First in Human Dose Ascending, Randomized, Placebo-Controlled Clinical Trial to Assess Tolerability and Pharmacokinetics of ApTOLL in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events as assessed by CTCAE v4.0
研究概览
简要总结
This is a Phase I, first-in-human, dose ascending, randomized, placebo-controlled clinical study to assess the tolerability and pharmacokinetics of ApTOLL in healthy volunteers. ApTOLL is an aptamer able to antagonize TLR4 receptor and, therefore, to reduce the inflammatory response.
详细描述
This Phase I clinical trial is divided in two parts: the first part (part A) is a single dose escalation study and the second (part B) is a multiple dose study. Both are performed in healthy volunteers.
- First part: a single dose, i.v. administration (slow infusion), dose escalation with a maximum of 7 single dose levels, randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.
- Second part: a multiple dose, i.v. administration (slow infusion), randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.
The main objectives of this study are:
- To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after single dose administration in fasting conditions, following an ascending dosing scheme.
- To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after multiple dose administration in fasting conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female subjects (women without possibility of becoming pregnant) willing and able to give their written consent to participate in the trial.
- •Healthy subjects aged within: 18 to 55 years (limits included).
- •Clinical history and physical examination results within normality.
- •Vital signs and electrocardiogram without clinically significant pathologic abnormalities and with QTc (Corrected QT space) values lower than 450 ms.
- •Body weight between 65 and 85 kg, inclusive.
- •BMI (Body Mass Index) between 19.0 and 30.0 kg/m
- •No clinically significant abnormalities in haematology, biochemistry, serology (Ag HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) antibodies, HIV (Human Immunodeficiency Virus) antibodies) and urine tests.
排除标准
- •Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment.
- •Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
- •Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
- •Subject having at screening examination a sitting blood pressure more than or equal to 140/90 mm Hg or lower than or equal to 90/50 mmHg.
- •Subject having at screening examination a pulse more than 100 beats per minute or a body temperature more than 37.7 °C. or a respiratory rate outside the normal range of (14-20 breath per minute).
- •History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
- •Clinically significant abnormalities in screening laboratory tests.
- •Any prescription, over-the-counter and herbal medications within 10 days prior to study dosing.
- •Use of an investigational drug within 3 months prior to dosing in this study.
- •Psychiatric history of current or past psychosis, bipolar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
- •Pregnant or breastfeeding women.
- •History of substance abuse, including alcohol.
- •History of substance or drug dependence, or positive urine drug screen at screening visit.
- •History of head injury.
- •History of sensitivity to any drug.
- •Having donated blood in the last month before start of the study.
- •Any reason or opinion of the investigator that would prevent the subject from participation in the study.
- •Inability to follow the instructions or an unwillingness to collaborate during the study.
研究组 & 干预措施
ApTOLL single dose
ApTOLL is administered intravenously in a single ascending dose pattern in seven dose levels (0.7mg - 70mg). Levels 1 - 3 include one subject per level and levels 4 - 7 include six subjects per level (1 sentinel + 5 subjects).
干预措施: ApTOLL (Drug)
Placebo single dose
Placebo is administered intravenously during seven dose levels. Levels 1 - 3 include one subject per level and levels 4 - 7 include two subjects per level (1 sentinel + 1 subject).
干预措施: Placebo (Other)
ApTOLL multiple dose
ApTOLL is administered intravenously every eight hours during 24h (21mg). This arm includes six subjects (1 sentinel + 5 subjects).
干预措施: ApTOLL (Drug)
Placebo multiple dose
Placebo is administered intravenously every eight hours during 24h. This arm includes twosubjects (1 sentinel + 1 subject).
干预措施: Placebo (Other)
结局指标
主要结局
Incidence of Adverse Events as assessed by CTCAE v4.0
时间窗: From dosing to follow-up (day 15 after dosing)
Adverse Events that occur during the study
Area under the plasma concentration
时间窗: Predose and at different times up to 72 hours post-dose
Area under the plasma concentration versus time curve (AUC)
Peak Plasma Concentration
时间窗: Predose and at different times up to 72 hours post-dose
Peak Plasma Concentration (Cmax)
次要结局
- Laboratory determinations(From screening to follow-up (day 15 after dosing))
- Vital signs(From screening to follow-up (day 15 after dosing))