Hypercholesterolemia, Hypertension
Conditions
Keywords
LDL, Cholesterol
Brief summary
This Phase 2 study will assess the efficacy and safety of ETC-1002 monotherapy versus placebo in participants with hypercholesterolemia and hypertension.
Interventions
DRUGETC-1002
ETC-1002 capsules taken once daily
DRUGPlacebo
Placebo capsules taken once daily
Sponsors
Medpace, Inc.
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
* Mean 24-hour ambulatory SBP greater than or equal to 130 mmHg * or- Mean 24-hour ambulatory DBP greater than or equal to 80 mmHg * Fasting LDL-C between 100 and 220 mg/dL * Fasting triglycerides less than 400 mg/dL * Body mass index (BMI) between 18 and 45 kg/m2
Exclusion criteria
* Known or suspected secondary hypertension or history of malignant hypertension * Taking more than two anti-hypertension medications at the first visit * History or current clinically significant cardiovascular disease * History or current type 1 diabetes or type 2 diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6 | Baseline; 6 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 -1 and Week 0. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. For the Week 6 endpoint, missing values at Week 6 were imputed using the last observation carried forward (LOCF) procedure, with only post-Baseline values carried forward. Modified Intent-to-Treat (mITT) Population is defined as all randomized participants who received at least 1 dose of study drug, had a Baseline assessment, and had at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) to Week 6 | Baseline; 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Mean Daytime SBP to Week 6 | Baseline; 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (\>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Mean Daytime DBP to Week 6 | Baseline; 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (\>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Mean Nighttime SBP to Week 6 | Baseline; 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (\>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Mean Nighttime DBP to Week 6 | Baseline; 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (\>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Sitting Cuff SBP to Week 6 | Baseline: 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Sitting Cuff DBP to Week 6 | Baseline; 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value. |
| Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) to Week 6 | Baseline; 6 weeks | A non-parametric analysis was performed for hsCRP parameters. 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 last value prior to the first dose of study medication. If hsCRP was \<0.2, 0.1 was imputed for analysis. The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6 | Baseline; 6 weeks | Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. |
| Percent Change From Baseline in Apolipoprotein B (ApoB) to Week 6 | Baseline; 6 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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. |
| Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) to Week 6 | Baseline; 6 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 last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. |
| Percent Change From Baseline in Triglycerides (TG) to Week 6 | Baseline; 6 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 -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value. Data was analyzed using non-parametric analysis. |
| Percent Change From Baseline in HDL-C to Week 6 | Baseline; 6 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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. |
| Percent Change From Baseline in Free Fatty Acids (FFA) to Week 6 | Baseline; 6 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 -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value. |
| Change From Baseline in Body Weight to Week 6 | Baseline; 6 weeks | Baseline was defined as the mean of the values from Week -1 and Week 0. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. |
| Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Week 2, Week 4 and Week 6 | Plasma trough concentration is defined as the lowest concentration reached before the next dose is administered. |
| Percent Change From Baseline in Total Cholesterol to Week 6 | Baseline; 6 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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and value as a covariate. The Week 6 endpoint was the last available post-Baseline value. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching oral placebo capsules taken once daily for 6 weeks. | 72 |
| ETC-1002 180 mg Participants received oral bempedoic acid 180 milligrams (mg) daily for 6 weeks. | 71 |
| Total | 143 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Sponsor Request | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 6 |
Baseline characteristics
| Characteristic | ETC-1002 180 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 8.41 | 55.6 years STANDARD_DEVIATION 8.38 | 56.5 years STANDARD_DEVIATION 8.29 |
| Race/Ethnicity, Customized Asian | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants | 40 Participants | 23 Participants |
