PA-001 - A Phase 1, Double Blind, Randomized, Placebo Controlled, Single and Multiple Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics in Healthy and Elderly Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events after single and multiple IV dosed of PA-001 in healthy subjects
研究概览
简要总结
This was a double blind, randomized, placebo controlled, single and multiple IV dose study conducted in 2 parts, single ascending dose and multiple ascending doses parts. The principal aim of this study was to obtain safety and tolerability data when PA-001 is administered IV as single and multiple doses to healthy subjects. This information, together with the PK data, will help establish the doses and dosing regimen suitable for future studies in patients. The study also investigated the effects of age on the PK of PA-001 prior to patient studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Groups of healthy subjects: Males or females, of any race, between 18 and 65 years of age, inclusive.
- •Group(s) of elderly subjects: Males or females, of any race, > 65 years of age.
- •Body mass index between 18.0 and 32.0 kg/m2, inclusive.
- •In good health, or have stable, chronic, non life threatening medical conditions, determined by no clinically significant findings
- •Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
- •Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
排除标准
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder that, in the opinion of the investigator (or designee), could impact subject safety or the objectives of the study.
- •Have signs and symptoms of any other liver disease, except nonalcoholic fatty liver disease, or any of the following, as determined from clinical laboratory evaluations:
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, as determined by the investigator (or designee).
- •Positive hepatitis panel or positive human immunodeficiency virus test.
- •Positive SARS-CoV-2 test at screening or check in.
- •Have signs which shows something was not right in the ECG or history of additional risk factors for torsades de pointes.
- •Administration of a COVID 19 vaccine in the past 30 days prior to dosing.
- •Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 30 days or 5 half lives of that drug prior to dosing, whichever is longer.
- •Subjects who, in the opinion of the investigator (or designee), should not participate in this study.
研究组 & 干预措施
MAD
Multiple-dose, sequential-group of PA-001
干预措施: PA-001 (Drug)
SAD
Single-dose, sequential-group of PA-001
干预措施: PA-001 (Drug)
结局指标
主要结局
Incidence and severity of adverse events after single and multiple IV dosed of PA-001 in healthy subjects
时间窗: For approx. 8 weeks
An adverse event (AE) was any untoward medical occurrence in a subject, temporally associated with the use of study intervention. A serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect and resulted in an important medical events. TEAEs were defined as events that occurred after start of treatment.
Incidence of laboratory abnormalities (hematology, clinical chemistry and urinalysis test)
时间窗: For approx. 8 weeks
Clinical hematology parameters included: hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, mean cell hemoglobin (MCH), MCH concentration and mean cell volume. Chemistry parameters included: blood urea nitrogen, creatinine, estimated glomerular filtration rate, glucose, calcium, sodium, potassium, chloride, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, bicarbonate, gamma-glutamyl transferase, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, B-type natriuretic peptide, highly sensitive troponin T and lactate dehydrogenase. Urinalysis parameters included: potential of hydrogen (pH), glucose, protein, blood, ketones, nitrite, leukocyte esterase, bilirubin, color and appearance, specific gravity.
12-lead electrocardiogram parameters
时间窗: For approx. 8 weeks
A 12-lead ECG was performed. Clinically meaningful findings in ECG assessments were based on the investigator's judgment
次要结局
- AUCinf of PA-001 in plasma following single and multiple IV dose(SAD: predose to 48 hours after start of infusion, MAD: predose to 48 hours after start of the last infusion)
- AUClast of PA-001 in plasma following single and multiple IV dose(SAD: predose to 48 hours after start of infusion, MAD: predose to 48 hours after start of the last infusion)
- Cmax of PA-001 in plasma following a single and multiple IV dose(SAD: predose to 48 hours after start of infusion, MAD: predose to 48 hours after start of the last infusion)
- T1/2 of PA-001 in plasma following single and multiple IV dose(SAD: predose to 48 hours after start of infusion, MAD: predose to 48 hours after start of the last infusion)
- Percent Urinary Recovery of PA-001 following single IV dose(SAD only, predose to 48 hours after start of infusion)