临床试验/NCT02368912

NCT02368912已完成1 期

A Double Blind, Randomized, Placebo-controlled, Ascending Single and Multiple Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP1707 in Healthy Young and Elderly Male Subjects and in Healthy Pre-menopausal Female Subjects Including an Open-label Comparison of Pharmacokinetics Under Fasted and Fed Conditions in Healthy Young Male Subjects

Astellas Pharma Europe B.V.1 个研究点分布在 1 个国家目标入组 176 人开始时间: 2010年6月最近更新: 2015年2月23日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Astellas Pharma Europe B.V.
入组人数: 176
试验地点: 1
主要终点: Safety assessed by nature, frequency and severity of adverse events

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This study consists of four parts:

Part 1 is a randomized, double-blind, placebo-controlled, single ascending dose study in healthy young male subjects to evaluate the safety, tolerability pharmacokinetics (PK) and effect on certain hormones and if possible to determine the highest well-tolerated dose of ASP1707 in healthy young male subjects under fasted conditions.

Part 2 is an open label, randomized crossover, single dose study to determine the effect of food on the pharmacokinetics of ASP1707and effect on certain hormones in healthy young male subjects.

Part 3 is a randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, tolerability and pharmacokinetics (PK) of ASP1707 in healthy elderly men and healthy premenopausal females, and to determine the effect on certain hormones in males. Age and gender is also evaluated.

Part 4 is a randomized, double-blind, placebo-controlled, parallel, multiple dose study to evaluate the safety, tolerability and PK of ASP1707, and its effect on certain hormones in healthy pre-menopausal female subjects.

详细描述

Part 1 comprises 7 dose groups of 8 healthy young male subjects. ASP1707 or matching placebo ( 3 to 1 ratio) is given as a single dose under fasted conditions.

The first group receives the lowest dose while the last group receives the highest dose.

Part 2 (Food-Effect) The group consists of 12 healthy young male subjects who receive two separate doses of ASP1707 under fasted or fed conditions. Half of the subjects are dosed first under fasted condition and half of them had first an FDA high-fat breakfast. Subjects receive the alternate treatment on the second occasion. Dosing is separated by at least 7 days or 7 times t1/2 (terminal elimination half-life) as assessed from Part 1.

Part 3 Comprises 4 dose groups of 12 healthy elderly men each, and two groups of 12 healthy premenopausal women. The latter are dosed ASP1707 or placebo in parallel to the 4 male groups. Subjects are fasted or fed depending on observations from Part 2.

Dose levels are defined after evaluating interim safety, tolerability and PK and PD results from Part 1. A lower maximum dose is used in women than in men, based on preclinical data. Dose escalation in the men is independent from dose escalation in the women. Women and men receive once-daily dosing;

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: 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

•Parts 1 & 2:
•Healthy young male subject aged 18 to 45 years inclusive
•Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m
•Male subjects must be non-fertile, or must practice an adequate contraceptive method to prevent pregnancies.
•Healthy elderly male subject aged 55 years or older, or healthy pre-menopausal female subject aged 18 to 45 inclusive.
•Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m
•Male subject must be non-fertile, or must practice adequate contraceptive methods.
•Female subjects must be of non-child bearing potential, i.e. surgically sterilized or practice adequate (double barrier) non-hormonal contraceptive methods.
•Healthy pre-menopausal female subject aged 18 to 45 inclusive.
•Body Mass Index more than or equal to 18.5 and less than 30.0 kg/m
•Female subjects must be of non-child bearing potential, i.e. surgically sterilized or practice adequate contraceptive methods.
•Females having a regular menstruation cycle with a duration between 25 up to 30 days.

排除标准

•Parts 1 & 2:
•Male subjects with out-of-range Testosterone levels in serum at screening.
•Subjects with any history of cancer.
•Any of the liver function tests (i.e. ALT and AST) above the upper limit of normal.
•A QTc interval of > 430 ms after repeated measurements.
•Regular use of any inducer of metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit.
•Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+
•Pregnancy within 6 months before screening assessment or breast feeding 3 months before screening.
•Male subjects with out-of-range T levels in serum at screening.
•Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+
•Pregnancy within 6 months before screening assessment or breast feeding 3 months before screening.
•Use of any hormonal interfering contraceptives in the 3 months before admission (for 3 consecutive menstruation cycles) OR any evidence of unovulatory menstrual cycles.
•Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2.

