Clinical trial NCT06224036: Clinical Study of JDB0131 Benzenesulfonate Tablets in Patients With Drug-sensitive Pulmonary Tuberculosis
Official title: A Randomized, Open, Multicenter, Phase IIa Clinical Study on the Early Bactericidal Activity, Safety, Tolerance and Pharmacokinetics of JDB0131 Benzenesulfonate Tablets in Drug Sensitive Pulmonary Tuberculosis Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Drug-resistant Tuberculosis
Lead sponsor: Beijing Chest Hospital
Sponsor class: OTHER
Collaborators: name: West China Hospital
name: Wuhan Pulmonary Hospital
First posted: 2024-01-25
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: EBA
timeFrame: he change of TB bacterium burden in sputum from Day 0 to Day 2 and/or Day 14
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: average of 6 month
measure: Percentage of Participants With Immediately Reportable Events (IREs)
timeFrame: average of 6 month
measure: ECG
timeFrame: an average of 6 month
measure: Safe tolerance
timeFrame: through study completion, an average of 6 month
measure: Safe tolerance
timeFrame: through study completion, an average of 6 month
measure: Tmax
timeFrame: Day 0 to Day 21
measure: Cmax
timeFrame: Day 0 to Day 21
measure: AUC0-24h
timeFrame: Day 0 to Day 21
measure: T Tss,max
timeFrame: Day 0 to Day 21
measure: Css,max
timeFrame: Day 0 to Day 21
measure: Css,min
timeFrame: Day 0 to Day 21
measure: Css,avg
timeFrame: Day 0 to Day 21
measure: t1/2,ss
timeFrame: Day 0 to Day 21
measure: AUC0-12,ss
timeFrame: Day 0 to Day 21
measure: AUC0-t,ss
timeFrame: Day 0 to Day 21
measure: AUC0-∞,ss
timeFrame: Day 0 to Day 21
measure: Vd,ss
timeFrame: Day 0 to Day 21
measure: CL,ss
timeFrame: Day 0 to Day 21
measure: Rac（Cmax）
timeFrame: Day 0 to Day 21
measure: Rac（AUC）
timeFrame: Day 0 to Day 21
measure: Fluctuation coefficient
timeFrame: Day 0 to Day 21
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Wuhan Chest Hospital (Wuhan Institute For Tuberculosis Control)
state: Hubei
city: Chendu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
References: