Clinical Study of JDB0131 Benzenesulfonate Tablets in Patients With Drug-sensitive Pulmonary Tuberculosis

Phase 2

Recruiting

• Conditions: Drug-resistant Tuberculosis
• Interventions: Drug: JDB0131; Drug: Ethylpyrazine rifampicide (II); Drug: Delamanid

• Registration Number: NCT06224036
• Lead Sponsor: Beijing Chest Hospital

Brief Summary

A randomized, open, drug controlled design of experiments was used to evaluate the early bactericidal activity, safety, tolerance and pharmacokinetic characteristics of JDB0131 benzenesulfonate tablet taken orally by drug sensitive pulmonary tuberculosis patients. Five groups are proposed to be set up in this test (JDB0131 benzenesulfonate 100mg BID, JDB0131 benzenesulfonate 200mg QD, JDB0131 benzenesulfonate 200mg BID, anti tuberculosis drug fixed dose composite dosage QD is determined according to the weight of the study participants, and delamanid 100mg BID)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-09
• Study Start: 2023-10-31
• Status Verified: 2024-01
• Study First Submitted QC: 2024-01-16
• Last Update Submitted: 2024-01-16
• Study First Posted: 2024-01-25
• Last Update Posted: 2024-01-25
• Primary Completion: 2024-03-31
• Study Completion: 2024-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• (Those who must meet all the selection criteria can enter the group)

  1. Age of study participants: 18 years old≤ age ≤ 65 years old, male or female;
  2. Study participant weight: 40kg≤ body weight≤90kg
  3. Patients with clinically confirmed pulmonary tuberculosis, and have not received anti-tuberculosis therapy within 2 years, at least one positive sputum acid-fast bacilli smear (AFB at least 1+);
  4. Be willing to provide a blood sample for HIV testing;
  5. Non-lactating and non-pregnant women who agree to use highly effective contraception throughout the study period, and male study participants must agree to use appropriate contraceptive methods throughout the study period;
  6. The study participants fully understand the purpose, nature, methods and possible adverse reactions of the trial, voluntarily act as research participants, and sign informed consent;
  7. Those who are willing to complete the test according to the requirements of the program.

Exclusion Criteria

• (Meet any of the following criteria will be excluded)

  1. Rifampicin resistance;
  2. Positive for human immunodeficiency virus (HIV) antibodies; positive for hepatitis B surface antigen (HBsAg); positive for hepatitis C virus (HCV) antibodies; positive for treponemal antibodies;
  3. Clear hepatobiliary disease, including but not limited to chronic active hepatitis and/or severe hepatic insufficiency; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal; Total serum bilirub (TBIL) > 2 times the upper limit of normal;
  4. Have a history of kidney disease or manifestations related to renal disease: 1) history of unstable or rapidly progressive kidney disease; 2) Moderate/severe renal impairment or end-stage renal disease (eGFR<60mL/min/1.73m2); 3) Serum creatinine (Cr) ≥ 133 μmol/L (1.5 mg/mL) in men, Cr ≥ 124 μmol/L (1.4 mg/mL) in women;
  5. Have a family history of QT prolongation syndrome or are taking drugs that cause QT interval prolongation, such as: quinidine, procainamide, amiodarone, sotalol, etc.;
  6. ECG showed the following abnormalities: 1) QTcF>450 ms (corrected by Fridericia formula); 2) pathological Q wave (defined as >40ms or depth >0.4-0.5mV); 3) ECG suggests pre-excitation syndrome; 4) ECG suggests left bundle branch block or right bundle branch block; 5) ECG shows second- or third-degree heart block; 6) QRS duration > 120ms indoor conduction delay; 7) Sinus heart rate < bradycardia of 50bpm;
  7. Those who have any of the following cardiovascular diseases or other conditions within 6 months before enrollment: 1) myocardial infarction; 2) Cardiac surgery or coronary revascularization (coronary artery bypass grafting/percutaneous transluminal coronary angioplasty); 3) unstable angina; 4) congestive heart failure (New York Cardiology Society Cardiac Function Class III or IV); 5) transient ischemic attack or severe cerebrovascular disease;
  8. Anyone who is unable to comply with the uniform diet due to allergies or special dietary requirements;
  9. Those with a history of gastrointestinal surgery or resection that may affect the absorption and/or excretion of oral medications;
  10. Those who have abnormal ophthalmic examination during the screening period and are judged by the investigator to be unsuitable for participating in this trial;
  11. Depression: those with a score higher than 7 on the Hamilton Depression Scale (17 items, see Appendix 2);
  12. Those who are judged to have any unstable or severe cardiovascular, renal, liver, hematology, tumor, endocrine metabolism, psychiatric or rheumatic diseases and therefore consider them unsuitable to participate in this trial;
  13. Those who cannot control the consumption of alcohol or alcohol-containing products from 48 h before administration to the completion of the last pharmacokinetic blood sample collection, and do not consume any food or beverage containing or metabolizing caffeine or xanthines (such as coffee, strong tea, cola, chocolate);
  14. Patients who have used other clinical trial study drugs within 3 months prior to administration;
  15. Patients with a history of alcohol dependence or substance abuse within 6 months prior to screening, which the investigator believes may affect the safety of study participants and affect trial adherence;
  16. Use of psychotropic drugs such as barbiturates, opioids, and phenothiazines within 30 days;
  17. Chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid therapy, cumulative use for more than 4 weeks in the 3 months prior to enrollment;
  18. Those who are allergic to any investigational drug or related substances confirmed by the clinical judgment of the investigator;
  19. Strong inducers or inhibitors of cytochrome P450 enzyme (e.g., carbamazepine, phenytoin, rifampicin, clarithromycin, ritonavir, ketoconazole, itraconazole, etc.) within 30 days before treatment;
  20. Women with a positive pregnancy test or breastfeeding during screening;
  21. Those who received live attenuated vaccine within 4 weeks before the study drug (except inactivated influenza vaccine such as seasonal influenza vaccine for injection);
  22. Any condition that, in the judgment of the investigator, affects the study participant's adherence to the study protocol, or incorporates any serious medical or psychological condition that may affect the interpretation of efficacy and safety data, or that the study participant's participation in the trial may affect his or her own safety.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
First group	JDB0131	JDB0131 Benzenesulfonate tablets,100mg BID group,12 cases
Forth group	Ethylpyrazine rifampicide (II)	Ethylpyrazine rifampicide (II) QD group,8 cases
Second group	JDB0131	JDB0131 Benzenesulfonate tablets 200mg QD group,12 cases
Third group	JDB0131	JDB0131 Benzenesulfonate tablets 200mg BID group,12 cases
Fifth group	Delamanid	Delamanid Tablets 100mg BID group,8 cases

