Phase 2a Study of PBTZ169
Condition: Tuberculosis
MeSH terms: Tuberculosis
Intervention: PBTZ169; Isoniazid
Intervention description: Once a day for 14 days; Once a day for 14 days
Intervention MeSH terms: Isoniazid; Macozinone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Tuberculosis; PBTZ169; antimycobacterial

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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