Tuberculosis MedDRA version: 20.0 Level: PT Classification code 10044755 Term: Tuberculosis System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Pyrazinamide
Pharmaceutical Form: Tablet
INN or Proposed INN: PYRAZINAMIDE
CAS Number: 98-96-4
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration num
Sponsors
Region Östergötland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patient> 18 years 2) Confirmed active lung TB by positive culture or positive PCR for the M.tuberculosis complex. 3) Planned to start on active TB treatment (first line) but not yet started treatment. 4) HIV negative 5) BMI> 17 6) Have given written consent. 7) Fertile women should use adequate non-hormonal contraceptives such as a condom and submit to a serum negative pregnancy test if the woman is not postmenopausal. Female patients are not considered fertile if they are post-menopausal, without menstruation for the last 12 months or surgically sterile (bilateral oophorectomy, hysterectomy, tubal ligation 12 months before study start). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1) The research person is not able to give informed consent or is considered so affected by his illness that he or she is unable to understand the study information. 2) Other concurrent infectious disease requiring active treatment. 3) Known hypersensitivity to rifamycin, isoniazid, pyrazinamide, etambutol hydrochloride and / or to any of the excipients listed in section Summary of Product Characteristics or previous serious adverse reaction to RIF, INH, PZA or EMB. 4) Contraindications according to the summary of product characteristics of RIF, INH, PZA or EMB: • Known hypersensitivity according to exclusion criterion 3 above and severe renal failure (creatinine clearance / = 15 mg prednisolone or equivalent cortisone dose) 12) Heart failure fulfilling NYHA Class III or IV 13) Renal failure with estimated GFR 62 mmol /mol for type I diabetes and HbA1c> 52 mmol /mol for type II diabetes. 15) Known liver disease including hepatitis and elevated liver transaminases (transaminases> x1.5 of the reference value). 16) Alcohol and / or drug dependence based on patient history. 17) A research person who the investigator after discussing with the study leader, forother reasons than the above, is deemed not suitable for inclusion. 18) Weight 90 kg at inclusion 19) Patient participated in a clinical trial within 30 days prior to inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary purpose is to investigate the pharmacokinetics of PZA (given for 8 weeks) in a 4-month treatment with higher doses of RIF (35 mg/kg) and PZA (40 mg/kg) and standard treatment of INH (5 mg / kg) and EMB (15-20 mg / kg) compared to standard treatment (RIF 10 mg / kg and PZA 20-30 mg / kg as well as INH and EMB in the above standard doses).;Secondary Objective: 1 The inter-individual variability of drug exposure (AUC0-24h) after the first dose and after two weeks of treatment for high-dose RIF. 2. Cmax for highdose RIF/PZA 3. Comparisons of drug exposure for high-dose PZA and high-dose RIF between day 1 and day 14 on individual level. 4 Is it possible by this high-dose regimen to receive higher drug exposure of PZA than previously proposed thresholds AUC0-24h> 363 mg.h / L and Cmax> 35 mg/L for> 90% of the patients? 5 Characterization of primary PK parameters for high-dose PZA/RIF. 6. The incidence and severity of adverse events (AEs) and SAEs 7. Drug exposure in relation to the bacterial susceptibility level in intervention group and control group with correlation to PK/PD. 8. Description of TBscore during the first 2 treatment months. 9. suPAR during the first 2 months of treatment ;Primary end point(s): The primary variable is the area under concentration and time curve (AUC0-24h) for high dose PZA, in a combination regimen with high dose RIF together with standard doses of INH and EMB, at day 1 after the first dose and at treatment week 2.;Timepoint(s) of evaluation of this end point: Day 1 and day 14: AUC measured under 24 hours. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. AUC0-24h for RIF. 2. Cmax for RIF and PZA 3. Primary pharmacokinetic parameters for RIF and PZA 4. Drug exposure in relationship to the susceptibility level of the bacteria (Cmax/MIC and AUC0-24h/MIC). 5. AE and SAE 6. Correlation between TTP and PCR reactivity (Ct value) 7. Description of TB score 8. Description of suPar;Timepoint(s) of evaluation of this end point: Point 1,2 and 3: are measured under day 1 and day 14. Point 5: From treatment starts until 4 months for the intervention group and 6 months for the control group. Point 4 and 6: During the first two weeks. Point 7 and 8: during the first two months of treatment. | — |
Countries
Sweden
Contacts
Public ContactKatarina Niward
Region Östergötland
Outcome results
None listed