| Race/Ethnicity, Customized More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 49 Participants | 94 Participants | 45 Participants |
| Sex: Female, Male Female | 26 Participants | 61 Participants | 35 Participants |
| Sex: Female, Male Male | 45 Participants | 82 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 72 | 0 / 71 |
| other Total, other adverse events | 4 / 72 | 3 / 71 |
| serious Total, serious adverse events | 2 / 72 | 4 / 71 |
Outcome results
Primary
Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6
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 -1 and Week 0. Percent change from Baseline in LDL-C was analyzed using an analysis of covariance (ANCOVA) model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value. For the Week 6 endpoint, missing values at Week 6 were imputed using the last observation carried forward (LOCF) procedure, with only post-Baseline values carried forward. Modified Intent-to-Treat (mITT) Population is defined as all randomized participants who received at least 1 dose of study drug, had a Baseline assessment, and had at least 1 post-Baseline assessment, excluding any assessment taken more than 2 days after a dose of study drug
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6 | 3.16 Percent Change | Standard Error 2.133 |
| ETC-1002 180 mg | Percent Change From Baseline in Calculated Low-density Lipoprotein Cholesterol (LDL-C) to Week 6 | -21.08 Percent Change | Standard Error 2.196 |
p-value: <0.000195% CI: [-30.33, -18.15]ANCOVA
Secondary
Change From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) to Week 6 | -0.05 mmHg | Standard Deviation 0.76 |
| ETC-1002 180 mg | Change From Baseline in 24-hour Mean Diastolic Blood Pressure (DBP) to Week 6 | -1.10 mmHg | Standard Deviation 0.79 |
p-value: 0.346195% CI: [-3.25, 1.15]ANCOVA
Secondary
Change From Baseline in Body Weight to Week 6
Baseline was defined as the mean of the values from Week -1 and Week 0. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time frame: Baseline; 6 weeks
Population: Safety Population: all randomized participants who received at least 1 dose of study drug. Only participants with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Weight to Week 6 | -0.335 kilograms | Standard Deviation 1.59 |
| ETC-1002 180 mg | Change From Baseline in Body Weight to Week 6 | -0.009 kilograms | Standard Deviation 1.927 |
Secondary
Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6 | -0.64 millimeters of mercury (mmHg) | Standard Error 1.045 |
| ETC-1002 180 mg | Change From Baseline in Mean 24-hour Systolic Blood Pressure (SBP) to Week 6 | -2.28 millimeters of mercury (mmHg) | Standard Error 1.085 |
p-value: 0.280895% CI: [-4.62, 1.35]ANCOVA
Secondary
Change From Baseline in Mean Daytime DBP to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (\>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Daytime DBP to Week 6 | -0.01 mmHg | Standard Error 0.856 |
| ETC-1002 180 mg | Change From Baseline in Mean Daytime DBP to Week 6 | -1.47 mmHg | Standard Error 0.89 |
p-value: 0.248195% CI: [-3.93, 1.03]ANCOVA
Secondary
Change From Baseline in Mean Daytime SBP to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Daytime measurements were defined as those taken from 7 AM to 10 PM (\>7 AM and ≤10 PM). The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Daytime SBP to Week 6 | -0.35 mmHg | Standard Error 1.198 |
| ETC-1002 180 mg | Change From Baseline in Mean Daytime SBP to Week 6 | -2.66 mmHg | Standard Error 1.245 |
p-value: 0.185295% CI: [-5.74, 1.12]ANCOVA
Secondary
Change From Baseline in Mean Nighttime DBP to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (\>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Nighttime DBP to Week 6 | -0.52 mmHg | Standard Error 0.879 |
| ETC-1002 180 mg | Change From Baseline in Mean Nighttime DBP to Week 6 | -0.33 mmHg | Standard Error 0.913 |
p-value: 0.881795% CI: [-2.33, 2.71]ANCOVA
Secondary
Change From Baseline in Mean Nighttime SBP to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Nighttime measurements were defined as those taken from 10 PM to 7 AM (\>10 PM and ≤7 AM). The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Nighttime SBP to Week 6 | -1.18 mmHg | Standard Error 1.167 |
| ETC-1002 180 mg | Change From Baseline in Mean Nighttime SBP to Week 6 | -1.57 mmHg | Standard Error 1.212 |
p-value: 0.818195% CI: [-3.72, 2.94]ANCOVA
Secondary
Change From Baseline in Sitting Cuff DBP to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sitting Cuff DBP to Week 6 | -3.32 mmHg | Standard Error 0.82 |
| ETC-1002 180 mg | Change From Baseline in Sitting Cuff DBP to Week 6 | -2.53 mmHg | Standard Error 0.844 |
p-value: 0.506195% CI: [-1.54, 3.11]ANCOVA
Secondary
Change From Baseline in Sitting Cuff SBP to Week 6
Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Baseline was defined as the mean of the values from Weeks -1 and 0. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. Three BP measurements were collected at least 3 minutes apart, and the mean of the second and third measurements was calculated and used for summary and analysis. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline: 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sitting Cuff SBP to Week 6 | -4.98 mmHg | Standard Error 1.274 |
