Open-label Prospective Noncomparative Study of Safety, Tolerability and Pharmacokinetics of PBTZ169 After Single and Multiple Fasting Oral Administration in Increasing Doses in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 主要终点
- Incidence of Drug-related Adverse Events [Safety and Tolerability]
研究概览
简要总结
Open-label prospective non-comparative safety, tolerability and pharmacokinetics ascending dose randomized cohort study of PBTZ169 (capsules 40 mg) in fasted healthy volunteers after single and multiple oral administration
详细描述
Open-label prospective non-comparative safety, tolerability and pharmacokinetics ascending dose randomized cohort study of PBTZ169 (capsules 40 mg) in adult man healthy volunteers after single and multiple oral fasting administration. Study was conducted in one study center in Russian Federation. The study included two stages:
- Stage 1 - single oral fasting administration with dose escalation in 5 cohorts 6 healthy man volunteers each in main groups (plus 1 back-up volunteer in every group);
- Stage 2 - multiple oral fasting administration with dose escalation in 2 cohorts 6 healthy man volunteers each in main groups (plus 1 back-up volunteer in every group).
Screening procedures for each cohort performed within 7 days before the drug prescription and after the end of administration period in previous cohort. Screening in cohorts 2 and 6 was started only after safety tolerability and PK data analysis of previous cohorts.
All volunteers met the study inclusion/exclusion criteria was included successively into the following cohorts on Stage 1 (actual data):
- Cohort 1 (C1) - 6 volunteers of the main group each of whom received once single dose of the drug - 1 capsule containing 40 mg of PBTZ169;
- Cohort 2 (C2) - 6 volunteers of the main group each of whom received once 80 mg of PBTZ169 (2 capsules 40 mg);
- Cohort 3 (C3) - 6 volunteers of the main group each of whom received once 160 mg of PBTZ169 (4 capsules 40 mg);
- Cohort 4 (C4) - 6 volunteers of the main group each of whom received once 320 mg of PBTZ169 (8 capsules 40 mg);
- Cohort 5 (C5) - 6 volunteers of the main group each of whom received once 640 mg of PBTZ169 (16 capsules 40 mg).
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
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Written informed consent received from a volunteer.
- •Man aged 18 to 45 years old, inclusive.
- •Body mass index of 18.5-25 kg/m
- •Verified diagnosis: "healthy" according to data of standard clinical, laboratory and instrumental examination methods performed at screening:
- •Absence of deviations of physical examination parameters and vital signs (systolic blood pressure - 100-129 mm Hg, inclusive; diastolic blood pressure - 70-89 mm Hg, inclusive; heart rate - 60-80 bpm, inclusive);
- •Absence of deviations of laboratory parameters (complete blood count, blood biochemistry, urinalysis and tests for HIV, HBV, HCV, syphilis);
- •Normal parameters of 12-lead ECG;
- •Normal results of photofluorographic or X-ray examination (the results received maximum 6 months before screening can be used).
- •Ability, according to investigators opinion, to comply with all requirements of the protocol.
- •Agreement to use double contraception method during the study participation and for 3 months after the test drug administration - combination of male condom with not less than one of the following methods:
- •female partner using hormonal contraception;
- •using aerosols, creams, suppositories and other agents containing spermicides;
- •female partner using intrauterine device
排除标准
- •Aggravated allergic history, including presence of at least one episode of drug allergy.
- •Chronic diseases of cardiovascular, bronchopulmonary, neuroendocrine systems, ENT and gastrointestinal, hepatic, renal, blood and cutaneous diseases.
- •Chronic diseases of eyes except for mild to moderate myopia, hypermetropia and astigmatism.
- •Gastrointestinal surgeries (except for appendectomy performed not less than 1 year before screening).
- •Acute infections within less than 4 weeks before screening.
- •Regular drug administration within less than 4 weeks before screening.
- •Regular administration or application (including topical) of hormonal drugs for more than 1 week within less than 45 days before the screening.
- •Administration of drugs exerting evident effects on hemodynamics, hepatic function, etc. (barbiturates, omeprazole, cimetidine, etc.) within less than 45 days before the screening.
