A Phase 1, Single Ascending Oral Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of ASP3700 in Healthy Male Subjects, Including a Drug-drug Interaction Part With Itraconazole
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Safety as assessed by adverse events (Part 1)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending oral doses of ASP3700 in healthy male subjects. This study will also explore the effect of itraconazole (another drug) on the PK of ASP3700, as well as to evaluate the safety and tolerability of ASP3700 alone and in combination with itraconazole in healthy male subjects.
详细描述
This study consists of 2 parts: Part 1 is a single ascending dose study where subjects will receive either ASP3700 or matching placebo; Part 2 is a drug-drug interaction (DDI) open-label, crossover study comprised of 1 sequence with 2 investigational periods where subjects will receive ASP3700 alone and in combination with itraconazole.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Subject has a body mass index range of 18.5 - 30.0 kg/m
- •The subject weighs at least 50 kg.
- •Subject and his female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continue throughout the clinical study period and for 90 days after the final study drug administration.
- •Subject must not donate sperm starting at screening and throughout the clinical study period and for 90 days after the final study drug administration.
排除标准
- •Subject has a known or suspected hypersensitivity to ASP3700 (parts 1 and 2) or itraconazole (part 2 only) or significant adverse reactions to historical cannabinoid use or any components of the formulations used.
- •Subject has any of the liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, gamma-glutamyl transaminase, total bilirubin [TBL]) above the upper limit of normal (ULN). In such a case the assessment may be repeated once (upon admission to the clinical unit).
- •Subject has a history of a suicide attempt or suicidal behavior. Any recent suicidal ideation within the last 3 months or who are at significant risk to commit suicide, as judged by the Investigator using the C-SSRS (a level of 4 or 5) at screening or upon admission to the clinical unit.
- •Subject has any clinically significant abnormality following the Investigator's review of the physical examination, ECG and clinical study protocol-defined clinical laboratory tests at screening or upon admission to the clinical unit.
- •Subject has a pulse rate < 40 or > 90 beats per minute; mean SBP > 140 mmHg; mean DBP > 90 mmHg (vital signs measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse rate will be measured automatically) upon admission to the clinical unit.
- •Subject has a mean corrected QT interval using Fridericia's formula (QTcF) interval > 430 ms at day -
- •If the mean QTcF exceeds the limits above, 1 additional triplicate ECG can be taken.
- •Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit.
- •Subject has a history of drinking more than 21 units of alcohol per week (1 unit = 10 g pure alcohol = 250 mL of beer [5%] or 35 mL of spirits [35%] or 100 mL of wine [12%]) within 3 months prior to admission to the clinical unit.
- •Subject has consumed grapefruit, grapefruit-containing products or Seville orange-containing products within 72 hours prior to admission to the clinical unit.
研究组 & 干预措施
ASP3700 single ascending dose cohort
Part 1
干预措施: ASP3700 (Drug)
Placebo single ascending dose cohort
Part 1
干预措施: Placebo (Drug)
ASP3700 alone
Part 2
干预措施: ASP3700 (Drug)
ASP3700 and itraconazole
Part 2
干预措施: ASP3700 (Drug)
ASP3700 and itraconazole
Part 2
干预措施: itraconazole (Drug)
结局指标
主要结局
Safety as assessed by adverse events (Part 1)
时间窗: up to end of study visit (up to 16 days)
Safety as assessed by laboratory tests (Part 1)
时间窗: up to end of study visit (up to 16 days)
Laboratory tests includes the measurement of sex-hormone related biomarkers and exploratory renal biomarkers.
Pharmacokinetic parameter of itraconazole (plasma): Ctrough (Part 2)
时间窗: Days 3-13
Concentration immediately prior to dosing at multiple dosing
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUClast (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): CLR (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Renal clearance (CLR)
Safety as assessed by ARCI-49 (Part 1)
时间窗: Up to Day 2
Addiction Research Center Inventory (ARCI)-49 (49-item)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): t1/2 (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Terminal elimination half-life (t1/2)
Safety as assessed by vital signs (Part 1)
时间窗: up to end of study visit (up to 16 days)
Safety as assessed by electrocardiogram (ECG) measurements (Part 1)
时间窗: up to end of study visit (up to 16 days)
ECG measurements include routine 12-lead ECG, continuous cardiac monitoring (Holter ECG) and real-time cardiac monitoring (ECG telemetry)
Safety as assessed by C-SSRS (Part 1)
时间窗: Up to end of study visit (up to 16 days)
Columbia - Suicide Severity Rating Scale (C-SSRS)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUCinf (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Area under the concentration-time curve from time of dosing extrapolated to time infinity (AUCinf)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma):λz (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Terminal elimination rate constant (λz)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): MRT (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Mean residence time (MRT)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aeinf% (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Percentage of study drug excreted into urine from time of dosing extrapolated to time infinity (Aeinf%)
Safety as assessed by Bond and Lader VAS (Part 1)
时间窗: Up to Day 2
visual analogue scale (VAS)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): AUCinf (%extrap) (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Percentage of AUCinf due to extrapolation from tlast to time infinity (AUCinf \[%extrap\])
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): Cmax (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Maximum concentration (Cmax)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aelast (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Cumulative amount of study drug excreted into urine from time of dosing up to the collection time of the last measurable concentration (Aelast)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aeinf (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Cumulative amount of study drug excreted into urine from time of dosing extrapolated to time infinity (Aeinf)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): Vz/F (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Apparent volume of distribution during the terminal elimination phase after extravascular dosing (Vz/F)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (urine): Aelast% (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Percentage of study drug excreted into urine from the time of dosing up to the collection time of the last measurable concentration (Aelast%)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): tmax (Part 2)
时间窗: Days 1-7 (period 1) and Days 1-13 (period 2)
Time of maximum concentration (tmax)
Pharmacokinetic parameter of ASP3700 with and without itraconazole (plasma): tlag (Part 2)
时间窗: Day 1 (period 1 and 2)
Time prior to the time corresponding to the first measurable (nonzero) concentration (tlag)
Safety as assessed by orthostatic evaluation (or blood pressure change in orthostatic challenge test) (Part 1)
时间窗: Up to Day 7
次要结局
- Safety as assessed by adverse events, vital signs, orthostatic evaluation, laboratory tests, ECG measurements, C-SSRS, Bond & Lader VAS, ARCI-49 (Part 2)(Days 1-7 (period 1) and Days 1-13 (period 2) and at end of study visit (up to 22 days))
- Composite of pharmacokinetics of ASP3700: AUCinf, AUCinf(%extrap), AUClast, Cmax, CL/F, λz, MRT, tlag, tmax, t½, Vz/F (plasma) (Part 1)(up to Day 7)
- Title: Composite of pharmacokinetics of ASP3700: Aelast, Aeinf, Aelast%, Aeinf%, CLR (urine) (Part 1)(up to Day 7)