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TerminatedNCT03334734Updated Mar 9, 2020Results posted

Phase 2a Study of PBTZ169

A Phase 2 interventional study of PBTZ169 and Isoniazid in Tuberculosis, sponsored by Nearmedic Plus LLC. Terminated. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-03-09.

Sponsored by Nearmedic Plus LLC · Phase 2, Interventional, and Treatment

Why this study was terminated
Very slow enrollment

From the registry’s dates

  • Registered 10 months after the study started (first participant enrolled Dec 2016, registered Nov 2017).
Phase
Phase 2
Study type
Interventional
Enrollment
16
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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

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.

02

Conditions studied

  • Tuberculosis

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Keywords

  • Tuberculosis
  • PBTZ169
  • antimycobacterial
03

In context

Tuberculosis

1,170 studies on the registry are indexed under Tuberculosis; 175 are open to participants now.

This study's enrollment of 16 is below the median of 150 across 820 interventional studies indexed under Tuberculosis.

Browse Tuberculosis studies →

Lead sponsor

Nearmedic Plus LLC is the lead sponsor of 9 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Written 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
  • of 18.5-25 kg/m2
  • Ability, according to investigators opinion, to comply with all requirements of the protocol

  • Agreement to use double 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

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 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):

    • (AST) level > 2.0 x upper limit of the norm
    • Alanine aminotransferase (ALT) level > 2.0 x upper limit of norm
    • General 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 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
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

BMI (body mass index)

Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.

What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • Experimental
    PBTZ169, 160 mg

    2 capsules 80 mg of PBTZ169 once a day for 14 days

    Drug: PBTZ169

  • Experimental
    PBTZ169, 320 mg

    4 capsules 80 mg of PBTZ169 once a day for 14 days

    Drug: PBTZ169

  • Experimental
    PBTZ169, 640 mg

    8 capsules 80 mg of PBTZ169 once a day for 14 days

    Drug: PBTZ169

  • Active comparator
    Isoniazid, 600 mg

    2 tablets 300 mg of Isoniazid once a day for 14 days

    Drug: Isoniazid

Interventions

06

What researchers measure

Primary outcomes

  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

    Time frame: 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

    Time frame: 14 days after the onset of monotherapy

Secondary outcomes

  1. Early Bactericidal Activity (0-2)

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 7 days after the onset of monotherapy

  5. Peak Plasma Concentration (Сmax) of PBTZ169

    Peak plasma concentration (Сmax) of PBTZ169 for multiple dosing

    Time frame: 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

    Time frame: 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

    Time frame: Up to 72 hours after the last drug administration

  8. Minimal Plasma Concentration (Сmin) of PBTZ169

    Minimal plasma concentration (Сmin) of PBTZ169: multiple dosing

    Time frame: 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

    Time frame: 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

    Time frame: 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 \[0-24 hours\]

    Time frame: 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

    Time frame: 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)

    Time frame: 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 \[0-last concentration above lower limit of quantification (LLoQ)\]

    Time frame: Up to 72 hours after the last drug administration

  15. AUC(0-∞) of PBTZ169

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

    Time frame: 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

    Time frame: 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)

    Time frame: 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)

    Time frame: 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.

    Time frame: 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.

    Time frame: 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

    Time frame: Up to 72 hours after the last drug administration

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

    Time frame: 24 hours after the fist drug administration

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

    Time frame: 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.

    Time frame: 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.

    Time frame: 72 hours after the last drug administration

07

Results

Posted Mar 9, 2020

Participant flow

Participant flow — Overall Study
MilestonePBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Started4471
Completed4451
Not completed0020

Outcome measures

PrimaryEarly 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

Time frame:
14 days after the onset of monotherapy
Reported as:
Mean · CFU per 1 mL of sputum
Early Bactericidal Activity (0-14)
CFU per 1 mL of sputumPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Early Bactericidal Activity (0-14)0.061 ± 0.0850.015 ± 0.0250.071 ± 0.1260.237 ± 0
PrimaryEarly 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

Time frame:
14 days after the onset of monotherapy
Reported as:
Mean · cell count per 1 mL of sputum
Early Bactericidal Activity (0-14)
cell count per 1 mL of sputumPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Early Bactericidal Activity (0-14)0.038 ± 0.081-0.014 ± 0.0480.097 ± 0.136-0.099 ± 0
SecondaryEarly Bactericidal Activity (0-2)

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

Time frame:
2 days after the onset of monotherapy
Reported as:
Mean · CFU per 1 mL of sputum
Early Bactericidal Activity (0-2)
CFU per 1 mL of sputumPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Early Bactericidal Activity (0-2)0.496 ± 0.6150.124 ± 0.095-0.003 ± 0.452-0.243 ± 0
SecondaryEarly Bactericidal Activity (0-7)

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

Time frame:
7 days after the onset of monotherapy
Reported as:
Mean · CFU per 1 mL of sputum
Early Bactericidal Activity (0-7)
CFU per 1 mL of sputumPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Early Bactericidal Activity (0-7)0.078 ± 0.1360.026 ± 0.0690.064 ± 0.1020.090 ± 0
SecondaryEarly Bactericidal Activity (0-2)

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

Time frame:
2 days after the onset of monotherapy
Reported as:
Mean · cell count per 1 mL of sputum
Early Bactericidal Activity (0-2)
cell count per 1 mL of sputumPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Early Bactericidal Activity (0-2)-0.110 ± 0.8720.007 ± 0.0840.085 ± 0.3970.627 ± 0
SecondaryEarly Bactericidal Activity (0-7)

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

Time frame:
7 days after the onset of monotherapy
Reported as:
Mean · cell count per 1 mL of sputum
Early Bactericidal Activity (0-7)
cell count per 1 mL of sputumPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Early Bactericidal Activity (0-7)-0.044 ± 0.076-0.004 ± 0.0810.116 ± 0.186-0.408 ± 0
SecondaryPeak Plasma Concentration (Сmax) of PBTZ169

Peak plasma concentration (Сmax) of PBTZ169 for multiple dosing

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · ng/ml
Peak Plasma Concentration (Сmax) of PBTZ169
ng/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Peak Plasma Concentration (Сmax) of PBTZ16934.4714 ± 18.6498122.0135 ± 96.3347101.3818 ± 31.3830
SecondaryMinimal Plasma Concentration (Сmin) of PBTZ169

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

Time frame:
for single dosing , Day 1 (24 h after 1st dose of PBTZ169)
Reported as:
Mean · ng/ml
Minimal Plasma Concentration (Сmin) of PBTZ169
ng/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Minimal Plasma Concentration (Сmin) of PBTZ1690.4985 ± 0.44750.2678 ± 0.33751.0275 ± 0.9101
SecondaryResidual 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

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · ng/ml
Residual Concentration (Ctrough) of PBTZ169
ng/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
24 hours after the first dose (Ctrough_SD24)0.7835 ± 0.68201.4116 ± 1.27121.8712 ± 0.9453
prior to the last dose (Ctrough_MD0)2.1610 ± 1.63324.9505 ± 1.405018.2674 ± 27.2441
24 hours after the last dose (Ctrough_MD24)1.4207 ± 1.01452.9274 ± 1.45355.2710 ± 2.5201
SecondaryMinimal Plasma Concentration (Сmin) of PBTZ169

Minimal plasma concentration (Сmin) of PBTZ169: multiple dosing

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · ng/ml
Minimal Plasma Concentration (Сmin) of PBTZ169
ng/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Minimal Plasma Concentration (Сmin) of PBTZ1691.4207 ± 1.01453.3889 ± 2.00014.9322 ± 2.4003
SecondaryTime to Reach Maximum Concentration (Tmax) of PBTZ169

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

Time frame:
for single dosing , Day 1 (24 h after 1st dose of PBTZ169)
Reported as:
Median · h
Time to Reach Maximum Concentration (Tmax) of PBTZ169
hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Time to Reach Maximum Concentration (Tmax) of PBTZ1691.250 (0.67 to 2.00)2.250 (1.00 to 6.00)2.000 (0.33 to 3.00)
SecondaryTime to Reach Maximum Concentration (Tmax) of PBTZ169

