Safety, Tolerability, Pharmacokinetics and Food Effects Study of PBTZ169

NCT04150224 | Completed Phase 1 Results

• 1 other identifier: PBTZ169-Z00-C01-3
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Healthy Subjects

Keywords

PBTZ169; Macozinone; Antimycobacterial; Tuberculosis; Drug Resistant Tubercolosis; MDR-TB; XDR-TB

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events

  Safety and tolerability: number of (S)AEs

  Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake

• Number of Subjects With AEs

  Safety and tolerability: number of subjects with adverse events

  Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake

Secondary Outcomes (17)

• CS Changes in Vital Signs

  Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake

• ECG Results (Safety and Tolerability)

  Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake

• Laboratory Examinations Results (Safety and Tolerability)

  Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake

• Results of Physical Examination: CS Deviations

  Up to last visit time point: C2, C3, C4 up to Day 7; C1 up to Day 13; C5 up to Day 21 after first drug intake

• Peak Plasma Concentration (Сmax)

  In the dosing interval (up to 72 hours after the last drug administration)

Study Arms (6)

Cohort 1 (C1A), PBTZ169

EXPERIMENTAL

Two doses of PBTZ169: 640 mg OD fasted and 640 mg OD after meal. Wash-out period ≥6 days.

Drug: PBTZ169 640 mg OD

Cohort 1 (C1B), PBTZ169

EXPERIMENTAL

Two doses of PBTZ169: 640 mg OD after meal and 640 OD mg fasted. Wash-out period ≥6 days.

Drug: PBTZ169 640 mg OD

Cohort 2 (C2), PBTZ169

EXPERIMENTAL

Single dose of PBTZ169: 960 mg fasted

Drug: PBTZ169 960 mg SD

Cohort 3 (C3), PBTZ169

EXPERIMENTAL

Two doses of PBTZ169: 640 mg twice a day (fasted) with a 12-hour interval; total daily dose - 1280 mg

Drug: PBTZ169 640 mg BiD

Cohort 4 (C4), PBTZ169

EXPERIMENTAL

Single dose of PBTZ169: 1280 mg fasted

Drug: PBTZ169 1280 mg SD

Cohort 5 (C5), PBTZ169

EXPERIMENTAL

Multiple administration of PBTZ169: 1280 mg once a day after meal for 14 days

Drug: PBTZ169 1280 mg MD

Interventions

PBTZ169 640 mg OD DRUG

Two administrations once a day with a wash-out period: food effect

Also known as: Macozinone (PBTZ169)

Cohort 1 (C1A), PBTZ169; Cohort 1 (C1B), PBTZ169

PBTZ169 640 mg BiD DRUG

Twice a day fasted; 1 day of administration

Also known as: Macozinone (PBTZ169)

Cohort 3 (C3), PBTZ169

PBTZ169 960 mg SD DRUG

Once a day fasted

Also known as: Macozinone (PBTZ169)

Cohort 2 (C2), PBTZ169

PBTZ169 1280 mg SD DRUG

Once a day fasted

Also known as: Macozinone (PBTZ169)

Cohort 4 (C4), PBTZ169

PBTZ169 1280 mg MD DRUG

Once a day after meal, 14 doses

Also known as: Macozinone (PBTZ169)

Cohort 5 (C5), PBTZ169

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent from the volunteer.
• Men and women aged 18-45 years, inclusive.
• Body mass index of 18.5-30 kg/m2.
• 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).
• Negative results of tests for human immunodeficiency virus (HIV), syphilis, hepatitis B (Hbs Ag) and hepatitis C (antibodies to HCV).
• Ability to comply with all the requirements of the protocol in the opinion of the investigator.
• 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.

You may not qualify if:

• History of allergies, including at least one episode of allergy to medications.
• Chronic diseases of the cardiovascular, bronchopulmonary, neuroendocrine systems, ENT, as well as diseases of the gastrointestinal tract, liver, kidneys, blood, skin.
• Hypolactasia (lactose intolerance, lactase deficiency) or glucose-galatose malabsorption in medical history.
• Chronic eye diseases except for myopia, hypermetropia and astigmatism of mild and moderate severity.
• Surgeries on the gastrointestinal tract (except for appendectomy done more than 1 year before screening).
• Regular administration or use (including externally) of hormonal agent for more than 1 week less than 45 days before screening
• Regular administration of medicinal products less than 4 weeks before screening.
• Use of medicinal products that have a pronounced effect on liver function or hemodynamics (barbiturates, omeprazole, cimetidine, etc.) less than 30 days before screening.
• Positive test for narcotics and psychotropic products.
• 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).
• Heart rate (according to ECG) after resting in supine position for at least 5 minutes above 90 bpm or below 60 bpm.
• Blood donation (450 mL of blood or plasma and more) less than 3 months before the screening.
• Acute infectious diseases less than 4 weeks before screening.
• 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.
• Mental diseases.

Sponsors & Collaborators

• Nearmedic Plus LLC: lead

Study Sites (1)

Clinical hospital at the Yaroslavl station of the Open Joint Stock Company Russian Railways

Yaroslavl, 150030, Russia

Location

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Multidrug-Resistant; Extensively Drug-Resistant Tuberculosis

Interventions

macozinone; BID protein, human

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Viсtoria Shcherbakova
• Organization: Nearmedic Plus

Viktoriya.Shcherbakova@nearmedic.ru

+7 (495) 741 49 89

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2019
• First Posted: November 4, 2019
• Study Start: July 3, 2018
• Primary Completion: November 23, 2018
• Study Completion: February 1, 2019
• Last Updated: February 28, 2020
• Results First Posted: February 28, 2020

Record last verified: 2020-02

Locations

RU (1)