An Open-label, Prospective Study of Safety, Tolerability, Pharmacokinetics and Food Effects of PBTZ169, 80 mg Capsules, When Used in Ascending Doses in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Number of Adverse Events
研究概览
简要总结
Open-label prospective non-comparative ascending dose randomized cohort study of single and multiple oral administration of PBTZ169 (capsules 80 mg) in healthy volunteers
详细描述
Open-label prospective non-comparativerandomized cohort study of safety, tolerability, pharmacokinetics and the effect of food of PBTZ169 in adult healthy volunteers after single and multiple oral administration. Study was conducted in one study center in the Russian Federation. The study included two stages:
Stage 1 - single or double oral administration with dose escalation (fasted/after meal) in 5 cohorts 10 healthy volunteers each plus 5 back-up volunteers;
Stage 2 - multiple oral administration once a day after meal for 14 days in 1 cohort of 10 healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- All
- 接受健康志愿者
- 是
入选标准
- •Written informed consent from the volunteer.
- •Men and women aged 18-45 years, inclusive.
- •Body mass index of 18.5-30 kg/m
- •Verified "healthy" diagnosis based on physical examination, vital signs, standard laboratory tests (complete blood count and biochemical blood test, urine analysis) and instrumental tests (ECG, fluorography examination or X-ray examination).
- •Negative results of tests for human immunodeficiency virus (HIV), syphilis, hepatitis B (Hbs Ag) and hepatitis C (antibodies to HCV).
- •Ability to comply with all the requirements of the protocol in the opinion of the investigator.
- •Consent of the participant and his/her partner to use reliable contraceptive methods during the study and within 90 days after the end of their participation. A reliable method of contraception is a combination of a male condom with at least one of the following methods:
- •hormonal contraceptives used by the male's partner (only if she does not participate in this clinical study);
- •use of aerosols, creams, suppositories and other agents containing spermicides;
- •use of intrauterine device by female partner.
排除标准
- •History of allergies, including at least one episode of allergy to medications.
- •Chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, ENT, as well as diseases of the gastrointestinal tract, liver, kidneys, blood, skin.
- •Hypolactasia (lactose intolerance, lactase deficiency) or glucose-galatose malabsorption in medical history.
- •Chronic eye diseases except for myopia, hypermetropia and astigmatism of mild and moderate severity.
- •Surgeries on the gastrointestinal tract (except for appendectomy done more than 1 year before screening).
- •Regular administration or use (including externally) of hormonal agent for more than 1 week less than 45 days before screening
- •Regular administration of medicinal products less than 4 weeks before screening.
- •Use of medicinal products that have a pronounced effect on liver function or hemodynamics (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before screening.
- •Positive test for narcotics and psychotropic products.
- •Blood pressure after resting in supine position for at least 5 minutes above 130 mm Hg (systolic blood pressure) and 90 mm Hg (diastolic blood pressure) or below 110 mm Hg (systolic blood pressure) and 60 mm Hg (diastolic blood pressure).
- •Heart rate (according to ECG) after resting in supine position for at least 5 minutes above 90 bpm or below 60 bpm.
- •Blood donation (450 mL of blood or plasma and more) less than 3 months before the screening.
- •Acute infectious diseases less than 4 weeks before screening.
- •Administration of more than 10 units of alcohol per week (1 unit of alcohol is equivalent to 500 mL of beer, 200 mL of wine or 50 mL of a spirit) or history of alcoholism, drug abuse, substance abuse.
- •Mental diseases.
- •Smoking for three months before screening.
- •Participation in any clinical study less than 3 months before screening.
- •Planned conception or sperm donation during the study after the administration of the investigational product or within 3 months after the last administration of the product.
- •Positive pregnancy test for women.
- •Breastfeeding period.
研究组 & 干预措施
Cohort 1 (C1A), PBTZ169
Two doses of PBTZ169: 640 mg OD fasted and 640 mg OD after meal. Wash-out period ≥6 days.
干预措施: PBTZ169 640 mg OD (Drug)
Cohort 1 (C1B), PBTZ169
Two doses of PBTZ169: 640 mg OD after meal and 640 OD mg fasted. Wash-out period ≥6 days.
干预措施: PBTZ169 640 mg OD (Drug)
Cohort 2 (C2), PBTZ169
Single dose of PBTZ169: 960 mg fasted
干预措施: PBTZ169 960 mg SD (Drug)
Cohort 3 (C3), PBTZ169
Two doses of PBTZ169: 640 mg twice a day (fasted) with a 12-hour interval; total daily dose - 1280 mg
干预措施: PBTZ169 640 mg BiD (Drug)
Cohort 4 (C4), PBTZ169
Single dose of PBTZ169: 1280 mg fasted
干预措施: PBTZ169 1280 mg SD (Drug)
Cohort 5 (C5), PBTZ169
Multiple administration of PBTZ169: 1280 mg once a day after meal for 14 days
干预措施: PBTZ169 1280 mg MD (Drug)
结局指标
主要结局
Number of Adverse Events
时间窗: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Safety and tolerability: number of (S)AEs
Number of Subjects With AEs
时间窗: Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake
Safety and tolerability: number of subjects with adverse events
次要结局
- Trough Concentration With Repeated Administration (Ctrough)(Up to 72 hours after the last drug administration)
- Results of Physical Examination: CS Deviations(Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake)
- Peak Plasma Concentration (Сmax)(In the dosing interval (up to 72 hours after the last drug administration))
- CS Changes in Vital Signs(Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake)
- Plasma Half-life Time (T1/2)(Up to 72 hours after the last drug administration)
- ECG Results (Safety and Tolerability)(Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake)
- Laboratory Examinations Results (Safety and Tolerability)(Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake)
- Time to Reach Maximum Concentration (Tmax)(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)
- Area Under the Concentration-time Curve (AUC0-∞)(Up to 72 hours after the last drug administration)
- Area Under the Concentration-time Curve (AUC0-24)(In the dosing interval (up to 24 hours after drug administration))
- Total Clearance (Clt/F)(Up to 72 hours after the last drug administration)
- Volume of Distribution (Vd/F)(Up to 72 hours after the last drug administration)
- Elimination Constant Kel(Up to 72 hours after the last drug administration)
- Relative Bioavailability(Up to 72 hours after the last drug administration)
- Relative Degree of Absorption(Up to 72 hours after the last drug administration)
- Number of Subjects With CS Changes in Vital Signs(Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake)