- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04670120
Early Bactericidal Activity Safety Pulmonary Tuberculosis Pyrifazimine (TBI-166)
Evaluation of Early Bactericidal Activity and Safety in Pulmonary Tuberculosis With Pyrifazimine (TBI-166)
The new drug pyrifazimine (previous name: TBI-166) developed by the Institute of Materia Medica of the Chinese Academy of Medical Sciences which is Beijing Union Pharmaceutical Second Factory relied on is obtained by retaining the key skeleton of the lead drug clofazimine which can exert its efficacy and modification by introducing moderate polar groups structural. While the drug has strong activity against tuberculosis-sensitive bacteria and drug-resistant bacteria in vivo and in vitro, its pharmacokinetic properties and skin staining side effects have been significantly improved compared with the lead drugs, so that the drug can achieve the goal that reducing fat solubility, accelerating metabolism in the body, reducing skin staining and reducing side effects. In addition, pyrifazimine has a weak effect on liver drug enzymes, and is suitable for combined use in the clinical treatment of tuberculosis. The development of the drug is expected to provide a new method for the clinical treatment of drug-resistant tuberculosis, benefit patients, and produce good social benefits.
In November 2016, the new anti-drug-resistant tuberculosis drug pyrifazimine and its tablets (formerly chemical drug registration classification 1.1) obtained the drug clinical approval issued by the CFDA (batch number: 2016L10025/2016L09987), and were approved the clinical stage research that development of drug-resistant tuberculosis adaptation.
In accordance with relevant requirements of drug registration regulations, technical guidelines, etc., this project has completed the safety, tolerability, and pharmacokinetic clinical trials of a single dose of pyrifazimine tablets in healthy subjects, i.e. Phase Ia clinical trials test.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 101149
- Beijing Chest Hospital
-
-
Henan
-
Zhengzhou, Henan, China, 450000
- Zhengzhou Sixth People's Hospital
-
-
Shandong
-
Jinan, Shandong, China, 250013
- Shandong Chest Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
(Those who must meet all the selection criteria can enter the group)
- People who volunteer to participate in this trial and sign an informed consent form;
- The range of the age is from 18 to 65 years old, regardless of gender;
- The weight range of the patient who wear lightweight clothing and no shoes is from 40 to 90 Kg;
- The patient is diagnosed with (initial treatment) tuberculosis, and the untreated sputum smear is 2+ or 2 times 1+ or more;
- Chest x-ray examination results are consistent with tuberculosis;
- Molecular tests show positive for Mycobacterium tuberculosis (e.g. GeneXpert or Hain) or positive for sputum culture;
- Women in the reproductive period have a negative urine pregnancy test and agree to use high-efficiency contraception during the study period;
- Male patients must agree to use appropriate contraceptive methods.
Exclusion Criteria:
(Meet any of the following criteria will be excluded)
- Those who cannot tolerate treatment delay;
- Those who have used any drugs that are effective against Mycobacterium tuberculosis within 3 months before screening;
- History of allergy to clofazimine, rifamycin and its derivatives, isoniazid, pyrazinamide or ethambutol;
- Use any drugs or substances known to be strong inhibitors or inducers of cytochrome P450 enzymes within 30 days before administration (Including but not limited to quinidine, tyramine, ketoconazole, fluconazole, testosterone, quinine, progesterone, Methitione, phenpromazine, doxorubicin, trilithomycin, erythromycin, cocaine, furanilide, cimetidine, dextromethorphan);
- Resistance to isoniazid and rifampicin;
- Any disease or symptom that contradicts the use of rifampicin, isoniazid, pyrazinamide or ethambutol;
- Severe extrapulmonary tuberculosis (blood disseminated tuberculosis, digestive system tuberculosis, genitourinary tuberculosis, bone and joint tuberculosis, tuberculosis meningitis, etc.);
- There is evidence of silicosis, pulmonary fibrosis or other lung diseases considered by researchers to be serious (except tuberculosis);
- The patient has chronic obstructive pulmonary disease or asthma;
- Any clinically relevant concomitant circumstances or renal impairment characterized by serum creatinine level ≥1.5xULN, or liver damage with ALT and/or AST level ≥3×ULN and/or GGT level ≥3×ULN within the laboratory reference range;
- History of alcohol abuse [weekly alcohol intake is greater than 21 units/week (male) and 14 units/week (female) (1 unit=360mL beer; or 150mL glucose wine; or 45mL white wine)], or the subject is unwilling to stop drinking from 24 hours before the start of the study to the end of the study, or had a positive alcohol breath test at the time of enrollment;
- Subjects with liver, kidney, metabolism, autoimmune diseases, neurological, mental, blood system diseases, malignant tumors, long-term immunosuppressive agents;
- People with a history of drug abuse or a positive urine drug screening;
- Screening positive for hepatitis B, HIV, HCV virus and Treponema pallidum antibody;
- Those who have a history of fainting needles and are judged to be clinically significant by the investigator;
- Participated in clinical research of other drugs or devices three months before the start of the trial;
- The subject has the following characteristics at the time of screening (according to the measurement and reading of the central electrocardiogram):
- The QT/QTc interval is significantly prolonged, for example, the QTcF (Fridericia correction) or QTcB (Bazett correction) interval is confirmed to be >450 ms during screening;
- Has a history of Ventricular tachycardia torsades de pointes, such as heart failure, hypokalemia, long QT syndrome, etc.;
- Uses any drug known to extend the QTc interval 30 doses before the medication. (Not limited to amiodarone, bepridil, chloroquine, chlorpromazine, cisapride, cyclobenzaprine, clarithromycin, dipyrazine, doperidol, erythromycin, fluorine alcohol, Haloperidol, ibutilide, levamisole, methadone, mesalamide, pimozine, procaine, quinine, sotalol, sparfloxacin, thiazide);
- The investigator judges that any ECG abnormalities of clinical significance.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: First group
Pyfazimine 100mg group, 12 cases.
