Study of ISIS 703802 in Participants With Hypertriglyceridemia, Type 2 Diabetes Mellitus, and Nonalcoholic Fatty Liver Disease

Change From Baseline in Angiopoietin-Like 3 Protein at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, and ApoAI at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Free Fatty Acid (FFA) at Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Lipoprotein(a) (Lp[a]) at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Percent Change From Baseline in ANGPTL3, TC, LDL-C, HDL-C, VLDL-C, Non-HDL-C, ApoB (ApoB-48, ApoB-100), ApoCIII, ApoAI, FFA, and Lp(a) at Primary Analysis Time Point

An ANCOVA model was performed on the log ratio of Primary Analysis Time Point to Baseline. The estimate of the log ratio was converted back to the original scale and percent change was calculated using formula: = (ratio of Primary Analysis Time Point to Baseline - 1) × 100.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Fasting Plasma Glucose at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Hemoglobin A1c (HbA1c) at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Fasting Insulin at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in and HOMA-IR at the Primary Analysis Time Point

HOMA-IR is a method used to quantify insulin resistance. HOMA-IR is expressed as the following: HOMA-IR = fasting serum insulin (μU/mL) \* fasting plasma glucose (mmol/L)/22.5. A negative change from Baseline indicates improvement. An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Fructosamine at Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Glycated Albumin at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Weight at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Percent Change From Baseline in Weight, SBP and DBP at Primary Analysis Time Point

An ANCOVA model was performed on the percent change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C6

Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Percent Change From Baseline in Hepatic Fat Fraction (HFF) by Magnetic Resonance Imaging-Derived Proton Density Fat Fraction (MRI-PDFF) at the Primary Analysis Time Point

An ANCOVA model was performed on the percent change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Percentage of Participants With HFF ≤ 8% by MRI-PDFF at the Primary Analysis Time Point

The percentage of participants who achieved HFF ≤ 8% at the Primary Analysis Time Point was compared between each ISIS 703802 treatment group and pooled placebo group using a logistic regression model.

Time frame: Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Fatty Liver Index (FLI) at the Primary Analysis Time Point

The FLI was calculated by the following formula: FLI =(e0.953×loge\[triglycerides\]+0.139× Body Mass Index \[BMI\]+0.718×loge Gamma- Glutamyl Transferase \[GGT\]+0.053×waistcircumference-15.745)/ (1 + e0.953×loge\[triglycerides\]+0.139×BMI+0.718×loge \[GGT\]+0.053×waistcircumference-15.745) × 100. An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Leptin at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Adiponectin at the Primary Analysis Time Point

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Subcutaneous Adipose Tissue (SAT) and Visceral Adipose Tissue (VAT) by Single Slice MRI at the Primary Analysis Timepoint

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Waist Circumference by Single Slice MRI at the Primary Analysis Timepoint

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Waist to Hip Ratio (WHR) at the Primary Analysis Timepoint

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Change From Baseline in Body Mass Index (BMI) at the Primary Analysis Timepoint

An ANCOVA model was performed on the change from Baseline to Primary Analysis Time Point.

Time frame: Baseline, Week 27 for Cohort A, and Week 25 for Cohorts B and C

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An AE was defined as any unfavorable and unintended sign (including a clinically-significant abnormal laboratory finding, for example), 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 were defined as adverse events that occurred after the first administration of study drug.

Time frame: Up to 13 weeks post treatment period (up to 39 weeks)