Safety, Tolerability, Pharmacokinetics and Food Effects Study of PBTZ169
Condition: Healthy Subjects
Intervention: PBTZ169 640 mg OD; PBTZ169 640 mg BiD; PBTZ169 960 mg SD; PBTZ169 1280 mg SD; PBTZ169 1280 mg MD
Intervention description: Two administrations once a day with a wash-out period: food effect; Twice a day fasted; 1 day of administration; Once a day fasted; Once a day fasted; Once a day after meal, 14 doses
Intervention MeSH terms: Macozinone
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: PBTZ169; Macozinone; Antimycobacterial; Tuberculosis; Drug Resistant Tubercolosis; MDR-TB; XDR-TB

Summary:

      Open-label prospective non-comparative ascending dose randomized cohort study of single and
      multiple oral administration of PBTZ169 (capsules 80 mg) in healthy volunteers
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent from the volunteer.

          2. Men and women aged 18-45 years, inclusive.

          3. Body mass index of 18.5-30 kg/m2.

          4. 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).

          5. Negative results of tests for human immunodeficiency virus (HIV), syphilis, hepatitis
             B (Hbs Ag) and hepatitis C (antibodies to HCV).

          6. Ability to comply with all the requirements of the protocol in the opinion of the
             investigator.

          7. 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.

        Exclusion Criteria:

          1. History of allergies, including at least one episode of allergy to medications.

          2. Chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, ENT,
             as well as diseases of the gastrointestinal tract, liver, kidneys, blood, skin.

          3. Hypolactasia (lactose intolerance, lactase deficiency) or glucose-galatose
             malabsorption in medical history.

          4. Chronic eye diseases except for myopia, hypermetropia and astigmatism of mild and
             moderate severity.

          5. Surgeries on the gastrointestinal tract (except for appendectomy done more than 1 year
             before screening).

          6. Regular administration or use (including externally) of hormonal agent for more than 1
             week less than 45 days before screening

          7. Regular administration of medicinal products less than 4 weeks before screening.

          8. Use of medicinal products that have a pronounced effect on liver function or
             hemodynamics (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before
             screening.

          9. Positive test for narcotics and psychotropic products.

         10. 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).

         11. Heart rate (according to ECG) after resting in supine position for at least 5 minutes
             above 90 bpm or below 60 bpm.

         12. Blood donation (450 mL of blood or plasma and more) less than 3 months before the
             screening.

         13. Acute infectious diseases less than 4 weeks before screening.

         14. 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.

         15. Mental diseases.

         16. Smoking for three months before screening.

         17. Participation in any clinical study less than 3 months before screening.

         18. 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.

         19. Positive pregnancy test for women.

         20. Breastfeeding period.