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临床试验/NCT04174937
NCT04174937已完成1 期

A Randomized, Placebo-controlled Study of the Tolerability, Safety and Pharmacokinetics of PA in Healthy Volunteers

Scientific Center for Anti-infectious Drugs, Kazakhstan1 个研究点 分布在 1 个国家目标入组 72 人开始时间: 2016年6月17日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
发起方
入组人数
72
试验地点
1
主要终点
Adverse Events (AE)
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a first-in-human (FIH) study to explore the safety, tolerability and pharmacokinetics of PA after oral ascending dose administration to healthy male volunteers.

详细描述

The first-in-human dose (FHD) trial is a randomized, double-blind, placebo-controlled, dose-escalation trial assessing safety, tolerability and pharmacokinetics (PK) of single and multiple oral doses of PA in healthy male subjects.

The study consists of two stages: single dose administration and multiple dose administration.

The single dose administration stage includes 5 cohorts, multiple dose administration stage includes at least 4 cohorts (groups). Each cohort includes 8 subjects (6 active drugs and 2 placebos). Cohorts intake ascending doses of study drug. The dose of 1st cohort is 1,0 mg/ml, the doses for the following cohorts will be estimated by the Data Monitoring Committee based on pharmacokinetics and safety results of previous group.

For each subject study includes screening period, one baseline period on Day -1, a treatment period (1 day - at single dose stage; 14 days - at multiple dose stage), followed by safety, PK, assessments up to 72-96 hours post dose. Follow-up visits will take place on Day 7 ; 30; 60 (single dose stage) and 30; 60; 90 (multiple dose stage).

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Other
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

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

  • •Age 18 to 55 years
  • •Body mass index 16 to 30
  • •Subjects should be in good physical and mental health based on medical history, clinical examination and laboratory investigations
  • •Subjects should have signed informed consent prior to screening and the clinical study after they have read and understood the objective, conduct, risks related to the study, and their rights as study participants
  • •Subjects should have signed informed consent for being tested for HIV
  • •Subjects should have signed informed consent to be tested for alcoholemia, use of cannabinoids, cocaine, morphine, benzodiazepines, barbiturates and amphetamine

排除标准

  • •Subjects should not have evidence of any physical and/or mental health issues at screening and/or results of any clinical, laboratory and/or technical procedures at screening outside of the normal range
  • •Subjects should not be taking any concomitant medication
  • •Subjects should not have a history of allergies, hypersensitivity or intolerance to iodine or iodide or to medicines containing iodine such as contrast media used for radiologic examinations
  • •Subjects should not have a history of addiction or abuse of drugs or alcohol
  • •Subjects should not be in a position of subordination or other dependence on persons involved in the study such as sponsor, investigators, or any other person or institution interested in its results
  • •Subjects should not be members of the armed forces or prison inmates
  • •Subjects should not have positive serology for Hepatitis B, Hepatitis C or HIV
  • •Subjects should not have any apparent functional and/or physical defects which may or interfere with the study or distort results

研究组 & 干预措施

Potentiator of antibiotics (PA)

Experimental

Potenciator of antibiotics (PA) , albumin complex of tetraiodid was given per os, single and multiple doses for the different periods (but not exceeding 14 days)

干预措施: Potentiator of antibiotics (PA) (Drug)

Patients taking placebo PA

Placebo Comparator

Placebo without any active pharmaceutical ingredients was given per os dosed for the patients in same periods of time as per experimental group, single and multiple doses for the different periods (but not exceeding 14 days)

干预措施: Placebo PA (Other)

结局指标

主要结局

Adverse Events (AE)

时间窗: Adverse event reporting will be performed throughout the trial from the Screening visit until the Final visit (up to 90 days)

The safety of ascending single and multiple doses of Study Drug in healthy male subjects will be assessed by adverse event and serious adverse event monitoring.

