A Randomized Double-blind, Placebo-controlled, Non-confirmatory Study to Assess Safety, Tolerability, PK, and PD of Single Ascending and Multiple Doses of ISIS 681257 in Healthy Japanese Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- MAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provided written informed consent (signed and dated) and any authorizations required by local law and was able to comply with all study requirements.
- •Male and female of first-, second- or third-generation Japanese participants.
- •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.
- •Participants weighed at least 45 kilograms (kg), healthy or obese with body mass index (BMI) ≤ 35.0 kilograms per meter square (kg/m^2).
- •Participants had to have lipoprotein(a) (Lp[a]) ≥ 15 nanomole per liter (nmol/L) (8 milligram per deciliter [mg/dL]) at screening.
排除标准
- •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).
- •Active infection requiring systemic antiviral or antimicrobial therapy that would not have been completed prior to Day 1.
研究组 & 干预措施
SAD: Placebo
Single dose of Pelacarsen-matching placebo administered by SC injection on Day 1 of single-dose treatment period.
干预措施: Placebo (Drug)
SAD: Pelacarsen 20 milligrams (mg)
Single dose of Pelacarsen, 20 mg, administered by SC injection on Day 1 of single-dose treatment period.
干预措施: Pelacarsen (Drug)
SAD: Pelacarsen 40 mg
Single dose of Pelacarsen, 40 mg, administered by SC injection on Day 1 of single-dose treatment period.
干预措施: Pelacarsen (Drug)
SAD: Pelacarsen 80 mg
Single dose of Pelacarsen, 80 mg, administered by SC injection on Day 1 of single-dose treatment period.
干预措施: Pelacarsen (Drug)
MD: Placebo
Multiple doses of Pelacarsen-matching placebo administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period.
干预措施: Placebo (Drug)
MD: Pelacarsen 80 mg
Multiple doses of Pelacarsen, 80 mg, administered by SC injection every 4 weeks, on Days 1, 29, 57 and 85 of multiple-dose treatment period.
干预措施: Pelacarsen (Drug)
结局指标
主要结局
MAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters
时间窗: Up to Day 204
MAD: Percentage of Participants With Serious Adverse Events
时间窗: Up to Day 204
SAD: Percentage of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Evaluation Parameters
时间窗: Up to Day 90
SAD: Percentage of Participants With Serious Adverse Events
时间窗: Up to Day 90
SAD: Percentage of Participants With Adverse Events
时间窗: Up to Day 90
MAD: Percentage of Participants With Adverse Events
时间窗: Up to Day 204
次要结局
- Maximum Observed Drug Concentration (Cmax) in Plasma After Single Ascending Dose of Pelacarsen(Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose)
- Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Single Ascending Dose of Pelacarsen(Day 1: Pre-dose; 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 up to 168 hours post-dose)
- Maximum Observed Drug Concentration (Cmax) in Plasma After Multiple Doses of Pelacarsen(Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose)
- Area Under Curve (AUC) From Time Zero to the Last Quantifiable Concentration (AUClast) in Plasma After Multiple Doses of Pelacarsen(Days 1 and 85: Pre-dose; 1, 2, 4, 8, 24 up to 168 hours post-dose)