| ETC-1002 180 mg | Change From Baseline in Sitting Cuff SBP to Week 6 | -3.45 mmHg | Standard Error 1.311 |
p-value: 0.40495% CI: [-2.09, 5.15]ANCOVA
Secondary
Percent Change From Baseline in Apolipoprotein B (ApoB) to Week 6
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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Apolipoprotein B (ApoB) to Week 6 | 4.77 Percent Change | Standard Error 1.797 |
| ETC-1002 180 mg | Percent Change From Baseline in Apolipoprotein B (ApoB) to Week 6 | -14.13 Percent Change | Standard Error 1.911 |
p-value: <0.000195% CI: [-24.09, -13.71]ANCOVA
Secondary
Percent Change From Baseline in Free Fatty Acids (FFA) to Week 6
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 -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Free Fatty Acids (FFA) to Week 6 | 1.08 Percent Change |
| ETC-1002 180 mg | Percent Change From Baseline in Free Fatty Acids (FFA) to Week 6 | 9.56 Percent Change |
p-value: 0.309395% CI: [-8.21, 24.02]Wilcoxon Rank-Sum Test
Secondary
Percent Change From Baseline in HDL-C to Week 6
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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in HDL-C to Week 6 | 2.42 Percent Change | Standard Error 1.614 |
| ETC-1002 180 mg | Percent Change From Baseline in HDL-C to Week 6 | -5.76 Percent Change | Standard Error 1.661 |
p-value: 0.000695% CI: [-12.76, -3.59]ANCOVA
Secondary
Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) to Week 6
A non-parametric analysis was performed for hsCRP parameters. 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 last value prior to the first dose of study medication. If hsCRP was \<0.2, 0.1 was imputed for analysis. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: miTT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) to Week 6 | 19.61 Percent Change |
| ETC-1002 180 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) to Week 6 | -25.00 Percent Change |
p-value: <0.000195% CI: [-62.8, -25.21]Wilcoxon Rank-Sum Test
Secondary
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) to Week 6
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 last value prior to the first dose of study medication. Change from Baseline was calculated using an ANCOVA model with a term for treatment and Baseline value as a covariate. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) to Week 6 | 3.20 Percent Change | Standard Error 1.728 |
| ETC-1002 180 mg | Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) to Week 6 | -15.49 Percent Change | Standard Error 1.779 |
p-value: <0.000195% CI: [-23.62, -13.77]ANCOVA
Secondary
Percent Change From Baseline in Total Cholesterol to Week 6
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 -1 and Week 0. Change from Baseline was calculated using an ANCOVA model with terms for treatment and statin intolerance, and value as a covariate. The Week 6 endpoint was the last available post-Baseline value.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Total Cholesterol to Week 6 | 2.90 Percent Change | Standard Error 1.389 |
| ETC-1002 180 mg | Percent Change From Baseline in Total Cholesterol to Week 6 | -13.77 Percent Change | Standard Error 1.43 |
p-value: <0.000195% CI: [-20.63, -12.7]ANCOVA
Secondary
Percent Change From Baseline in Triglycerides (TG) to Week 6
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 -1 and Week 0. The Week 6 endpoint was the last available post-Baseline value. Data was analyzed using non-parametric analysis.
Time frame: Baseline; 6 weeks
Population: mITT Population. Only participants with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Triglycerides (TG) to Week 6 | -3.75 Percent Change |
| ETC-1002 180 mg | Percent Change From Baseline in Triglycerides (TG) to Week 6 | -0.07 Percent Change |
p-value: 0.368995% CI: [-6.78, 16.42]Wilcoxon Rank-Sum Test
Secondary
Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228
Plasma trough concentration is defined as the lowest concentration reached before the next dose is administered.
Time frame: Week 2, Week 4 and Week 6
Population: Pharmacokinetic Concentration Population: all randomized participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration value for study drug collected between 18 and 36 hours post-dose. Only participants with available data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Week 2, ETC-1002 | 6666.20 nanograms per milliliter (ng/mL) | Standard Deviation 4777.661 |
| Placebo | Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Week 4, ETC-1002 | 6817.45 nanograms per milliliter (ng/mL) | Standard Deviation 4543.944 |
| Placebo | Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Week 6, ETC-1002 | 6836.36 nanograms per milliliter (ng/mL) | Standard Deviation 3702.241 |
| Placebo | Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Week 2, ESP15228 | 1219.60 nanograms per milliliter (ng/mL) | Standard Deviation 783 |
| Placebo | Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Week 4, ESP15228 | 1220.79 nanograms per milliliter (ng/mL) | Standard Deviation 674.437 |
| Placebo | Plasma Trough Concentrations of ETC-1002 and Metabolite ESP15228 | Week 6, ESP15228 | 1221.32 nanograms per milliliter (ng/mL) | Standard Deviation 557.93 |