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TuberculosisPhase 2NCT03334734

Phase 2a Study of PBTZ169

A Phase 2 study testing PBTZ169 and Isoniazid in people with Tuberculosis, run by Nearmedic Plus LLC.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Tuberculosis
What is being tested?
PBTZ169 and Isoniazid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
No sites listed yet
Study dates
16 Dec 2016to 22 Feb 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

About this study

Official title: 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

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

Read the detailed description

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.

Conditions
Tuberculosis
Being tested
PBTZ169, Isoniazid
Keywords
Tuberculosis, PBTZ169, antimycobacterial
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PBTZ169Drug

    Once a day for 14 days

  • IsoniazidDrug

    Once a day for 14 days

Study groups in NCT03334734
Study groupRoleWhat they receive
PBTZ169, 160 mgExperimental2 capsules 80 mg of PBTZ169 once a day for 14 days
Receives: Drug: PBTZ169
PBTZ169, 320 mgExperimental4 capsules 80 mg of PBTZ169 once a day for 14 days
Receives: Drug: PBTZ169
PBTZ169, 640 mgExperimental8 capsules 80 mg of PBTZ169 once a day for 14 days
Receives: Drug: PBTZ169
Isoniazid, 600 mgActive comparator2 tablets 300 mg of Isoniazid once a day for 14 days
Receives: Drug: Isoniazid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Early Bactericidal Activity (0-14)

    Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): agar inoculation, the mean of two measurements at the Visit

    Measured: 14 days after the onset of monotherapy

  2. Early Bactericidal Activity (0-14)

    Early bactericidal activity 14 days from the monotherapy start date (EBA 0-14): PCR, the mean of two measurements at the Visit

    Measured: 14 days after the onset of monotherapy

Secondary outcomes (25)

  1. Early Bactericidal Activity (0-2)

    EBA (0-2): agar inoculation, the mean of two measurements at the Visit

    Measured: 2 days after the onset of monotherapy

  2. Early Bactericidal Activity (0-7)

    EBA (0-7): agar inoculation, the mean of two measurements at the Visit

    Measured: 7 days after the onset of monotherapy

  3. Early Bactericidal Activity (0-2)

    EBA (0-2): PCR, the mean of two measurements at the Visit

    Measured: 2 days after the onset of monotherapy

  4. Early Bactericidal Activity (0-7)

    EBA (0-7): PCR, the mean of two measurements at the Visit

    Measured: 7 days after the onset of monotherapy

  5. Peak Plasma Concentration (Сmax) of PBTZ169

    Peak plasma concentration (Сmax) of PBTZ169 for multiple dosing

    Measured: Up to 72 hours after the last drug administration

  6. Minimal Plasma Concentration (Сmin) of PBTZ169

    Minimal plasma concentration (Сmin) of PBTZ169: concentration measurement following single dosing

    Measured: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)

  7. Residual Concentration (Ctrough) of PBTZ169

    Residual concentration (Ctrough) of PBTZ169, measured 24 hours after the first dose administration, prior to the last dose, and 24 hours after the last dose

    Measured: Up to 72 hours after the last drug administration

  8. Minimal Plasma Concentration (Сmin) of PBTZ169

    Minimal plasma concentration (Сmin) of PBTZ169: multiple dosing

    Measured: Up to 72 hours after the last drug administration

  9. Time to Reach Maximum Concentration (Tmax) of PBTZ169

    Time to reach maximum concentration (Tmax) of PBTZ169 after single oral administration in different doses

    Measured: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)

  10. Time to Reach Maximum Concentration (Tmax) of PBTZ169

    Time to reach maximum concentration (Tmax) of PBTZ169 after multiple oral administration in different doses

    Measured: Up to 72 hours after the last drug administration

  11. AUC(0-24)

    Area under the plasma concentration of PBTZ169 versus time curve in frames [0-24 hours]

    Measured: Up to 24 hours after the first drug administration

  12. Peak Plasma Concentration (Сmax) of PBTZ169

    Peak plasma concentration (Сmax) of PBTZ169: concentration measurement following single dosing

    Measured: for single dosing , Day 1 (24 h after 1st dose of PBTZ169)

  13. AUC(0-24)

    Area under the plasma concentration of PBTZ169 versus time curve in frames [0-24 hours] for the last dosing (Day 14)

    Measured: Up to 24 hours after the last drug administration

  14. AUC (0-t)

    Area under the plasma concentration of PBTZ169 versus time curve in frames [0-last concentration above lower limit of quantification (LLoQ)]

    Measured: Up to 72 hours after the last drug administration

  15. AUC(0-∞) of PBTZ169

    Area under the plasma concentration versus time curve in frames [0-∞]

    Measured: Up to 72 hours after the last drug administration

  16. Accumulation Ratios for the PK Parameters AUC(0 -24)

    Accumulation ratios for the PK parameter AUC(0 -24): AUC(0- 24,ss)/AUC(0 -24), Day 1, on the original scale

    Measured: 24 hours after the first and the last drug administration

  17. Average Concentration (Css,av) of PBTZ169

    Average steady-state concentration in the dosing interval following multiple dosing was evaluated as the ratio AUC0 24/τ (τ = the dosing interval)

    Measured: Up to 72 hours after the last drug administration

  18. Fluctuations (%) in the Dosing Interval

    Fluctuations (%) in the dosing interval after multiple dosing ((Cmax - Cmin) × 100%/Css,av)

    Measured: Up to 72 hours after the last drug administration

  19. Total (Plasma) Clearance (Clt) of PBTZ169

    Clt/F (apparent total clearance following single and multiple oral administration) was calculated using the following formula:

    Cl_t/F=D/AUC where D is the daily dose of the drug.

    Measured: 24 hours after the first drug administration

  20. Total (Plasma) Clearance (Clt) of PBTZ169

    Clt/F (apparent total clearance following single and multiple oral administration) was calculated using the following formula:

    Cl_t/F=D/AUC where D is the daily dose of the drug.

    Measured: 24 hours after the last drug administration

  21. Volume of Distribution (Vd) of PBTZ169

    Distribution volume Vd for a dosing interval of 72 hours after the last dose

    Measured: Up to 72 hours after the last drug administration

  22. Plasma Half-life Time (T1/2) of PBTZ169

    Measured: 24 hours after the fist drug administration

  23. Plasma Half-life Time (T1/2) of PBTZ169

    Measured: 24 hours after the last drug administration

  24. Elimination Constant (Kel) of PBTZ169

    Apparent terminal elimination rate constant was evaluated based on the regressional dependence of log-transformed concentrations ln(C) on time for the terminal log- linear part of the concentration-time curve.

    Measured: 24 hours after the first drug administration

  25. Elimination Constant (Kel) of PBTZ169

    Apparent terminal elimination rate constant was evaluated based on the regressional dependence of log-transformed concentrations ln(C) on time for the terminal log- linear part of the concentration-time curve.

    Measured: 72 hours after the last drug administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2017
  2. Study start16 Dec 2016
  3. Primary completion10 Sep 2017
  4. Study completion22 Feb 2018

Why it stopped: Very slow enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03334734
Sponsor's protocol ID
PBTZ169-A15-C2A-1
Status last verified
Feb 2020
First submitted
3 Nov 2017
Last updated
9 Mar 2020
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PBTZ169 and Isoniazid in people with Tuberculosis, run by Nearmedic Plus LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Early Bactericidal Activity (0-14) (time frame: 14 days after the onset of monotherapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03334734.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2020.

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Phase 2a Study of PBTZ169 (NCT03334734) | AzTrials