NCT02029482已完成1 期
Single-center, Double-blind, Placebo-controlled, Randomized, Parallel-group, Up-titration Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Increasing Doses of ACT-128800 in Healthy Male and Female Subjects
Actelion1 个研究点 分布在 1 个国家目标入组 16 人开始时间: 2010年4月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Change from baseline to Day 18 in systolic blood pressure
研究概览
简要总结
This was a single-center, randomized, double-blind, placebo-controlled, up-titration Phase 1 study. Sixteen subjects in two groups (at least 40% of subjects of either male or female sex), with 12 subjects in the active treatment group with an up-titration scheme from 10 to 100 mg, and 4 subjects in the placebo treatment group. Subjects were administered ascending doses of ACT-128800/placebo once daily for 3 days at each dose level: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg, and 100 mg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older 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.
- •Age between 18 and 65 years (inclusive) at screening.
- •Body mass index (BMI) between 18 and 30 kg/m^2 (inclusive).
- •Women of childbearing potential were required to have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to first drug intake and have agreed to use two methods of contraception from the screening visit until 2 months after study drug discontinuation.
- •Systolic blood pressure 100-150 mmHg, diastolic blood pressure 50-90 mmHg measured on the leading arm, and heart rate 50-95 beats per minute (inclusive) measured by electrocardiography (ECG) after 5 minutes in the supine position at screening.
- •ECG without clinically relevant abnormalities at screening.
- •Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening.
- •Negative results from urine drug screen at screening.
- •Ability to communicate well with the investigator and to understand and comply with the requirements of the study.
排除标准
- •ECG recording; PQ/PR interval > 200 ms at screening.
- •Pregnant or lactating women.
- •Known hypersensitivity to any excipients of the drug formulation.
- •Known hypersensitivity to beta2 adrenergic receptor agonists.
- •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).
- •Treatment with another investigational drug within 3 months prior to screening.
- •Excessive caffeine consumption, defined as ≥ 800 mg per day at screening. History or clinical evidence of any disease and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drug.
- •Smoking within the last month prior to screening.
- •Any immunosuppressive treatment within 6 weeks before study drug administration.
- •Previous treatment with any prescribed or over-the-counter medications (including herbal medicines such as St John's Wort) within 2 weeks prior to screening or 5 half-lives of the drug, whichever is longer.
- •Loss of 250 mL or more of blood within 3 months prior to screening.
- •Lymphopenia (< 1,000 cells/μL).
- •Viral, fungal, bacterial or protozoal infection within 4 weeks before study drug administration (e.g., active herpes and/or cytomegalovirus infection).
- •History or clinical evidence suggestive of active or latent tuberculosis at screening.
- •Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
- •Positive results from the human immunodeficiency virus serology at screening.
- •Forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 80% of the predicted value, or FEV1/FVC ratio < 0.7 at screening.
- •History of asthma or chronic obstructive pulmonary disease.
- •Any cardiac condition or illness (including ECG abnormalities) with a potential to increase the cardiac risk of the subject in the standard 12-lead ECG and 24-hour 3-lead Holter ECG at screening.
- •History of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
- •Familial history of sick-sinus syndrome.
- •History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening. Alcohol abuse is defined as regular weekly intake of more than 21 units.
- •Legal incapacity or limited legal capacity at screening.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect the subject's full participation in the study or compliance with the protocol.
研究组 & 干预措施
ACT-128800
Experimental
ACT-128800 tablets, once daily for 3 days at each dose level: 10 mg, 20 mg, 40 mg, 60 mg, 80 mg, and 100 mg.
干预措施: ACT-128800 (Drug)
Placebo
Placebo Comparator
Matching placebo tablets, once daily, for 18 days
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline to Day 18 in systolic blood pressure
时间窗: 18 days
Blood pressure was measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm right = writing with right hand). Measurements were recorded from the subject in the supine position after having rested for a 5-minute period.
Change from baseline to Day 18 in diastolic blood pressure
时间窗: 18 days
Blood pressure was measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm right = writing with right hand). Measurements were recorded from the subject in the supine position after having rested for a 5-minute period.
Change from baseline to Day 18 in pulse rate
时间窗: 18 days
Pulse rate was measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm right = writing with right hand). Measurements were recorded from the subject in the supine position after having rested for a 5-minute period.
Change from baseline to Day 18 in body temperature
时间窗: 18 days
Body temperature was measured in the supine position using the same thermometer throughout the study.
次要结局
- Change from baseline to Day 10 in mean absolute lymphocyte count(10 days)
- Area under the plasma concentration-time curve from time 0 to infinity (AUC0-infinity) of ACT-128800 on Day 18(18 days)
- Time to reach maximum plasma concentration (tmax) of ACT-128800 on Days 9 and 18(18 days)
- Change from baseline to Day 10 in mean T cell (Cluster of differentiation (CD) CD3+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean B cell (CD3-/CD19+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean natural killer (NK) cell (CD3-/CD56+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean natural killer T (NKT) cell (CD3+/CD56+) lymphocyte count(10 days)
- Terminal half-life (t1/2) of ACT-128800 on Day 18(18 days)
- Change from baseline to Day 10 in mean CD4+ T-helper cell (CD3+/CD4+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean T-cytotoxic cell (CD3+/CD8+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD4+T-naive cell (CD45RA+/chemokine receptor type 7 (CCR7+)) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD4+ T-central memory cell (CD45RA-/CCR7+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD4+ T-effector memory cell (CD45RA-/CCR7-) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD4+ T-effector cell (CD45RA+/CCR7-) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD8+ T-naive cell (CD45RA+/CCR7+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD8+ T-central memory cell (CD45RA-/CCR7+) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD8+ T-effector memory cell (CD45RA-/CCR7-) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean CD8+ T-effector cell (CD45RA+/CCR7-) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean T-regulatory cell (CD25+/Forkhead box P3 (Foxp3+)) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean skin-homing T-helper cell (Cutaneous lymphocyte antigen (CLA)+/integrin β7-) lymphocyte count(10 days)
- Change from baseline to Day 10 in mean gut-homing T-helper cell (CLA-/integrin β7+) lymphocyte count(10 days)
- Maximum plasma concentration (Cmax) of ACT-128800 on Days 9 and 18(18 days)
- Area under the plasma concentration-time curve from time 0 to 24 hours (AUC0-24) of ACT-128800 on Days 9 and 18(18 days)
研究者
研究点 (1)
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