NCT03334734终止2 期
Multicenter, Open, Randomized Study With Active Control to Evaluate the Early Bactericidal Activity, Safety and Pharmacokinetics of the Drug PBTZ169 When Used in Patients With First-diagnosed Tuberculosis of the Respiratory System With Bacterial Excretion and Saved Bacterial Susceptibility to Isoniazid and Rifampicin
Nearmedic Plus LLC0 个研究点目标入组 16 人开始时间: 2016年12月16日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 16
- 主要终点
- Early Bactericidal Activity (0-14)
研究概览
简要总结
Multicenter, open, randomized study with active control (isoniazid) to evaluate the early antibacterial activity, safety and pharmacokinetics of the drug PBTZ169 (capsules 80 mg) when used in patients with first-diagnosed tuberculosis of the respiratory system with bacterial excretion and saved bacterial susceptibility to isoniazid and rifampicin
详细描述
This phase 2a study is aimed to evaluate the early bactericidal activity of a new anti-tuberculosis drug PBTZ169 (capsules 80 mg), and its results will allow preliminary evaluate antimycobacterial properties of PBTZ169 and confirm a potentially more effective dose for subsequent studies. This study is an open, randomized comparative efficacy (on the parameter of early bactericidal activity), safety and pharmacokinetics study of PBTZ169 in patients with first-diagnosed lung tuberculosis and preserved sensitivity to base antimycobacterial drugs: rifampicin and isoniazid.
Within the framework of the study, it is planned to use the studied drugs (PBTZ169 and isoniazid) as monotherapy within 14 days. Isoniazid is used as a "positive control", that is, in order to determine whether the method of assessing efficacy on the parameter of early bactericidal activity is working.
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent received from a volunteer
- •Men and women aged 18 to 65 years, inclusive
- •The first-diagnosed active pulmonary tuberculosis, confirmed by characteristic radiographic changes (infiltration, dissemination, destruction) during radiography or computed tomography of chest organs, without damage to other organs or with the defeat of one or more of the following organs: larynx, trachea, bronchi, lymph nodes
- •The amount of sputum given by the patient is sufficient for carrying out the analyzes provided for by the protocol, but not less than 4-5 ml at the screening
- •The presence of acid-fast mycobacteria in the sputum according to the results of microscopy of smears (1+ and more using the method of microscopy with luminescent dye staining according to the Order of the Ministry of Health of the Russian Federation of March 21, 2003 No. 109, the last edition) and the detection of the DNA of mycobacteria of tuberculosis by the results of molecular genetic methods of diagnosis
- •Body weight not less than 51 kg
- •Body mass index of 18.5-25 kg/m2
- •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
- •Extrapulmonary localization of tuberculosis
- •Presence of resistance to rifampicin and / or isoniazid in the study of sputum samples using molecular genetic methods
- •Admission of any anti-tuberculosis drugs from the moment of diagnosis of tuberculosis to the moment of inclusion in the study
- •The presence of absolute indications for surgical treatment of tuberculosis at the time of screening
- •Positive tests for serological markers of syphilis or HIV infection during screening; active hepatitis or decompensated hepatic cirrhosis
- •Aggravated allergic history, including presence of at least one episode of drug allergy
- •The values of renal and / or hepatic parameters according to laboratory analyzes (taking into account the range of normal laboratory values):
- •Aspartate aminotransferase (AST) level > 2.0 x upper limit of the norm
- •Alanine aminotransferase (ALT) level > 2.0 x upper limit of norm
- •General bilirubin level > 1.5 x upper limit of norm
- •Creatinine level > 1.5 x upper limit of norm
- •Individual drug components intolerance
- •Presence in the anamnesis of malignant neoplasms, except for basal cell skin cancer
- •The presence of severe chronic somatic diseases in the stage of decompensation, including diseases of the cardiovascular, bronchopulmonary, neuroendocrine system, ear, nose and throat (ENT) organs, the gastrointestinal tract, liver, kidneys, blood, skin, or any other somatic or mental diseases that, according to the researcher, prevent the patient from entering the study
- •Gastrointestinal surgeries (except for appendectomy performed not less than 1 year before screening)
- •Mental illness that may interfere with the patient's compliance with the protocol
- •Diabetes mellitus
- •Acute viral and bacterial infections at the time of enrollment or within 2 weeks before enrollment
- •Alcoholism (except in cases when the patient is able, in the opinion of the researcher, to refrain from taking alcohol during the period of participation in the study), drug addiction, abuse of medicines
- •Positive tests for narcotic and psychotropic agents
- •Regular admission or use (including externally) of any hormonal medicines lasting more than 1 week less than 30 days before screening (with the exception of oral hormonal contraceptives and intrauterine spirals containing hormones)
- •Use of cytostatic drugs less than 30 days before screening
- •Multiple admission of drugs with the described in the instructions for medical use adverse events related to nervous system, hemodynamic and hepatic functions with frequencies "very frequent" (≥10%) and "often" (≥1% and <10%) less than 21 days before screening
- •Pregnancy or lactation period
- •Planned conception or sperm donation during the study after the test drug administration or during 3 months after the last date of drug administration
- •Participation in other clinical studies of drugs within less than 3 months before the screening
研究组 & 干预措施
PBTZ169, 160 mg
Experimental
2 capsules 80 mg of PBTZ169 once a day for 14 days
干预措施: PBTZ169 (Drug)
PBTZ169, 320 mg
Experimental
4 capsules 80 mg of PBTZ169 once a day for 14 days
干预措施: PBTZ169 (Drug)
PBTZ169, 640 mg
Experimental
8 capsules 80 mg of PBTZ169 once a day for 14 days
干预措施: PBTZ169 (Drug)
Isoniazid, 600 mg
Active Comparator
2 tablets 300 mg of Isoniazid once a day for 14 days
干预措施: Isoniazid (Drug)
结局指标
主要结局
Early Bactericidal Activity (0-14)
时间窗: 14 days after the onset of monotherapy
Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): PCR, the mean of two measurements at the Visit
次要结局
- Residual Concentration (Ctrough) of PBTZ169(Up to 72 hours after the last drug administration)
- Average Concentration (Css,av) of PBTZ169(Up to 72 hours after the last drug administration)
- Minimal Plasma Concentration (Сmin) of PBTZ169(Up to 72 hours after the last drug administration)
- AUC(0-24)(Up to 24 hours after the last drug administration)
- AUC (0-t)(Up to 72 hours after the last drug administration)
- Accumulation Ratios for the PK Parameters AUC(0 -24)(24 hours after the first and the last drug administration)
- Volume of Distribution (Vd) of PBTZ169(Up to 72 hours after the last drug administration)
- Plasma Half-life Time (T1/2) of PBTZ169(24 hours after the last drug administration)
- Early Bactericidal Activity (0-2)(2 days after the onset of monotherapy)
- Early Bactericidal Activity (0-7)(7 days after the onset of monotherapy)
- Peak Plasma Concentration (Сmax) of PBTZ169(for single dosing , Day 1 (24 h after 1st dose of PBTZ169))
- Time to Reach Maximum Concentration (Tmax) of PBTZ169(Up to 72 hours after the last drug administration)
- AUC(0-∞) of PBTZ169(Up to 72 hours after the last drug administration)
- Fluctuations (%) in the Dosing Interval(Up to 72 hours after the last drug administration)
- Elimination Constant (Kel) of PBTZ169(72 hours after the last drug administration)
- Total (Plasma) Clearance (Clt) of PBTZ169(24 hours after the last drug administration)
研究者
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