A Single-center, Open-label, Two-period, Two-treatment, Crossover, Single-dose Study in Healthy Female and Male Subjects to Assess the Pharmacokinetics, Safety, and Tolerability of Two Different Formulations of ACT-129968
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t).
研究概览
简要总结
To explore the pharmacokinetics (PK) of a single dose of two different formulations of ACT-129968, i.e., tablet versus capsule and to evaluate the safety and tolerability of a single dose of two different formulations of ACT-129968, i.e., tablet versus capsule.
详细描述
A total of 10 female and 10 male healthy subjects will be enrolled and will attend two treatment periods, separated by a 7-9 day washout. Over these two periods, two formulations of ACT-129968 (Treatment A: two capsules, 250 mg each; Treatment B: one tablet, 500 mg) will be administered in the sequence A/B or B/A to 10 subjects (5 females and 5 males) per sequence as determined by randomization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent in the local language prior to any study-mandated procedure.
- •Women must have
- •a negative serum pregnancy test at screening and
- •a negative urine pregnancy test pre-dose on Day-1 of each treatment period.
- •Women of childbearing potential must consistently and correctly use (from screening, during the entire study, and for at least 28 days after last study drug intake) a reliable method of contraception with a failure rate of < 1% per year, be sexually inactive, or have a vasectomized partner.
- •Women not of childbearing potential are defined as post-menopausal (i.e., spontaneous amenorrhea for at least 1 year without an alternative medical cause) or surgically or naturally sterile.
- •No clinically significant findings on the physical examination at screening.
- •Body mass index (BMI) of 18.0 to 28.0 kg/m^2 (inclusive) at screening.
- •Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and pulse rate (PR) 45-90 bpm (inclusive), measured on the dominant arm (dominant arm = writing arm) after 5 minutes in the supine position at screening.
- •12-lead electrocardiogram (ECG) without clinically relevant abnormalities, measured after 5 minutes in the supine position at screening.
- •Hematology, clinical chemistry, and urinalysis test results not deviating from the normal range to a clinically relevant extent at screening.
- •Negative results from urine drug screen and breath alcohol test at screening and on admission to the unit (Day-1) in Period 1 and Period
- •Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.
排除标准
- •Pregnant or lactating women.
- •Known allergic reactions or hypersensitivity to any excipient of the drug formulation(s).
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendectomy and herniotomy allowed, cholecystectomy not allowed).
- •Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
- •History or clinical evidence of allergic rhinitis or asthma.
- •Veins unsuitable for intravenous puncture on either arm (e.g., veins that are difficult to locate, access, or puncture, veins with a tendency to rupture during or after puncture).
- •Previous exposure to the study medication.
- •Treatment with another investigational drug within 3 months prior to screening or participation in more than four investigational drug studies within 1 year prior to screening.
- •History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
- •Excessive caffeine consumption, defined as 800 mg per day at screening.
- •Alcohol consumption of > 21 units/week or > 3 units/day.
- •Smoking within 3 months prior to screening.
- •Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to first study drug administration.
- •Loss of 250 mL or more of blood within 3 months prior to screening.
- •Positive results from the hepatitis serology (Hepatitis B surface antigen and anti-hepatitis C virus), except for vaccinated subjects or subjects with past but resolved hepatitis (defined as positive finding for antibodies but negative findings for antigens), at screening.
- •Positive results from the human immunodeficiency virus serology at screening.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- •Legal incapacity or limited legal capacity at screening.
研究组 & 干预措施
ACT-129968 tablet/capsules
Subjects attend two treatment periods. In the first treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as a tablet (1 tablet, 500 mg) in the fasted state. In the second treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as capsules (2 capsules, 250 mg each) in the fasted state. There is a 7-9 day washout period between the first treatment period and the second treatment period.
干预措施: ACT-129968 500 mg tablet (Drug)
ACT-129968 tablet/capsules
Subjects attend two treatment periods. In the first treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as a tablet (1 tablet, 500 mg) in the fasted state. In the second treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as capsules (2 capsules, 250 mg each) in the fasted state. There is a 7-9 day washout period between the first treatment period and the second treatment period.
干预措施: ACT-129968 250 mg capsule (Drug)
ACT-129968 capsules/tablet
Subjects attend two treatment periods. In the first treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as capsules (2 capsules, 250 mg each) in the fasted state. In the second treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as a tablet (1 tablet, 500 mg each) in the fasted state. There is a 7-9 day washout period between the first treatment period and the second treatment period.
干预措施: ACT-129968 500 mg tablet (Drug)
ACT-129968 capsules/tablet
Subjects attend two treatment periods. In the first treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as capsules (2 capsules, 250 mg each) in the fasted state. In the second treatment period subjects receive a single, oral dose of ACT-129968 500 mg administered as a tablet (1 tablet, 500 mg each) in the fasted state. There is a 7-9 day washout period between the first treatment period and the second treatment period.
干预措施: ACT-129968 250 mg capsule (Drug)
结局指标
主要结局
The area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-t).
时间窗: Up to 48 h in each treatment period (1 and 2)
The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.
The maximum plasma concentration (Cmax)
时间窗: Up to 48 h in each treatment period (1 and 2)
The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.
The area under the plasma concentration-time curve from zero to infinity (AUC0-infinity).
时间窗: Up to 48 h in each treatment period (1 and 2)
The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.
The time to reach maximum plasma concentration (tmax)
时间窗: Up to 48 h in each treatment period (1 and 2)
The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.
The terminal elimination half-life (t½)
时间窗: Up to 48 h in each treatment period (1 and 2)
The plasma PK parameters for ACT-129968 will be derived by non-compartmental analysis of the plasma concentrationtime profiles.
次要结局
- Change from baseline to EOS for virus serology(Up to 13 days)
- Change from baseline to each time point of measurement during each treatment period and to EOS in supine blood pressure(Up to 13 days)
- Body weight at baseline and end of study visit(Up to 13 days)
- Change from baseline to each time point of measurement during each treatment period and to EOS in ECG variables(Up to 13 days)
- Change from baseline to EOS for hematology(Up to 13 days)
- Change from baseline to EOS for clinical chemistry(Up to 13 days)
- Change from baseline to EOS for pregnancy serum test(Up to 13 days)
- Number of patients with treatment-emergent ECG abnormalities for each treatment period(from study drug administration on Day 1 up to 48 hours post-dose)
- Change from baseline to each time point of measurement during each treatment period and to EOS in pulse rate(Up to 13 days)
- Number of patients with AEs leading to premature discontinuation of study drug(Entire duration of study)
- Number of patients with treatment-emergent physical examination abnormalities at EOS(Up to 13 days)
- Number of patients with treatment-emergent AEs and SAEs for each treatment period(from study drug administration on Day 1 up to 48 hours post-dose)