干预措施: Placebo parallel multiple dose (Drug)

结局指标

主要结局

Safety assessed by nature, frequency and severity of adverse events

时间窗: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)

Respectively Part 1 and Part 3

PK of ASP1707 measured by time to reach quantifiable concentrations (tlag) in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by Cmax in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by amount excreted unchanged into urine (Ae) from time of dosing until last measurable concentration (Aelast) in urine

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by Ae in % extrapolated to time infinity (Aeinf%) in urine

时间窗: Pre-dose (Day 1) to Day 5

Part 2

Safety assessed by physical examination

时间窗: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)

Respectively Part 1 and Part 3

Safety assessed by safety laboratory tests

时间窗: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)

Respectively Part 1 and Part 3, Biochemistry, hematology, and urinalysis

Safety assessed by 12 lead electrocardiogram (ECG)

时间窗: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)

Respectively Part 1 and Part 3

Safety assessed by vital signs

时间窗: Screening to End of Study Visit (ESV) (up to Day 19 and up to Day 39)

Respectively Part 1 and Part 3. Vital signs include blood pressure and pulse.

Pharmacokinetics (PK) of ASP1707 measured by area under the plasma concentration - time curve (AUC) extrapolated to time = infinity (AUCinf) in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by time to attain maximum concentration (tmax) in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by renal clearance (CLR) in urine

时间窗: Pre-dose (Day 1) to Day 5

Part 2

Safety assessed by continuous cardiac monitoring (Holter)

时间窗: Days -1 and 21

Part 3

PD of ASP1707 - maximal duration within therapeutic range

时间窗: Pre-dose to Day 26

Part 4, period 2. E2 levels

PK of ASP1707 measured by area under the plasma concentration-time curve (AUC) to time from the time of dosing to the last measurable concentration (AUClast) in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by terminal elimination half-life (t1/2) in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by apparent volume of distribution (Vz/F) in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by apparent clearance (CL/F) in plasma

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by Ae extrapolated to time = infinity (Aeinf) in urine

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PK of ASP1707 measured by Ae in % up to the collection time of the last measurable concentration (Aelast%) in urine

时间窗: Pre-dose (Day 1) to Day 5

Part 2

PD of ASP1707 measured by average concentration (Cavg, day 7-15) in plasma

时间窗: Pre-dose to Day 26

Part 4, period 1, 2 and 3. E2, FSH and LH levels

PD of ASP1707 measured by average concentration (Cavg, day 23-26) in plasma

时间窗: Pre-dose to Day 26

Part 4, period 2. E2, FSH and LH levels

PD of ASP1707 - Time of onset therapeutic range

时间窗: Pre-dose to Day 26

Part 4, period 2. E2 levels

Pharmacodynamics (PD) of ASP1707 measured by Cmax in plasma

时间窗: Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3

Part 4, period 1, 2 and 3. Estradiol (E2), Follicle-stimulating hormone (FSH) and Luteinizing Hormone (LH) levels

PD of ASP1707 measured by tmax in plasma

时间窗: Day -1 to day 15 for period 1, Day 7 to Day 15 for periods 2 and 3

Part 4, period 1, 2 and 3. E2, FSH and LH levels

PD of ASP1707 measured by average concentration (Cavg, day 5-19) in plasma

时间窗: Pre-dose to Day 26

Part 4, period 3. E2, FSH and LH levels

PD of ASP1707 - Time of start menstruation after last dose of study drug

时间窗: Pre-dose to Day 26

Part 4, period 3

PD of ASP1707 - total duration within therapeutic range (20-50 pg/mL)

时间窗: Pre-dose to Day 26

Part 4, period 2. E2 levels

PD of ASP1707 - Time of offset therapeutic range

时间窗: Pre-dose to Day 26

Part 4, period 2. E2 levels

次要结局

PK profile of ASP1707 in plasma and urine for Part 4(Pre-dose (Day 23) to Day 25)
PD profile of ASP1707 for Part 3(Pre-dose (Day 1) to Day 39)
Safety profile assessed by nature, frequency and severity of adverse events, physical examination, vital signs, safety laboratory tests and 12 lead ECG(Screening to End of Study Visit (ESV) (Up to 31 days and up to 62 days))
PK profile of ASP1707 in plasma and urine for Part 3(Pre-dose (Day 1) to Day 25)
PD profile of ASP1707 for Part 1 and Part 2(Pre-dose (Day 1) to Day 12-19)
PK profile of ASP1707 in plasma and urine for Part 1(Pre-dose (Day 1) to Day 5)

研究者

发起方

Astellas Pharma Europe B.V.

申办方类型

Industry

责任方

Sponsor

研究点 (1)

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