12 was based on an ANCOVA model with effects of treatment and TG stratum and Baseline value as a covariate. Missing values at Week 12 were imputed using the LOCF procedure (only post-Baseline values were carried forward).
Time frame: Baseline; 12 weeks
Population: mITT Population. Only participants with available date were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ETC-1002 40 mg | Percent Change From Baseline to Week 12 in Total LDL Particles | -14.8 Percent Change | Standard Error 2.26 |
| ETC-1002 80 mg | Percent Change From Baseline to Week 12 in Total LDL Particles | -16.3 Percent Change | Standard Error 2.23 |
| ETC-1002 120 mg | Percent Change From Baseline to Week 12 in Total LDL Particles | -20.7 Percent Change | Standard Error 2.34 |
| Placebo | Percent Change From Baseline to Week 12 in Total LDL Particles | 1.9 Percent Change | Standard Error 2.22 |