- •Positive tests for narcotic and psychotropic agents.
- •Donation (450 mL of blood or plasma) within less than 3 months before the screening.
- •Intake of more than 10 U of alcohol per week (1 unit of alcohol is equivalent to 500 mL of beer, 200 mL of vine or 50 mL of strong alcoholic drink) or historical data on alcoholism, narcomania, drug abuse.
- •Mental illnesses.
- •Smoking within half a year before the screening.
- •Previous participation in this clinical study and withdrawal from it due to any reason.
- •Participation in other clinical studies of drugs within less than 6 months before the screening.
- •Planned conception or sperm donation during the study after the test drug administration or during 3 months after the date of drug administration.
研究组 & 干预措施
Cohort 1
6 male healthy volunteers each of whom received once single oral dose of PBTZ169 - 40 mg (1 capsule)
干预措施: PBTZ169 - 40 mg (Drug)
Cohort 2
6 male healthy volunteers each of whom received once single oral dose of PBTZ169 - 80 mg (2 capsules)
干预措施: PBTZ169 - 80 mg (Drug)
Cohort 3
6 male healthy volunteers each of whom received once single oral dose of PBTZ169 - 160 mg (4 capsules)
干预措施: PBTZ169 - 160 mg (Drug)
Cohort 4
6 male healthy volunteers each of whom received once single oral dose of PBTZ169 - 320 mg (8 capsules)
干预措施: PBTZ169 - 320 mg (Drug)
Cohort 5
6 male healthy volunteers each of whom received once single oral dose of PBTZ169 - 640 mg (16 capsules)
干预措施: PBTZ169 - 640 mg (Drug)
Cohort 6
5 male healthy volunteers each of whom received once daily for 14 days 320 mg of PBTZ169 (8 capsules 40 mg)
干预措施: PBTZ169 - 320 mg (multiple administration) (Drug)
Cohort 7
5 male healthy volunteers each of whom received once daily for 14 days 640 mg of PBTZ169 (16 capsules 40 mg)
干预措施: PBTZ169 - 640 mg (multiple administration) (Drug)
结局指标
主要结局
Incidence of Drug-related Adverse Events [Safety and Tolerability]
时间窗: 14±1 days after the drug administration (up to last visit time point)
The frequency of adverse events for which a relationship to the test drug PBTZ169 was noted
次要结局
- Area Under the Plasma Concentration Versus Time Curve in Steady State (AUCss) of PBTZ169(Up to 72 hours after the last drug administration)
- Volume of Steady State Distribution (Vd,ss) of PBTZ169(Up to 72 hours after the last drug administration)
- Area Under the Concentration-time Curve (AUC0-t)(Up to 72 hours after the last drug administration)
- AUC0-t/AUC0-∞(Up to 72 hours after the last drug administration)
- Area Under the Concentration-time Curve (AUC0-∞)(Up to 72 hours after the last drug administration)
- Plasma Half-life Time (T1/2) of PBTZ169(Up to 72 hours after the last drug administration)
- Mean Plasma Retention Time (MRT) of PBTZ169(Up to 72 hours after the last drug administration)
- Total (Plasma) Clearance (Cl) of PBTZ169(Up to 72 hours after the last drug administration)
- Volume of Distribution (Vd) of PBTZ169(Up to 72 hours after the last drug administration)
- Elimination Constant (Kel) of PBTZ169(Up to 72 hours after the last drug administration)
- Peak Plasma Concentration (Сmax) of PBTZ169(Up to 72 hours after the last drug administration)
- Time to Reach Maximum Concentration (Tmax) of PBTZ169(Up to 72 hours after the last drug administration)
- Renal Clearance (Clren) of PBTZ169(Up to 24 hours after the drug administration)
- Peak Steady State Plasma Concentration (Cmax,ss) of PBTZ169(Up to 72 hours after the last drug administration)
- Time to Reach Maximum Steady State Concentration (Tmax,ss) of PBTZ169(Up to 72 hours after the last drug administration)