|
The new drug pyrifazimine (previous name: TBI-166) is obtained by retaining the key skeleton of the lead drug clofazimine which can exert its efficacy and modification by introducing moderate polar groups structural. While the drug has strong activity against tuberculosis-sensitive bacteria and drug-resistant bacteria in vivo and in vitro, its pharmacokinetic properties and skin staining side effects have been significantly improved compared with the lead drugs, so that the drug can achieve the goal that reducing fat solubility, accelerating metabolism in the body, reducing skin staining and reducing side effects. In November 2016, the new anti-drug-resistant tuberculosis drug pyrifazimine and its tablets obtained the drug clinical approval issued by the CFDA, and were approved the clinical stage research that development of drug-resistant tuberculosis adaptation. |
Experimental: Second group
Pyfazimine 200mg group, 12 cases.
|
The new drug pyrifazimine (previous name: TBI-166) is obtained by retaining the key skeleton of the lead drug clofazimine which can exert its efficacy and modification by introducing moderate polar groups structural. While the drug has strong activity against tuberculosis-sensitive bacteria and drug-resistant bacteria in vivo and in vitro, its pharmacokinetic properties and skin staining side effects have been significantly improved compared with the lead drugs, so that the drug can achieve the goal that reducing fat solubility, accelerating metabolism in the body, reducing skin staining and reducing side effects. In November 2016, the new anti-drug-resistant tuberculosis drug pyrifazimine and its tablets obtained the drug clinical approval issued by the CFDA, and were approved the clinical stage research that development of drug-resistant tuberculosis adaptation. |
Experimental: Third group
Pyfazimine 300mg group, 12 cases.
|
The new drug pyrifazimine (previous name: TBI-166) is obtained by retaining the key skeleton of the lead drug clofazimine which can exert its efficacy and modification by introducing moderate polar groups structural. While the drug has strong activity against tuberculosis-sensitive bacteria and drug-resistant bacteria in vivo and in vitro, its pharmacokinetic properties and skin staining side effects have been significantly improved compared with the lead drugs, so that the drug can achieve the goal that reducing fat solubility, accelerating metabolism in the body, reducing skin staining and reducing side effects. In November 2016, the new anti-drug-resistant tuberculosis drug pyrifazimine and its tablets obtained the drug clinical approval issued by the CFDA, and were approved the clinical stage research that development of drug-resistant tuberculosis adaptation. |
Active Comparator: Forth group
Pyrazinamide 1500mg group, 10 cases.
|
The new drug pyrifazimine (previous name: TBI-166) is obtained by retaining the key skeleton of the lead drug clofazimine which can exert its efficacy and modification by introducing moderate polar groups structural. While the drug has strong activity against tuberculosis-sensitive bacteria and drug-resistant bacteria in vivo and in vitro, its pharmacokinetic properties and skin staining side effects have been significantly improved compared with the lead drugs, so that the drug can achieve the goal that reducing fat solubility, accelerating metabolism in the body, reducing skin staining and reducing side effects. In November 2016, the new anti-drug-resistant tuberculosis drug pyrifazimine and its tablets obtained the drug clinical approval issued by the CFDA, and were approved the clinical stage research that development of drug-resistant tuberculosis adaptation. |
Active Comparator: Fifth group
Pyfazimine 200mg + Pyrazinamide 1500mg group, 10 cases.
