An Open-label Study of Pharmacokinetics, Safety and Tolerability of Drug DD217, Enteric-coated Tablets, 10 mg, Developed by PharmaDiall Ltd (Moscow), on Healthy Volunteers Receiving Single Dose in Fasting State (Phase I)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Total Adverse Events (AE)
研究概览
简要总结
In the course of the clinical study, the pharmacokinetics, pharmacodynamics, safety and tolerability of Dimolegin (DD217) 10 mg enteric-coated tablets after single administration to healthy volunteers at increasing doses were studied.
24 volunteers participated in the study. The randomization procedure was carried out for 24 volunteers selected at screening. In Group 1 6 volunteers were randomized , in Group 2 6 volunteers were randomized, and in Group 3 12 volunteers were enrolled. Group 1 volunteers took the study drug at a dose of 20 mg once, group 2 volunteers took the study drug at a dose of 40 mg once, and group 3 volunteers took the study drug at a dose of 60 mg once.
详细描述
Study objectives were:
- to evaluate the safety of different single doses of Dimolegin (DD217) in healthy volunteers;
- to evaluate the tolerance of different single doses of Dimolegin (DD217) in healthy volunteers;
- to evaluate pharmacokinetic parameters with a single dose of Dimolegin (DD217) in increasing doses;
- to evaluate the effect of Dimolegin (DD217) on coagulation profile parameters (prothrombin time, activated partial thromboplastin time (aPTT), anti-Xa activity) with a single dose in healthy volunteers (pharmacodynamic study).
Study design was an open study of the pharmacokinetics, safety and tolerability of Dimolegin (DD217) after single administration to healthy volunteers in fasting conditions (phase 1).
Study population was: screened - 40, randomized - 24, per protocol population - 24.
The study was open, prospective, non-randomized with sequential enrollment of volunteers with dose escalation Group No. 1 (n=6) consisted of 2 cohorts with 3 volunteers per each. Volunteers of Cohorts 1 and 2 received Dimolegin (DD217) once at a dose of 20 mg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •18-45 years
- •Verified "healthy" diagnosis based on the findings of routine clinical, laboratory, and instrumental examinations
- •Body mass index (BMI) is 18.5-30.0 kg/m2
- •Consent to the use of barrier contraception methods during the study period and for 3 months after it
- •Written consent of the volunteer to enrollment
排除标准
- •Aggravated allergy history
- •Drug intolerance
- •Acute and chronic cardiovascular, bronchopulmonary, neuroendocrine diseases as well as gastrointestinal, hepatic, renal, hematological diseases
- •Systolic blood pressure less than 90 mmHg or above 130 mmHg
- •Diastolic blood pressure less than 70 mmHg or above 89 mmHg
- •Pulse rate less than 60 bpm or more than 89 bpm
- •Gastrointestinal surgery (except for appendectomy)
- •Acute infectious diseases less than 4 weeks prior to the study
- •Any abnormalities detected during screening from the clinical laboratory center reference values (including estimated glomerular filtration rate (GFR), coagulation profile), clinical and instrumental study methods
- •Hypersensitivity to the study product components
- •Taking prescription or over-the-counter medications, including dietary supplements, herbal products, vitamins, homeopathic medicines, less than 2 weeks before the start of the study
- •Administration of medicinal products with expressed effect on hemodynamics, hepatic function and other systems (e.g. barbiturates, omeprazole, cimetidine, etc.) less than 2 months prior to the study initiation
- •Blood donation (≥ 450 mL of blood or plasma) less than 2 months prior to the study
- •Participation in clinical studies of drug products less than 3 weeks prior to the study initiation
- •Intake of more than 10 units of alcohol per week (10 mL of pure (100 %) ethanol is taken for 1 unit of alcohol, this is the amount that the body of a healthy adult breaks down within an hour; 1 unit of alcohol is equivalent to 0.33 liters of beer, 150 mL of wine or 30 mL of hard liquors), or history of alcohol or drug dependence, drug abuse
- •Smoking > 10 cigarettes per day
- •Positive urine drug test (cocaine, cannabis, amphetamines, barbiturates and opioids)
- •Positive alcohol breath test
- •Lost for follow-up during 29 days, inability to comply with the schedule of visits, inability to be hospitalized for 2.5 days
- •Inability to understand or follow protocol instructions
研究组 & 干预措施
Group No. 1 (n=6) Dimolegin - 20 mg
Group No. 1 (n=6) consisted of 2 cohorts with 3 volunteers per each. Volunteers of Cohorts 1 and 2 received Dimolegin (DD217) once at a dose of 20 mg
干预措施: Dimolegin (Drug)
Group No. 2 (n=6) Dimolegin - 40 mg
Group No. 2 (n=6) consisted of 2 cohorts with 3 volunteers per each. Volunteers of Cohorts 3 and 4 received Dimolegin (DD217) once at a dose of 40 mg
干预措施: Dimolegin (Drug)
Group No. 3 (n=12) Dimolegin - 60 mg
Group No. 3 (n=12) consisted of 3 cohorts. Cohorts 5 and 6 included 3 volunteers per each, and Cohort 7 included 6 volunteers. All Group 3 volunteers received Dimolegin (DD217) once at a dose of 60 mg
干预措施: Dimolegin (Drug)
结局指标
主要结局
Total Adverse Events (AE)
时间窗: 28 Days
Number of of subjects experiencing AEs, serious adverse events (SAEs), or discontinuations due to AEs
次要结局
- Steady-state Area Under the Plasma Concentration Versus Time Curve From Time Zero to 12 Hours of Dioxaban (AUC (0-12))(7 Days)
- Steady-state Maximum Observed Plasma Concentration of Dioxaban (Cmax)(7 Days)
- The increase in Anti-Xa activity(2 Days)
- The increase in International Normalised Ratio (INR)(2 Days)
- The increase in Activated Partial Thromboplastin Time (aPTT)(2 Days)
- Steady state Plasma Clearance of Dioxaban (CL)(7 Days)
- Steady state Elimination of Half-Life of Dioxaban (t½)(7 Days)
- Steady-state Time to Maximum Observed Plasma Concentration of Dioxaban(7 Days)