TBTC Study 27/28 PK: Pharmacokinetic Issues in the Use of Moxifloxacin for Treatment of Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 8
- 主要终点
- Compare in healthy volunteers the pharmacokinetics of moxifloxacin alone versus moxifloxacin administered with rifampin.
研究概览
简要总结
This substudy of TBTC Studies 27 and 28 compares 1) the pharmacokinetics of moxifloxacin alone versus moxifloxacin administered with rifampin in healthy volunteers and 2) the pharmacokinetics of moxifloxacin among patients with tuberculosis being treated with multidrug therapy (isoniazid or ethambutol, rifampin, and pyrazinamide) to those of healthy volunteers receiving moxifloxacin plus rifampin. It also evaluates the association between polymorphisms of MDR1 genotype (P-glycoprotein) and rifampin pharmacokinetic parameters, the effect of polymorphisms of MDR1 genotype and/or rifampin pharmacokinetics on isoniazid pharmacokinetic parameters adjusted for N-acetyltransferase genotype (NAT2), and determines by multivariate regression analyses the associations between moxifloxacin or rifampin pharmacokinetic parameters and markers of tuberculosis disease severity including the covariates of two-month culture positivity, cavitary lung disease, Body Mass Index, weight, duration of study treatment prior to PK, co-morbidities and C-reactive protein. Healthy volunteers and TB patients receive frequent scheduled blood draws during a 24 hour period after ingesting a dose of TB drugs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Healthy Volunteers:
- •Provision of informed consent for the study.
- •Age > 18 years.
- •Willingness to be available for 2 weeks of DOT.
- •Willingness to be admitted to a GCRC or hospital on two occasions.
- •Women of child-bearing potential must agree to practice an adequate method of birth control. Barrier methods of contraception or abstinence from sexual activity are satisfactory methods.
- •Willingness to have HIV testing done if documented results are not available. (A prior negative result must be obtained within one year and consists of a negative HIV ELISA. A positive result must be both a positive HIV ELISA and Western Blot, or a plasma HIV PCR RNA level greater than 5000 copies/ml).
- •Laboratory screening (if not already available) within 30 days of the first PK admission:
- •Serum potassium within normal limits
- •Hematocrit > 35%
- •Absolute neutrophil count > 1000 /mm3
- •AST < 3 times the upper limit of normal
- •Bilirubin < 2 times the upper limit of normal
- •Creatinine < 2 times the upper limit of normal
- •Eligible and enrolled for medical health care sponsored by the United States federal government (such as the Veterans Administration enrollment Priority 1 through 7, VHA Directive 2003-003).
- •For Patients with Tuberculosis Enrolled in TBTC Study 27 or Study 28:
- •Any patient enrolled in TBTC Study 27 or Study 28 receiving a daily (5-7 days per week) regimen.
- •Provision of informed consent for the study.
- •Willingness to be admitted to a GCRC or hospital on one occasion.
排除标准
- •For Healthy Volunteers:
- •Karnofsky score less than 90
- •Pregnancy or breast-feeding. (A negative pregnancy test is required for women of childbearing potential within 14 days before the first dose of moxifloxacin.)
- •Known allergy to any fluoroquinolone or rifamycin antibiotic
- •Current or planned therapy during the study with drugs having unacceptable interactions with rifampin
- •History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during period of administration of moxifloxacin and for one week after treatment
- •For Patients with Tuberculosis Enrolled in TBTC Study 27 or Study 28:
- •Severe anemia as defined by a hematocrit less than 25% (most recent value, measured within 30 days of the PK study).
- •History of severe liver disease classified as Child Pugh Class C.
研究组 & 干预措施
Moxifloxacin
Moxifloxacin 400 mg po qd given 5 of 7 days per week
干预措施: Moxifloxacin (Drug)
Isoniazid
Isoniazid 300 mg po qd given 5/7 days per week
干预措施: Isoniazid (Drug)
结局指标
主要结局
Compare in healthy volunteers the pharmacokinetics of moxifloxacin alone versus moxifloxacin administered with rifampin.
时间窗: study period
Compare the pharmacokinetics of moxifloxacin among patients with tuberculosis being treated with multidrug therapy (isoniazid or ethambutol, rifampin, and pyrazinamide) to those of healthy volunteers receiving moxifloxacin plus rifampin.
时间窗: study period
次要结局
- Determine the association between polymorphisms of MDR1 genotype (P-glycoprotein) and rifampin PK parameters.(study period)
- Determine variation of moxifloxacin pharmacokinetics (PK) among patients with pulmonary TB during treatment.(study period)
- Compare serum concentrations of isoniazid rifampin and pyrazinamide among patients being treated with moxifloxacin versus patients being treated with ethambutol as the fourth drug in multidrug treatment.(study period)
- Compare serum concentrations of rifampin, pyrazinamide and ethambutol among patients being treated with moxifloxacin versus patients being treated with isoniazid as the fourth drug(study period)
- Determine the effect of polymorphisms of MDR1 genotype and/or rifampin PK on isoniazid PK parameters adjusted for N-acetyltransferase genotype (NAT2).(study period)
- Determine the effects of polymorphisms of MDR1 and UGT genotypes on moxifloxacin PK parameters.(study period)
- Determine by multivariate regression analyses the associations between moxifloxacin or rifampin PK parameters and markers of disease severity.(study period)