Primary Outcome Measures

Name	Time	Method
EBA	he change of TB bacterium burden in sputum from Day 0 to Day 2 and/or Day 14	Early bactericidal activity (EBA), counted by daily log (CFU) change

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Immediately Reportable Events (IREs)	average of 6 month	An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-participant hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above. The following were considered as IREs- serious adverse events (SAEs), pregnancies in trial participants or their partners, and all events involving overdose, misuse and abuse.problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the investigator.
Rac（Cmax）	Day 0 to Day 21	Ratio of Cmax,ss at day 14 to Cmax at day 1
Rac（AUC）	Day 0 to Day 21	AUC0-12,ss at day 14 compared to AUC0-12 at day 1
Cmax	Day 0 to Day 21	Maximal Peak Plasma Concentration for JDB0131
Vd,ss	Day 0 to Day 21	Apparent volume of distribution for JDB0131
ECG	an average of 6 month	ECG QT Interval
AUC0-24h	Day 0 to Day 21	Area under plasma concentration time curve from initial administration to 12 hours for JDB0131
Css,min	Day 0 to Day 21	Steady-state valley concentration for JDB0131
t1/2,ss	Day 0 to Day 21	Elimination half life for JDB0131
Percentage of Participants With Adverse Events (AEs)	average of 6 month	An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the investigator.
Safe tolerance	through study completion, an average of 6 month	Eye examination and depression scale scores
Tmax	Day 0 to Day 21	Time to Reach Maximal Peak Plasma Concentration for JDB0131
T Tss,max	Day 0 to Day 21	Steady state peak time for JDB0131
Css,max	Day 0 to Day 21	Steady state peak concentration for JDB0131
Css,avg	Day 0 to Day 21	Mean steady-state blood drug concentration for JDB0131
AUC0-12,ss	Day 0 to Day 21	Area under the plasma concentration time curve from the last administration to 12 hours for JDB0131
AUC0-t,ss	Day 0 to Day 21	Area under the plasma concentration-time curve from the last dose to the last measurable concentration time "t" for JDB0131
AUC0-∞,ss	Day 0 to Day 21	Area under the plasma concentration-time curve from the last dose extrapolated to infinity for JDB0131
CL,ss	Day 0 to Day 21	Oral clearance for JDB0131
Fluctuation coefficient	Day 0 to Day 21	Percent fluctuation at steady state = 100 \* (Css, max - Css, min) / Css, avg.

Trial Locations

Locations (2)

Wuhan Chest Hospital (Wuhan Institute For Tuberculosis Control); 🇨🇳 Wuhan, Hubei, China

West China Hospital, Sichuan University; 🇨🇳 Chendu, Sichuan, China