A Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Pelacarsen (ISIS 681257) in Healthy Japanese Participants

The purpose of the study is to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple subcutaneous (SC) doses of Pelacarsen (ISIS 681257) in healthy Japanese participants.

This was a randomized, placebo-controlled, participant and investigator-blinded, single ascending and multiple-dose study of Pelacrsen (ISIS 681257) in up to 29 healthy Japanese male and female participants. The study was conducted in two parts:1) Single ascending dose (SAD) including up to a 28-day screening period, a baseline period, dose with study drug on Day 1, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 90; 2) Multiple doses (MD) including up to a 28-day screening period, a baseline period, dose with study drug up to Day 85, a 2-day (48 hours) post-dose in-patient observation period, followed by an out-patient observation period up to Day 204.

In the SAD period, participants were randomized to receive single dose of Pelacarsen or placebo.

Upon completion of the SAD period participants were randomized to receive multiple doses of Pelacarsen.

Eligibility Criteria:
Inclusion Criteria:

1. Provided written informed consent (signed and dated) and any authorizations required by local law and was able to comply with all study requirements.
2. Male and female of first-, second- or third-generation Japanese participants.
3. Japanese healthy or obese male and female participants 18 to 65 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, ECG and laboratory tests at screening.
4. Participants weighed at least 45 kilograms (kg), healthy or obese with body mass index (BMI) ≤ 35.0 kilograms per meter square (kg/m\^2).
5. Participants had to have lipoprotein(a) (Lp\[a\]) ≥ 15 nanomole per liter (nmol/L) (8 milligram per deciliter \[mg/dL\]) at screening.

Exclusion Criteria:

1. Clinically significant abnormalities in medical history including acute coronary syndrome, major surgery within 3 months of screening, planned surgery that would have occurred during the study or physical examination or other screening results such as ECGs findings at screening.

Screening laboratory results as follows or any other clinically significant abnormalities in screening laboratory values that would have rendered a participant unsuitable for inclusion. If abnormal, the laboratory tests may have been repeated after consultation with the Sponsor Medical Monitor.

* Estimated glomerular filtration rate (eGFR) ˂ 60 milliliter per minute per 1.73 meter per square (mL/min/1.73m\^2) (as determined by the Chronic Kidney Disease-Epidemiological Collaboration \[CKD-EPI\] Equation).
* Urine protein-to-creatinine ratio (UPCR) ≥ 200 milligram per gram (mg/g) or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g.
* Alanine aminotransferase (ALT; serum glutamic pyruvic transaminase), aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase), bilirubin, alkaline phosphatase, serum creatinine, blood urea nitrogen \> 1.5 × upper limit of normal (ULN) at screening excluded a participant from participation in the study.
* Fasting blood glucose \> ULN. If elevated, hemoglobin A1c was checked and if \< 6%, the participant could have been enrolled.
* Platelet count \< 140,000 per microliter (/μL). 3. Active infection requiring systemic antiviral or antimicrobial therapy that would not have been completed prior to Day 1.