Pharmacokinetic Study of KHK7580 in Healthy Adult Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Plasma KHK7580 concentration at each time point
研究概览
简要总结
The primary objective is to evaluate the pharmacokinetic profile of KHK7580 in Chinese healthy adult volunteers. The secondary objective is to evaluate its safety and pharmacodynamics.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 39 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Personally submitted written voluntary informed consent to participate in the study;
- •Chinese adult ≥20 and <40 years of age at informed consent;
- •BMI ≥18.5 kg/m2 and <25.0 kg/m2 at screening.
排除标准
- •Subjects must be excluded from the study if they meet any of the following criteria:
- •Subjects with present illness requiring treatment;
- •Subjects in whom the serum Ca concentration, as measured at pretreatment (screening and Day -1) blood chemistry examination, is below the lower limit of the in-house reference value;
- •Subjects in whom a clinically significant abnormality in the crystalline lens is noted at a pre-study ophthalmological examination;
- •Subjects with urinary tract lithiasis or its past history;
- •Subjects with convulsive seizure or its past history;
- •Subjects with digestive system disorder (peptic ulcer, reflux esophagitis, etc.) or its past history (in this regard, however, a past history of appendicitis is acceptable);
- •Subjects with mental disorder or its past history;
- •Subjects who have alcohol/drug dependence or tested positive for any of the drug abuse test items;
- •Subjects with symptomatic allergy disease;
- •Subjects with drug allergy or its past history;
- •Subjects with a past history or family history of congestive heart failure, hypokalemia, or long QT syndrome; Protocol Number: 7580-202 (ver. 1.2) Date: 25 April, 2019 CONFIDENTIAL 7
- •Subjects in whom a 12-lead ECG tracing before initiation of study drug administration showed, in the judgment of the investigator or subinvestigator, a clinically significant abnormality or an electrocardiographic waveform shape unfit for QT interval measurement;
- •Subjects who tested positive for any of the infection test items;
- •Subjects who have used any drugs (including over-the-counter drugs, external preparations, vitamin preparations, and herbal preparations) within 2 weeks before initiation of study drug administration;
- •Subjects who have smoked a cigarette or used a treatment aid to smoking cessation (including nicotine-containing product chewing/ingestion and nicotine-containing patches) within 2 weeks before initiation of the study drug administration;
- •Subjects who have participated in a clinical study of a drug and practically received the drug within 4 months before initiation of the study drug administration;
- •Subjects who, within 3 months before initiation of the study drug administration, have been hospitalized, undergone surgery, or undergone collection of at least 200 mL of blood (including blood donation and blood component donation);
- •Subjects who did not consent to use an effective contraceptive (e.g., use of condoms) alone or in combination between the day of hospitalization and 3 months after the end of the study drug administration;
- •Pregnant, lactating, possibly pregnant subjects/women (subjects/women of childbearing potential with positive pregnancy test at screening or Day -1, or with negative pregnancy test at screening and Day -1 not using any contraceptive methods), or unwilling to use adequate contraception according to the physician's instructions. Amenorrhea for ≥12 months after the last menstrual period without an alternative medical cause is considered as non-childbearing potential;
- •Prior exposure to KHK7580;
- •Other conditions unfit for participation in this study at the discretion of the investigator or subinvestigator.
研究组 & 干预措施
Single dose administration of 1mg KHK7580
干预措施: 1mg KHK7580 (Drug)
Single dose administration of 3mg KHK7580
干预措施: 3mg KHK7580 (Drug)
Single dose administration of 6mg KHK7580
干预措施: 6mg KHK7580 (Drug)
Single dose administration of 12mg KHK7580
干预措施: 12mg KHK7580 (Drug)
Multiple dose administration of 6mg KHK7580 for 8days
干预措施: 6mg KHK7580 for 8days (Drug)
结局指标
主要结局
Plasma KHK7580 concentration at each time point
时间窗: pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort
Apparent systemic clearance (CL/F) of KHK7580
时间窗: pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort
Time to Reach Maximum Observed Plasma Concentration (Tmax) of KHK7580
时间窗: pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort
Maximum Observed Plasma Concentration (Cmax) of KHK7580
时间窗: pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort
Area under the plasma concentration-time curve from time 0 to the time of last quantifiable concentration (AUC0-t) of KHK7580
时间窗: pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of KHK7580
时间窗: pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort
Plasma Half-Life (t1/2) of KHK7580
时间窗: pre-dose, 0.25, 0.5,1,2,3,4,6,8,12,24,36,48,72 hours post-dose for single dose cohort; pre-dose, 0.25, 0.5,1,2,3,4,8,12,16 hours post dose of Day -1 and pre-dose, 2,4,8,12,16,24,36,48,72,96 hours post-dose of Day 8 for multiple dose cohort
次要结局
- QTcF([Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12)
- QTcB([Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12)
- intact PTH level([Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12)
- serum P level([Single dose] baseline to Day 4; [Multiple dose] baseline to Day 12)
- Incidence of treatment emergent adverse events (TEAEs)(Dosing to study completion)