A Double-blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Ascending Multiple Oral Doses of ASP3652 in Healthy Young and Elderly Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- Body temperature
研究概览
简要总结
The study investigates how safe ASP3652 is and how well it is tolerated when taken as multiple doses. The study also assesses how quickly and to what extent it is absorbed and eliminated from the body. In addition, the effects of age and gender are investigated.
The study consists of two parts. In Part 1 four dose levels are administered to four separate groups initially. Two additional dosages are then investigated. Subjects receive either a once-daily dose (QD) or twice-daily dose (BID) of ASP3652 or placebo.
Part 2 is performed in one group of elderly healthy male or female (post-menopausal) subjects. Subjects receive either a twice daily dose (BID) of ASP3652 or placebo.
For both parts of the study, the subjects stay in the clinic for one period of 18 days.
详细描述
This is a Multiple Ascending Dose (MAD) study with two parts. Screening for both parts takes place between Days -28 and -3. Subjects are admitted to the clinic on Day -2, and discharged on Day 16. They return for an End of Study Visit (ESV) between 7 and 14 days after (early) discharge.
Part 1 evaluates the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ASP3652 following ascending multiple oral doses. The initially planned four dose levels or matching placebo are given to four separate groups. Thereafter two additional dosage levels are further investigated. All groups receive a single dose of ASP3652 administered in the morning of Day 1 and Day 14, and twice-daily doses administered from Day 2 to Day 13 under fasted conditions, except the last group which receives all dosages once daily from Day 1 to Day 14.
Part 2 evaluates the safety, tolerability, PK and PD of ASP3652 following ascending multiple oral doses in healthy elderly male and female subjects. This part contains a single, placebo-controlled group. All subjects receive twice daily doses and administration is based on the results of Part 1.
All subjects in both parts receive training for Neurocognitive Test Battery (NTB) and tests for monitoring of psychotropic effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Body Mass Index (BMI) between 18.5-30.0 kg/m2 for both male and female subjects.
- •Male subject is non-fertile, i.e. surgically sterilized or practices an adequate contraceptive method to prevent pregnancies.
- •Female subject is of non-child bearing potential, i.e. post menopausal, surgically sterilized, hysterectomy in medical history, or practices adequate (double barrier) non-hormonal contraceptive method to prevent pregnancies.
排除标准
- •Pregnant or breast feeding within 6 months before screening assessment.
- •Presence or history of any clinically significant psychiatric disorder such as mania, depression or schizophrenia.
- •Regular use of any inducer of liver metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.
研究组 & 干预措施
1: Placebo dose level
干预措施: Placebo (Drug)
2: ASP3652 lowest dose level twice daily
干预措施: ASP3652 (Drug)
3:ASP3652 low dose level twice daily
干预措施: ASP3652 (Drug)
4: ASP3652 medium dose level twice daily
干预措施: ASP3652 (Drug)
5: ASP3652 high dose level twice daily
干预措施: ASP3652 (Drug)
6: ASP3652 highest dose level once daily
干预措施: ASP3652 (Drug)
结局指标
主要结局
Body temperature
时间窗: Screening to 14 days after discharge
12 -lead Electrocardiogram (ECG)
时间窗: Screening to 14 days after discharge
PK profile in plasma for first dose measured by maximum plasma concentration (Cmax)
时间窗: Day 1 to Day 2
PK profile in plasma for first dose measured by apparent volume of distribution during the terminal phase (Vz/F)
时间窗: Day 1 to Day 2
PK profile in urine for first dose measured by percentage of unchanged drug excreted into the urine from time zero to time of last measurable concentration (Aelast%)
时间窗: Day 1 to Day 2
PK profile in plasma for last dose measured by tmax
时间窗: Day 14 to Day 16
PK profile in plasma for last dose measured by plasma concentration at the end of a dosing interval at steady state (Ctrough)
时间窗: Day 14 to Day 16
Nature, frequency and severity of adverse events