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

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Median · h
Time to Reach Maximum Concentration (Tmax) of PBTZ169
hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Time to Reach Maximum Concentration (Tmax) of PBTZ1692.000 (0.67 to 2.98)2.000 (1.00 to 6.00)1.500 (0.00 to 2.4)
SecondaryAUC(0-24)

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

Time frame:
Up to 24 hours after the first drug administration
Reported as:
Mean · ng*h/ml
AUC(0-24)
ng*h/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
AUC(0-24)93.604 ± 74.3008120.954 ± 44.7920237.153 ± 111.4025
SecondaryPeak Plasma Concentration (Сmax) of PBTZ169

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

Time frame:
for single dosing , Day 1 (24 h after 1st dose of PBTZ169)
Reported as:
Mean · ng/ml
Peak Plasma Concentration (Сmax) of PBTZ169
ng/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Peak Plasma Concentration (Сmax) of PBTZ16924.6543 ± 18.850635.5370 ± 23.498379.6684 ± 49.1865
SecondaryAUC(0-24)

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

Time frame:
Up to 24 hours after the last drug administration
Reported as:
Mean · ng*h/ml
AUC(0-24)
ng*h/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
AUC(0-24)113.293 ± 73.9862349.308 ± 282.1627502.895 ± 167.7201
SecondaryAUC (0-t)

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

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · ng*h/ml
AUC (0-t)
ng*h/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
AUC (0-t)113.259 ± 73.9728356.170 ± 282.0489502.075 ± 168.5111
SecondaryAUC(0-∞) of PBTZ169

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

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · ng*h/ml
AUC(0-∞) of PBTZ169
ng*h/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
AUC(0-∞) of PBTZ169141.855 ± 87.0391412.819 ± 299.2734568.581 ± 189.4584
SecondaryAccumulation 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

Time frame:
24 hours after the first and the last drug administration
Reported as:
Geometric mean · ratio
Accumulation Ratios for the PK Parameters AUC(0 -24)
ratioPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Accumulation Ratios for the PK Parameters AUC(0 -24)1.50 (0.81 to 2.76)2.35 (1.28 to 4.34)2.74 (1.58 to 4.73)
SecondaryAverage 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)

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · ng/ml
Average Concentration (Css,av) of PBTZ169
ng/mlPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Average Concentration (Css,av) of PBTZ169862.63 ± 606.973793.27 ± 212.270532.95 ± 325.436
SecondaryFluctuations (%) in the Dosing Interval

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

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · % (ratio)
Fluctuations (%) in the Dosing Interval
% (ratio)PBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Fluctuations (%) in the Dosing Interval32955.25 ± 18636.03724703.16 ± 19047.81116253.19 ± 7977.030
SecondaryTotal (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.

Time frame:
24 hours after the first drug administration
Reported as:
Mean · L/h
Total (Plasma) Clearance (Clt) of PBTZ169
L/hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Total (Plasma) Clearance (Clt) of PBTZ1693293.80 ± 3329.0262375.06 ± 759.2032935.49 ± 1382.371
SecondaryTotal (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.

Time frame:
24 hours after the last drug administration
Reported as:
Mean · L/h
Total (Plasma) Clearance (Clt) of PBTZ169
L/hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Total (Plasma) Clearance (Clt) of PBTZ1691393.31 ± 606.6761200.61 ± 899.7071259.77 ± 519.021
SecondaryVolume of Distribution (Vd) of PBTZ169

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

Time frame:
Up to 72 hours after the last drug administration
Reported as:
Mean · L
Volume of Distribution (Vd) of PBTZ169
LPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Volume of Distribution (Vd) of PBTZ1694.7206 ± 3.082814.5545 ± 11.756820.9540 ± 6.9883
SecondaryPlasma Half-life Time (T1/2) of PBTZ169
Time frame:
24 hours after the fist drug administration
Reported as:
Mean · h
Plasma Half-life Time (T1/2) of PBTZ169
hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Plasma Half-life Time (T1/2) of PBTZ16910.201 ± 4.631916.469 ± 9.566910.110 ± 2.1530
SecondaryPlasma Half-life Time (T1/2) of PBTZ169
Time frame:
24 hours after the last drug administration
Reported as:
Mean · h
Plasma Half-life Time (T1/2) of PBTZ169
hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Plasma Half-life Time (T1/2) of PBTZ16915.524 ± 4.003713.790 ± 2.32348.883 ± 2.5338
SecondaryElimination 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.