次要结局

  • Half-life time (T1/2)(Blood collections at the following time points: 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration)
  • Total clearance (СL)(Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration)
  • Mean residence time of drug (MRT)(Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration)
  • Area under plasma concentration time curve (AUC∞)(Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration)
  • Maximum concentration of drug in the blood (Cmax)(Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration)
  • Time to reach maximum drug concentration (Tmax)(Blood collections at the following time points: before drug intake (two points - 1 day and 10 min), and 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration)
  • Volume of distribution (Vλz)(Blood collections at the following time points: 5 min, 15 min, 30 min, and 1, 1.5; 2; 3; 6; 9; 12; 15; 24; 48 and 72 hours after study drug administration)
  • Drug elimination rate constant (Lambda-z (λz))(0-72 hours)
  • Drug excretion (%)(Urine samples taken during 0-96 h after drug intake)
  • Change in free triiodothyronine (FT3)(Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90)
  • Change in total thyroxine (TT4)(Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90)
  • Change in free thyroxine (FT4)(Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90)
  • Change in anti-thyroglobulin antibody(Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90)
  • Change in anti-thyroid peroxidase antibody(Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90)
  • Accumulation index (Rac)(Blood sampling at multiple dosing: Day 1-17)
  • Change in thyroid stimulating hormone (TSH)(Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90)
  • Change in total triiodothyronine (TT3)(Screening visit; Single dose intake: Day 1 - before and 12 hours after dose; Day 2; Day 3; Day 60. Multiple dose intake: Day 1 - before and 12 hours after dosing; Days 2;3;5;9;14;17;30;60;90)
  • Change from baseline in thyroid ultrasound(Screening visit; Final visit (Day 60 - at Single dose intake; Day 90 - at Multiple dose intake))
  • Change from baseline in electrocardiogram (ECG)(Screening visit; before dose (Day -1); Day 1 - after dose (4 hours); Final visit (Day 60). Multiple dose intake: before dose (Day -1); Day 1 and 15 - 4 hours after dose; Final visit (Day 90).)
  • Change in Respiratory Rate(every visit up to 90 days)
  • Change in Heart Rate(every visit up to 90 days)
  • Change in Blood Pressure(every visit up to 90 days)
  • Change in Body Temperature(every visit up to 90 days)
  • Symptoms of musculoskeletal system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of cardiovascular system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of lymphatic system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of nervous system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of Respiratory system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of Gastrointestinal system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of urinary system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of Endocrine system(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Symptoms of Skin and subcutaneous tissue(From baseline till the last visit (daily during hospital stay, every visit in follow-up period - up to 90 days))
  • Change in Alanine transaminase (ALT)(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Aspartate aminotransferase (AST)(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Bilirubin / bilirubin fractions(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Creatinine(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Alkaline phosphatase(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Blood Urea Nitrogen(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Uric acid(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Alpha-amylase (α-amylase)(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Serum total protein(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Albumin level in blood(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Glucose level in blood(Single dose study:Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose study: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Total cholesterol(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Potassium in blood(Single dose study:Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose study: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in activated partial thromboplastin time (aPTT)(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90)
  • Change in Serum calcium(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in leucocytes number in the blood(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in thrombocytes number in the blood(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Serum magnesium(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in hematocrit(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in Erythrocyte Sedimentation Rate (ESR))(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in erythrocytes number in blood(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in prothrombin index(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90)
  • Change in Urinary glucose(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Hematuria(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Leucocyturia(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in hemoglobin(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in prothrombin ratio(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90)
  • Change in thrombin time(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 15;16;17;30;60;90)
  • Change of protein level in urine(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Ketonuria(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in urine pH(Single dose intake: Screening visit; before dose (Day -1); Day 1 - after dose (3 hours); Days 2;7;30;60. Multiple dose intake: Screening visit; before dose (Day -1); Days 1; 3;10;14-after dose (3 hours); Days 17;30;60;90)
  • Change in immunoglobulin A (IgA) level in blood(Single dose study: before dose (Day -1); Day 1 - after dose (3 hours); Day 2. Multiple dose study: before dose (Day -1) Days 14; 17; 30;60; 90)
  • Change in immunoglobulin M (IgM) level in blood(Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Day 2. Multiple dose intake: before dose (Day -1) Days 14; 17; 30;60; 90)
  • Change in immunoglobulin G (IgG) level in blood(Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Day 2. Multiple dose intake: before dose (Day -1) Days 14; 17; 30;60; 90)
  • Change in immunoglobulin E (IgE) level in blood(Single dose intake: Screening visit; Day 1 - after dose (3 hours); Day 2. Multiple dose intake: Screening visit; Days 14; 17; 30;60; 90)
  • Change in Rheumatoid factor(Single dose intake: Screening visit; Day 1 - after dose (3 hours); Day 2. Multiple dose intake: Screening visit; Days 14; 17; 30;60; 90)
  • Change in C-Reactive Protein(Single dose intake: Screening visit; Day 1 - after dose (3 hours); Day 2. Multiple dose intake: Screening visit; Days 14; 17; 30;60; 90)
  • Change in Antimitochondrial Antibody(Single dose intake: before dose (Day -1); Day 30; Day 60. Multiple dose intake: before dose (Day -1); Day 60; Day90)
  • Change in antinuclear antibody(Single dose intake: before dose (Day -1); Day 30; Day 60. Multiple dose intake: before dose (Day -1); Day 60; Day90)
  • Change from baseline in CD3+tcells(Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90)
  • Change from baseline in CD4+tcells(Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90)
  • Change from baseline in CD8+tcells(Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90)
  • Change from baseline in Ratio CD4/CD8(Single dose intake: before dose (Day -1); Day 1 - after dose (3 hours); Days 2; 17; 30; 60. Multiple dose intake: before dose (Day -1); Day 1; 14 - after dose (3 hours); Days 17;30;60;90)

研究者

发起方
Scientific Center for Anti-infectious Drugs, Kazakhstan
申办方类型
Industry
责任方
Sponsor

研究点 (1)

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