|
The new drug pyrifazimine (previous name: TBI-166) is obtained by retaining the key skeleton of the lead drug clofazimine which can exert its efficacy and modification by introducing moderate polar groups structural. While the drug has strong activity against tuberculosis-sensitive bacteria and drug-resistant bacteria in vivo and in vitro, its pharmacokinetic properties and skin staining side effects have been significantly improved compared with the lead drugs, so that the drug can achieve the goal that reducing fat solubility, accelerating metabolism in the body, reducing skin staining and reducing side effects. In November 2016, the new anti-drug-resistant tuberculosis drug pyrifazimine and its tablets obtained the drug clinical approval issued by the CFDA, and were approved the clinical stage research that development of drug-resistant tuberculosis adaptation. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EBA
Time Frame: The change of TB bacterium burden in sputum from Day 0 to Day 7 and/or Day 14
|
Early bactericidal activity (EBA), counted by daily log (CFU) change
|
The change of TB bacterium burden in sputum from Day 0 to Day 7 and/or Day 14
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GCP-TB-Pyrifazimine (TBI-166)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Sensitive Pulmonary Tuberculosis
-
Global Alliance for TB Drug DevelopmentRecruitingDrug Sensitive Tuberculosis | Pulmonary Tuberculosis | Pulmonary TBPhilippines, South Africa, Tanzania, Georgia, Uganda
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis, Pulmonary, Drug Sensitive | Tuberculosis, Pulmonary, Multi Drug-resistantSouth Africa, Zambia, Georgia, Philippines, Kenya, Malaysia, Tanzania, Uganda
-
Centers for Disease Control and PreventionCompletedSmear Positive, Pan-sensitive, Pulmonary TuberculosisUnited States, South Africa, Uganda
-
Global Alliance for TB Drug DevelopmentCompleted
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis | Tuberculosis, Pulmonary | Pulmonary Disease | Multi Drug Resistant Tuberculosis | Drug Sensitive Tuberculosis | Drug-resistant Tuberculosis | Mycobacterium Tuberculosis InfectionUnited States
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis | Tuberculosis, Pulmonary | Pulmonary Disease | Multi Drug Resistant Tuberculosis | Drug Sensitive Tuberculosis | Drug-resistant Tuberculosis | Mycobacterium Tuberculosis InfectionUnited States
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis | Tuberculosis, Pulmonary | Tuberculosis, Multidrug-Resistant | Tuberculosis, MDR | Drug-Resistant TuberculosisTanzania, Georgia, Russian Federation, Brazil, Malaysia, Philippines, South Africa, Uganda
-
Foundation for Innovative New Diagnostics, SwitzerlandInstitute of Tropical Medicine, Belgium; Research Center Borstel; National Institute...CompletedMultidrug-Resistant Tuberculosis | Isoniazid Resistant Pulmonary Tuberculosis | Rifampicin Resistant Tuberculosis | Pulmonary Tuberculoses
-
Universiteit AntwerpenAurum Institute; University of Stellenbosch; University of the Free State; Free...RecruitingDrug-resistant Tuberculosis | Rifampicin Resistant Tuberculosis | Pulmonary Tuberculoses | Multidrug Resistant TuberculosisSouth Africa
-
Tjip van der WerfGadjah Mada University; The Enose Company, Zutphen the NetherlandsCompletedPulmonary Tuberculosis Suspected | Other Specified Chronic Obstructive Pulmonary Disease | Pulmonary Tuberculosis TB (+) Histology, (-) BacteriologyIndonesia
Clinical Trials on Pyrifazimine (TBI-166)
-
Terumo Europe N.V.RecruitingHepatocellular CarcinomaGermany
-
Poniard PharmaceuticalsTerminated
-
UMC UtrechtErasmus Medical Center; Terumo CorporationRecruitingHepatocellular Carcinoma Non-resectableNetherlands
-
Radboud University Medical CenterTerumo Medical Corporation; Quirem Medical B.V.Recruiting
-
UMC UtrechtErasmus Medical Center; Dutch Cancer Society; Quirem Medical B.V.CompletedHepatocellular Carcinoma | Hepatocellular Carcinoma Non-resectableNetherlands
-
UMC UtrechtCompletedLiver Tumors | Liver MetastasisNetherlands
-
Leiden University Medical CenterMedtronic; ZonMw: The Netherlands Organisation for Health Research and Development and other collaboratorsCompletedHCC | Early Stage HCCNetherlands
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis | Tuberculosis, PulmonaryUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)Completed
-
Global Alliance for TB Drug DevelopmentCompletedTuberculosis | Tuberculosis, PulmonaryUnited States