时间窗: Screening to 14 days after discharge
PK profile in urine for last dose measured by cumulative amount of drug excreted into urine over the time interval between consecutive dosing (Aetau)
时间窗: Day 14 to Day 16
Only for BID dosing
PK profile in urine for last dose measured by fraction of the drug excreted into urine (Aetau) over the time interval between consecutive dosing (Aetau%)
时间窗: Day 14 to Day 16
Only for BID dosing
PK profile in plasma for first dose measured by apparent total clearance of the drug from plasma after oral administration (CL/F)
时间窗: Day 1 to Day 2
Routine safety laboratory tests
时间窗: Screening to 14 days after discharge
Holter ECG
时间窗: Day -1 and Day14
Pharmacokinetic (PK) profile in plasma for first dose measured by area under the plasma concentration - time curve from time zero to infinity (AUCinf)
时间窗: Day 1 to Day 2
PK profile in plasma for first dose measured by area under the plasma concentration - time curve from time zero to time of last measurable concentration (AUClast)
时间窗: Day 1 to Day 2
PK profile in plasma for first dose measured by time to attain Cmax (tmax)
时间窗: Day 1 to Day 2
PK profile in urine for first dose measured by cumulative amount of unchanged drug excreted into the urine from time zero to time of last measurable concentration (Aelast)
时间窗: Day 1 to Day 2
PK profile in urine for first dose measured by cumulative amount of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf)
时间窗: Day 1 to Day 2
PK profile in urine for first dose measured by percentage of unchanged drug excreted into the urine from time zero to infinity after single dose (Aeinf%)
时间窗: Day 1 to Day 2
PK profile in urine for last dose measured by percentage of unchanged drug excreted into the urine from 0 to 24 hours (Ae0-24%)
时间窗: Day 14 to Day 16
PK profile in plasma for first dose measured by absorption lag time (tlag)
时间窗: Day 1 to Day 2
Physical examination and vital signs
时间窗: Screening to 14 days after discharge
Monitoring of psychotropic / cannabinoids-like effects
时间窗: Screening to 14 days after discharge
Neurocognition Test Battery (NTB)
时间窗: Screening to 14 days after discharge
Examination for skin lesions
时间窗: Screening to 14 days after discharge
PK profile in plasma for first dose measured by elimination half-life (t½)
时间窗: Day 1 to Day 2
PK profile in urine for first dose measured by renal clearance of the drug from plasma (CLR)
时间窗: Day 1 to Day 2
PK profile in plasma for last dose measured by area under the plasma concentration- time curve from the time of dosing up to 24 hours (AUC0-24)
时间窗: Day 14 to Day 16
Only for BID dosing
PK profile in plasma for last dose measured by Cmax
时间窗: Day 14 to Day 16
PK profile in plasma for last dose measured by CL/F
时间窗: Day 14 to Day 16
PK profile in plasma for last dose measured by accumulation ratio (Rac)
时间窗: Day 14 to Day 16
PK profile in plasma for last dose measured by Peak Trough Ratio (PTR)
时间窗: Day 14 to Day 16
PK profile in urine for last dose measured by CLR
时间窗: Day 14 to Day 16
Only for BID dosing
PK profile in urine for last dose measured by cumulative amount of unchanged drug excreted into the urine from 0 to 24 hours (Ae0-24)
时间窗: Day 14 to Day 16
Only for BID dosing
PK profile in plasma for last dose measured by area under the plasma concentration - time curve between consecutive dosing (AUCtau)
时间窗: Day 14 to Day 16
Only for Bis in die (twice daily) (BID) dosing
PK profile in plasma for last dose measured by t½
时间窗: Day 14 to Day 16
PK profile in plasma for last dose measured by Vz/F
时间窗: Day 14 to Day 16
次要结局
- Pharmacodynamics measured by levels of palmitoyl-ethanolamide (PEA) in plasma and seminal fluid (exploratory)(Day -2 or -1 and day 11, 12 or 13)
- Assessment of Pharmacodynamics measured by intraocular pressure (IOP) (exploratory)(Day -1 to Day 15)
- Pharmacodynamics measured by levels of oleoyl-ethanolamide (OEA) in plasma and seminal fluid (exploratory)(Day -2 or -1 and day 11, 12 or 13)
- Assessment of Pharmacodynamics measured by Ex vivo enzyme activity in mononuclear cells(Day -1 to Day 16)
- Pharmacodynamics measured by levels of arachidonoyl-ethanolamide (AEA) in plasma and seminal fluid (exploratory)(Day -2 or -1 and day 11, 12 or 13)