Time frame:
24 hours after the first drug administration
Reported as:
Mean · 1/h
Elimination Constant (Kel) of PBTZ169
1/hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Elimination Constant (Kel) of PBTZ1690.0797 ± 0.03710.0524 ± 0.02500.0708 ± 0.0126
SecondaryElimination 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.

Time frame:
72 hours after the last drug administration
Reported as:
Mean · 1/h
Elimination Constant (Kel) of PBTZ169
1/hPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mg
Elimination Constant (Kel) of PBTZ1690.0470 ± 0.01230.0515 ± 0.00980.0828 ± 0.0211

Adverse events

Collected over Collection and evaluation of safety data started at the Screening Visit (Day -10 to -1) after signing the informed consent form and was continued till the last visit of the patient within the study (Day 21+1). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
PBTZ169, 160 mg0/4 (0%)0/4 (0%)3/4 (75%)
PBTZ169, 320 mg0/4 (0%)0/4 (0%)3/4 (75%)
PBTZ169, 640 mg0/7 (0%)1/7 (14.3%)2/7 (28.6%)
Isoniazid, 600 mg0/1 (0%)0/1 (0%)0/1 (0%)
Most frequent serious events
Most frequent serious events
EventPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Spontaneously opened tuberculous paraproctitisGastrointestinal disorders0/40/41/70/1
Most frequent other events
Showing 10 of 13
Most frequent other events
EventPBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mg
Sinus arrhythmiaCardiac disorders1/40/40/70/1
Sinus tachycardiaCardiac disorders0/41/41/70/1
Wandering atrial pacemakerCardiac disorders1/40/40/70/1
HyperthermiaGeneral disorders1/40/40/70/1
Metabolic disorders found in ECGInvestigations0/41/40/70/1
QTc elongationInvestigations0/41/41/70/1
QTc(F) shorteningInvestigations0/41/40/70/1
HyperglycemiaMetabolism and nutrition disorders1/40/40/70/1
FeverInvestigations0/40/41/70/1
Repolarization disturbances in the V1 lead in ECGInvestigations0/40/41/70/1

Baseline characteristics

Age, Continuous
Age, Continuous(years)PBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mgTotal
Mean49.0 ± 13.048.8 ± 10.743.7 ± 14.841.0 ± 046.1 ± 12.3
Sex: Female, Male
Sex: Female, Male(Participants)PBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mgTotal
Female00202
Male445114
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mgTotal
American Indian or Alaska Native00000
Asian00000
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White447116
More than one race00000
Unknown or Not Reported00000
Region of Enrollment
Region of Enrollment(participants)PBTZ169, 160 mgPBTZ169, 320 mgPBTZ169, 640 mgIsoniazid, 600 mgTotal
Russia447116
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Study locations

No study locations are listed for this record.

09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

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Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Dec 2016 to primary completion in Sep 2017, 8 months.

Results were first posted in Mar 2020, 2 years 5 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 3, 2017
First posted
Nov 7, 2017
StartActual
Dec 16, 2016
Primary completionActual
Sep 10, 2017
CompletionActual
Feb 22, 2018
Results first posted
Mar 9, 2020
Last update
Mar 9, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Mar 9, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03334734
Lead sponsor
Nearmedic Plus LLC
Collaborators
OCT LLC
Responsible party
Sponsor
First posted
Nov 7, 2017
Start date
Dec 16, 2016
Primary completion
Sep 10, 2017
Completion
Feb 22, 2018
Results posted
Mar 9, 2020
Last update
Mar 9, 2020

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Macozinone

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