A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Doses of SP-8008 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with serious adverse drug reactions (SADRs)
研究概览
简要总结
This is a single-centre, double-blind, randomised, placebo-controlled single oral-dose escalation study in healthy male subjects. It is planned to enrol approximately 48 subjects into up to 6 planned dose level cohorts.
Subjects will be randomly assigned to receive a single oral dose of active Investigational medicinal product (IMP) or matching placebo in a sequential escalating manner with at least 14 days planned between dose cohorts. Dose review of the preceding dose will take place during the 14 day interval.
The study will consist of escalating single doses in sequential cohorts. Each dose level cohort will consist of 8 subjects; 6 subjects will receive SP-8008 and 2 subjects will receive placebo according to the randomisation schedule. For all dose levels the first 2 sentinel subjects will be randomised 1:1 to placebo or SP-8008, and the remaining 6 subjects will be randomised 1:5 to placebo or SP-8008, respectively.
详细描述
Investigational medicinal product (IMP) will be administered at only 1 dose level at a time. Following each of Periods 1, 2, 3, 4, and 5, there will be a period of interim analysis and review of safety, PK and available PD data from the previous period(s) in order to determine which SP 8008 formulation and dose to administer further regimens. Administration at the next dose level will not begin until the safety and tolerability of the preceding dose level have been evaluated and deemed acceptable by the investigator and sponsor, and the exposure of SP-8008 remains within the pre specified limits following interim review. There will be an interval of no less than 14 days between the dosing of successive cohorts, unless a subject cohort returns to a dose that is lower than that already given in a previous cohort eg to obtain dose linearity information. Dose escalation will be guided by emerging safety, PK and available PD data and confirmed after each interim data review meeting.
There is the option to assess the safety, PK and PD of an alternative formulation. This formulation will be invoked if, following review of data from the preceding periods, it is decided that the exposure from the current formulation may not be ideal for future development.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Healthy males
- •Age 18 to 55 years of age at the time of signing informed consent
- •Body mass index of 18.0 to 32.0 kg/m2 as measured at screening
- •Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination), electrocardiogram (ECG) and laboratory investigations (haematology, coagulation, clinical chemistry and urinalysis) and bleeding time (bleeding time may be measured on Day 1)
- •Must be willing and able to communicate and participate in the whole study
- •Must provide written informed consent
- •Must agree to adhere to the contraception requirements
排除标准
- •Female subjects
- •Subjects who had received any investigator medicinal product (IMP) in a clinical research study within the 3 months or 90 days prior to Day 1
- •Subjects who were study site employees, or immediate family members of a study site or sponsor employee
- •Subjects who had previously been enrolled in this study
- •History of any drug or alcohol abuse in the past 2 years
- •Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type)
- •Current smokers and those who had smoked within the last 12 months. A confirmed breath carbon monoxide (CO) reading of greater than 10 ppm at screening or admission Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months
- •Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months
- •Subjects without suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
- •Clinically significant abnormal biochemistry, haematology, coagulation or urinalysis as judged by the investigator including investigator medicinal product (PT) >14 s, investigator medicinal product (aPTT) > reference laboratory values, platelet count ≤100,000 mm3, alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) >2× upper limit of normal, white blood cells ≤3000 × 109/L, haemoglobin <11 g/dL, total bilirubin >20 µmol/L, bleeding time >15 min
- •Any clinically significant medical disorders increasing the tendency to bleed easily, or a history of recent trauma or surgery, or a history of gout and renal stones
- •Confirmed positive drugs of abuse test result
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
- •Evidence of renal impairment at screening, as indicated by an estimated Creatinine Clearance (CrCl) of <80 mL/min using the Cockcroft-Gault equation
- •History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
- •Serious adverse reaction (SAE) or serious hypersensitivity to any drug or the formulation excipients
- •Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever was allowed unless it was active
- •Donation or loss of greater than 400 mL of blood within the previous 3 months
- •Subjects who were taking, or had taken, any prescribed or over-the-counter drug, herbal remedies or supplements in the 14 days before IMP administration; these included fish oil/Omega-3, St. John's wort, ginseng, garlic, gingko, saw palmetto, echinacea, yohimbine, liquorice and black cohosh. Exceptions may have applied on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the principal investigator (PI) and sponsor's medical monitor.
- •Failure to satisfy the investigator of fitness to participate for any other reason
研究组 & 干预措施
Cohort 1: 200mg SP-8008 Prototype Capsule A
Treat 200 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: SP-8008 Prototype Capsule A (Drug)
Cohort 1: 200mg SP-8008 Prototype Capsule A
Treat 200 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: Placebo (Drug)
Cohort 2: 400mg SP-8008 Prototype Capsule A
Treat 400 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: SP-8008 Prototype Capsule A (Drug)
Cohort 2: 400mg SP-8008 Prototype Capsule A
Treat 400 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: Placebo (Drug)
Cohort 3: 800mg SP-8008 Prototype Capsule A
Treat 800 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: SP-8008 Prototype Capsule A (Drug)
Cohort 3: 800mg SP-8008 Prototype Capsule A
Treat 800 mg SP-8008 Prototype Capsule A or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: Placebo (Drug)
Cohort 4: 800 mg SP-8008 Prototype Capsule B
Treat 800 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: SP-8008 Prototype Capsule B (Drug)
Cohort 4: 800 mg SP-8008 Prototype Capsule B
Treat 800 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: Placebo (Drug)
Cohort 5: 1200 mg SP-8008 Prototype Capsule B
Treat 1200 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: SP-8008 Prototype Capsule B (Drug)
Cohort 5: 1200 mg SP-8008 Prototype Capsule B
Treat 1200 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: Placebo (Drug)
Cohort 6: 1800 mg SP-8008 Prototype Capsule B
Treat 1600 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: SP-8008 Prototype Capsule B (Drug)
Cohort 6: 1800 mg SP-8008 Prototype Capsule B
Treat 1600 mg SP-8008 Capsule B or matching placebo. 6 out of 8 subjects were administrated SP-8008 and the other two were received Placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with serious adverse drug reactions (SADRs)
时间窗: Follows up to 7 days
The number of subject who experienced a serious adverse drug reaction
Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with severe adverse drug reactions (ADRs)
时间窗: Follows up to 7 days
The number of subject who experienced a severe adverse drug reaction
Safety profile of single doses of SP-8008 in healthy male subjects was evaluated with clinically significant non-serious adverse events (AEs)
时间窗: Follows up to 7 days
The number of subject who experienced a clinically significant non serious adverse event
次要结局
- To characterize the pharmacokinetics of SP-8008 in health male subjects. - Peak Plasma Concentration (Cmax)(Follows up to 48 hours)
- To characterize the pharmacokinetics of SP-8008 in health male subjects. - Area under the plasma concentration versus time curve from time zero to infinity (AUC[0-∞])(Follows up to 48 hours)
- To evaluate the effect of single dose SP-8008 on platelet function through Shear stress-induced platelet aggregation (SIPA)(Follows up to 48 hours)
- To evaluate the effect of single dose SP-8008 on platelet function through inhibition of platelet aggregation (IPA)(Follows up to 48 hours)