Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Other |
To Evaluate Plasma Cmax of ISIS 681257 Across Different Doses and Dose Regimens. |
Cmax will be calculated for the treatment groups. |
6 months |
|
| Other |
To Evaluate Plasma Tmax of ISIS 681257 Across Different Doses and Dose Regimens. |
Tmax will be calculated for the treatment groups. |
6 months |
|
| Other |
To Evaluate Plasma AUC Values of ISIS 681257 Across Different Doses and Dose Regimens. |
AUC values will be calculated for the treatment groups. |
6 months |
|
| Primary |
Percent Change From Baseline in Fasting Lipoprotein A [Lp(a)] at the Primary Analysis Time Point |
An ANCOVA model was performed on the log ratio of Lp(a) value at the Primary Analysis Time Point to Lp(a) value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Lp(a) value at the Primary Analysis Time Point to Lp(a) value at Baseline - 1) × 100. |
Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E) |
|
| Primary |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
An adverse event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. TEAEs was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study. |
Up to 16 weeks post treatment period (up to approximately 1.3 years) |
|
| Primary |
Number of Participants With TEAEs by Maximum Severity |
An AE was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. TEAEs was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study. The severity of TEAEs was assessed based on the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death. |
Up to 16 weeks post treatment period (up to approximately 1.3 years) |
|
| Primary |
Number of Participants With TEAEs Leading to Study Discontinuation |
An AE was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. TEAE was defined as any AE with onset after the first administration of study medication through the end of the study, or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through the end of the study. |
Up to 16 weeks post treatment period (up to approximately 1.3 years) |
|
| Secondary |
Percent Change From Baseline in Fasting Low-Density Lipoprotein Cholesterol (LDL-C) |
An ANCOVA model was performed on the log ratio of LDL-C value at the Primary Analysis Time Point to LDL-C value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of LDL-C value at the Primary Analysis Time Point to LDL-C value at Baseline - 1) × 100. |
Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E) |
|
| Secondary |
Percentage of Participants Who Achieved Plasma Lp(a) = 125 Nanomoles Per Liter (Nmol/L) or = 50 Milligrams Per Deciliter (mg/dL) |
The percentage of participants who achieved = 125 nmol/L or = 50 mg/dL in fasting Lp(a) at the primary analysis time point were compared between each ISIS 681257 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline Lp(a) as a covariate. |
Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E) |
|
| Secondary |
Percentage of Participants Who Achieved Plasma Lp(a) = 75 Nmol/L or = 30 mg/dL |
The percentage of participants who achieved = 75 nmol/L or = 30 mg/dL in fasting Lp(a) at the primary analysis time point were compared between each ISIS 681257 treatment group and pooled placebo group using a logistic regression model with log-transformed baseline Lp(a) as a covariate. |
Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E) |
|
| Secondary |
Percent Change From Baseline in the Plasma Levels of Apolipoprotein B (apoB) |
An ANCOVA model was performed on the log ratio of apoB value at the Primary Analysis Time Point to apoB value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of apoB value at the Primary Analysis Time Point to apoB value at Baseline - 1) × 100. |
Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E) |
|
| Secondary |
Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein(a) [OxPL-apo(a)] |
An ANCOVA model was performed on the log ratio of OxPL-apo(a) value at the Primary Analysis Time Point to OxPL-apo(a) value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of OxPL-apo(a) value at the Primary Analysis Time Point to OxPL-apo(a) value at Baseline - 1) × 100. |
Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E) |
|
| Secondary |
Percent Change From Baseline in the Plasma Levels of Oxidized Phospholipids (OxPL) on Apolipoprotein B (OxPL-apoB) |
An ANCOVA model was performed on the log ratio of OxPL-apoB value at the Primary Analysis Time Point to OxPL-apoB value at Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of OxPL-apoB value at the Primary Analysis Time Point to OxPL-apoB value at Baseline - 1) × 100. |
Baseline and Month 6 (Week 25 for Cohorts A, B and C and Week 27 for Cohorts D and E) |
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