| Outcome Measures: |
Primary: Percent Change From Baseline to Week 12/End of Study (EOS) in Low-density Lipoprotein Cholesterol (LDL-C), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the average of LDL-C values at the Screening Visit 3 (Visit S3) and the Treatment Visit 1 (Visit T1) (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for LDL-C was analyzed using analysis of covariance (ANCOVA), with treatment as factor and Baseline lipid parameter as a covariate. Missing data for LDL-C was imputed using the last observation carried forward (LOCF) method. Percent change from Baseline was calculated as: (\[LDL-C value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used., Baseline; Week 12 | Secondary: Percent Change From Baseline to Week 12/EOS in LDL-C (Comparing Ezetimibe With Placebo), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the average of LDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for LDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for LDL-C was imputed using the LOCF method. Percent change from Baseline was calculated as: (\[LDL-C value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in High-sensitivity C-reactive Protein (hsCRP), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for hsCRP. Baseline was defined as the last value prior to the first dose of investigational medicinal product (IMP). Percent change from Baseline for hsCRP was analyzed using a non-parametric approach. Percent change from Baseline was calculated as: (\[hsCRP value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For hsCRP, if a measured hsCRP value was available, measured hsCRP was used., Baseline; Week 12|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 at pre-specified intervals. Samples were collected and analyzed for non-HDL-C. Baseline was defined as the average of non-HDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for non-HDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for non-HDL-C was imputed using the LOCF method. Percent change from Baseline was calculated as: (\[non-HDL-C value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For non-HDL-C, if a measured non-HDL-C value was available, measured non-HDL-C was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in Total Cholesterol (TC), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for TC. Baseline was defined as the average of TC values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for TC was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for TC was imputed using the LOCF method. Percent change from Baseline was calculated as: (\[TC value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For TC, if a measured TC value was available, measured TC was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in Apolipoprotein B (Apo B), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for apo B. Baseline was defined as the last value prior to the first dose of IMP. Percent change from Baseline for TC was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for apo B was imputed using the LOCF method. Percent change from Baseline was calculated as: (\[apo B value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For apo B, if a measured apo B value was available, measured apo B was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in Triglycerides (TGs), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for TGs. Baseline was defined as the average of TG values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for TGs was analyzed using a non-parametric approach. Percent change from Baseline was calculated as: (\[TG value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For TGs, if a measured TG value was available, measured TG was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in High-density Lipoprotein Cholesterol (HDL-C), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for HDL-C. Baseline was defined as the average of HDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. Percent change from Baseline for HDL-C was analyzed using ANCOVA, with treatment as factor and Baseline lipid parameter as a covariate. Missing data for HDL-C was imputed using the LOCF method. Percent change from Baseline was calculated as: (\[HDL-C value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For HDL-C, if a measured HDL-C value was available, measured HDL-C was used., Baseline; Week 12|Number of Participants With LDL-C <70 Milligrams Per Deciliter (mg/dL) at Week 12, Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used., Week 12|Secondary Outcome Measure: Number of Participants With an LDL-C Reduction of ≥50% From Baseline at Week 12, Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for LDL-C. Baseline was defined as the average of LDL-C values at Visit S3 and Visit T1 (last 2 non-missing values on or prior to Day 1). If only 1 value was available, the single value was used as Baseline. LDL-C reduction from Baseline was calculated as the LDL-C value at Week 12 minus the Baseline value. For LDL-C, if a measured LDL-C value was available, measured LDL-C was used., Baseline; Week 12|Change From Baseline to Week 12 in Hemoglobin A1C (HbA1c), Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for HbA1c. Baseline was defined as the last value prior to the first dose of IMP (on or before Visit T1). Change from Baseline was calculated as the HbA1c value at Week 12 minus the Baseline value. For HbA1c, if a measured HbA1c value was available, measured HbA1c was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in HbA1c, Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for HbA1c. Baseline was defined as the last value prior to the first dose of IMP (on or before Visit T1). Percent change from Baseline for HbA1C was analyzed using ANCOVA, with treatment as factor and Baseline HbA1C value as a covariate. Percent change from Baseline for HbA1c was calculated as: (\[HbA1c value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For HbA1c, if a measured HbA1c value was available, measured HbA1c was used., Baseline; Week 12 | Other: Percent Change From Baseline to Week 12 in Fasting Plasma Glucose, Blood samples were drawn after a minimum 10-hour fast at pre-specified intervals. Samples were collected and analyzed for fasting plasma glucose. Baseline was defined as the last value prior to the first dose of study drug (on or before T1). Percent change from Baseline for fasting plasma glucose was analyzed using ANCOVA, with treatment as factor and Baseline fasting plasma glucose as a covariate. Percent change from Baseline for fasting plasma glucose was calculated as: (\[fasting plasma glucose value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For fasting plasma glucose, if a measured fasting plasma glucose value was available, measured fasting plasma glucose was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in 2-hour Post Prandial Plasma Glucose (PPG), Blood samples were drawn 2 hours ± 5 minutes after the start of the meal. Samples were collected and analyzed for PPG. Baseline was defined as the last value prior to the first dose of study drug (on or before T1). Percent change from Baseline for PPG was calculated as: (\[PPG value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100. For PPG, if a measured PPG value was available, measured PPG was used., Baseline; Week 12|Percent Change From Baseline to Week 12 in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Index, The HOMA-IR index was calculated from the fasting glucose and insulin values that were obtained at each clinic visit (Day 1/Visit T1, Week 4/Visit T2, and Week 12/Visit T3) during the double-blind treatment period, using the formula: (fasting glucose \[millimoles per milliliter {mmol/ml}\] x fasting insulin \[micro International Units per milliliter {μIU/ml}\]) divided by 22.5. Percent change from Baseline for HOMA-IR index was analyzed using ANCOVA, with treatment as factor and Baseline HOMA-IR index as a covariate. Baseline was defined as the last value prior to the first dose of study drug (on or before T1). Percent change from Baseline for HOMA-IR index was calculated as: (\[HOMA-IR index value at Week 12 minus Baseline value\] divided by \[Baseline value\]) multiplied by 100., Baseline; Week 12|Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) that began or worsened in severity on or after the first dose of double-blind IMP through 30 days after the last dose of double-blind IMP. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, including control, and which does not necessarily have a causal relationship with treatment. An AE is: any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; any new disease or exacerbation of an existing disease; any deterioration in non-protocol-required measurements of a laboratory value or other clinical test (e.g., electrocardiogram or x-ray) that results in symptoms, a change in treatment, or discontinuation from IMP; or an adverse drug reaction., up to approximately 16 weeks
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| Locations: |
Clinical Trials Research, Lincoln, California, 95648, United States|FInlay Medical Research, Miami, Florida, 33126, United States|L-MARC Research Center, Louisville, Kentucky, 40213, United States|Hampton Roads Center for Clinical Research, Suffolk, Virginia, 23435, United States
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