A Randomized, Double-blind, Placebo-Controlled, Repeat-dose, Single-center Phase 1a Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
研究概览
简要总结
The purpose of this study to evaluate the safety, tolerability and pharmacokinetics (PK) of lanadelumab administered by Intravenous (IV) infusion in healthy adult volunteers.
详细描述
A Randomized, Double-blind, Placebo-Controlled, Repeat-dose, Single-center Phase 1a Study to Determine the Safety, Tolerability, and Pharmacokinetics of Lanadelumab Administered Intravenously in Healthy Adult Volunteer Subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 19 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy, adult, male or female, 19-55 years of age, inclusive, at screening.
- •Continuous non-smoker who has not used nicotine-containing products for at least 30 days prior to the first dosing and throughout the study, based on participant self-reporting.
- •Body mass index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 32.0 kilogram per square meter (kg/m^2) at screening.
- •Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or electrocardiograms (ECGs), per the investigator.
- •Male, or non-pregnant, non-lactating female who agrees to comply with any applicable contraceptive requirements of the protocol or females of non-childbearing potential.
- •Understands the study procedures in the informed consent form (ICF) and be willing and able to comply with the protocol.
排除标准
- •Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
- •History or presence of clinically significant medical or psychiatric condition or disease per the investigator.
- •History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study, per the investigator.
- •History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing per the investigator.
- •History or presence of hypersensitivity or idiosyncratic reaction to the study drug(s) or related compounds.
- •History or presence of any hematological, hepatic, respiratory, cardiovascular, renal, neurological or psychiatric disease, gall bladder removal, or current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or clinically significant clinical or laboratory assessments per the investigator.
- •Female participants with a positive pregnancy test or lactating.
- •Positive urine drug or alcohol results at screening.
- •Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- •Supine blood pressure is less than 90/40 millimetre of mercury (mmHg) or greater than 140/90 mmHg at screening.
- •Supine heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
- •Orthostatic vital sign results with a decrease in systolic greater than (>) 20 mmHg or decrease in diastolic > 10 mmHg and increase in pulse of > 20 beats per minute.
- •QTcF interval is > 450 milliseconds (msec) (males) or > 470 msec (females) or ECG findings are deemed abnormal with clinical significance at screening per the investigator.
- •Estimated creatinine clearance less than (<) 80 milliliters per minute (mL/min) at screening.
- •Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration. After randomization/dosing, a nonsteroidal anti-inflammatory drug may be administered at the discretion of the investigator. Hormone replacement therapy will also be allowed if the participant has been on the same stable dose for the immediate 3 months prior to first study drug administration.
- •Has been on a diet incompatible with the on-study diet, per the investigator, within the 30 days prior to the first dosing and throughout the study.
- •Donation of blood or significant blood loss within 56 days prior to the first dosing.
- •Plasma donation within 7 days prior to the first dosing.
- •Participation in another clinical study within 30 days or 5 half-lives prior to the first dosing. The 30-day window or 5 half-lives will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to Day 1 of the current study
研究组 & 干预措施
Lanadelumab 300 mg
Participants will receive single dose of lanadelumab 300 mg intravenous (IV) infusion on Day 1 followed by second dose on Day 4.
干预措施: Lanadelumab (Drug)
Placebo
Participant will receive single dose of lanadelumab matching placebo (normal saline) IV infusion on Day 1 followed by second dose on Day 4.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
时间窗: From the first dose of study treatment up to the end of study (Day 112)
12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. Any changes in ECG parameters that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
AUC0-last: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration for Lanadelumab
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
AUC0-last for lanadelumab was reported.
Terminal Half-Life (T1/2) of Lanadelumab in Plasma
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
T1/2 is defined as the time required for the concentration of the drug to reach half of its original value. T1/2 for lanadelumab was reported.
Tmax1: Minimum Observed Time to Reach the First Cmax1 for Lanadelumab
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
Tmax1 following the first IV dose for lanadelumab was reported.
Tmax2: Minimum Observed Time to Reach the Second Cmax2 for Lanadelumab
时间窗: Pre-dose (Day 4) up to 2592 hours post-dose
Tmax2 following the second IV dose for lanadelumab was reported.
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters
时间窗: From the first dose of study treatment up to the end of study (Day 112)
Clinical laboratory assessment included hematology, clinical chemistry, coagulation, and urinalysis. Any changes in clinical laboratory results that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant change from baseline in laboratory values were reported.
AUC0-inf: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity for Lanadelumab
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
AUC0-inf for lanadelumab was reported.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
时间窗: From the first dose of study treatment up to the end of study (Day 112)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant who has signed informed consent to participate in a study that did not necessarily have a causal relationship with the treatment. TEAEs were events that occurred on or after the date and time of administration of the first dose of study medication. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs were reported.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
时间窗: From the first dose of study treatment up to the end of study (Day 112)
Vital signs included blood pressure (systolic and diastolic), heart rate, and body temperature (oral). Any changes in vital signs that were deemed clinically significant were judged by the investigator. The number of participants with clinically significant change from baseline in vital signs were reported.
Cmax2: Maximum Observed Plasma Concentration Following the Second IV Dose for Lanadelumab
时间窗: Pre-dose (Day 4) up to 2592 hours post-dose
Cmax2 following the second IV dose for lanadelumab was reported.
Clearance (CL) of Lanadelumab in Plasma
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body. CL for lanadelumab was reported.
Cmax1: Maximum Observed Plasma Concentration Following the First IV Dose for Lanadelumab
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
Cmax1 following the first IV dose for lanadelumab was reported.
Vss: Volume of Distribution at Steady State in Plasma for Lanadelumab
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss for lanadelumab was reported.
First Order Elimination Rate Constant Associated With the Terminal (Log-linear) Portion of the Curve (Lambda z) of Lanadelumab
时间窗: Pre-dose (Day 1) up to 2664 hours post-dose
Lambda z of Lanadelumab was reported.
次要结局
未报告次要终点