Pharmacokinetic Study of Minocycline in Patients With Pulmonary Nontuberculous Mycobacterial Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.
研究概览
简要总结
Antimycobacterial treatment of M. avium complex pulmonary disease (MAC-PD) has suboptimal cure rates and is challenging due to frequent adverse drug reactions and drug-drug interactions. Hence, there is an urgent need for improved treatment regimens with effective and tolerable antibiotics.
Minocycline is a well-tolerated, orally administered tetracycline-type antibiotic with in vitro activity against MAC, but pharmacokinetic data in the target population is lacking. Moreover, rifampicin, a strong inducer of cytochrome P450 enzymes involved in drug metabolism and of various drug transporters, is part of the current first-line MAC-PD treatment regimen and has a substantial interaction with doxycycline, a related tetracycline.
Pharmacokinetic data in the target population will allow us to propose an appropriate dose of minocycline when co-administered with or without rifampicin
Mino-PK is an open label, one-arm, two-period, fixed-order pharmacokinetic study that will assess exposure to minocycline in MAC-PD patients with and without concurrent use of rifampicin. Subjects will receive two 5-day dosing periods of minocycline; the first without and second with concurrent use of rifampicin. Minocycline plasma concentrations will be determined after both dosing periods.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •2020 guideline (ATS/ERS/ESCMID/IDSA) diagnostic criteria for nontuberculous mycobacterial pulmonary disease are met, i.e. the patient is symptomatic, has nodules, bronchiectasis or fibro-cavitary lesions seen on (HR)CT scan of the lungs and ≥2 positive sputum cultures or one positive bronchoalveolar lavage culture of the same M. avium complex species.
- •At least one of the positive cultures must be done in the last 4 months before inclusion.
- •The subject is eligible to start the guideline-recommended rifampicin-based regimen according to the treating physician.
- •Age ≥ 18 years.
- •Signed and dated patient informed consent.
排除标准
- •A relevant medical history or current condition that might interfere with drug absorption, distribution, metabolism or excretion (i.e. chronic gastro-intestinal disease, renal or hepatic disease).
- •Diagnosed with cystic fibrosis (as this may affect the pharmacokinetics of drugs).
- •Pregnant or breastfeeding (contra-indications for minocycline) or inadequate contraceptive measures (in view of the administration of rifampicin which interacts with oral contraceptive drugs, adequate contraceptive measures are abstinence from sexual activities and barrier methods).
- •Use of drugs that cause a relevant drug interaction with minocycline, i.e. oral magnesium, , bismuth, aluminium, calcium, zinc or iron containing formulations, antacid drugs and drugs besides rifampicin that are strong inducers of metabolic enzymes, including barbiturates, carbamazepin and phenytoin (as judged by the investigators).
- •ALAT > 3 times the upper limit of normal (normal <45 U/l).
- •ASAT > 3 times the upper limit of normal (normal <35 U/l).
- •An abnormal serum creatinine level (defined as a level that is higher than the upper limit of normal, i.e. >110 umol/l).
- •Active alcohol abuse.
- •Hypersensitivity to minocycline or to other tetracycline antibiotics.
结局指标
主要结局
Pharmacokinetic parameters of minocycline in MAC-PD patients without concurrent use of rifampicin.
时间窗: Day 5 of the first minocycline dosing period
The area under the curve (AUC0-24h)
次要结局
- Pharmacokinetic parameters of rifampicin in MAC-PD patients(Day 5 of the second minocycline dosing period)
- Adverse Events(Through study completion, an average of 6 weeks)
- Pharmacokinetic parameters of minocycline in MAC-PD patients with concurrent use of rifampicin.(Day 5 of the second minocycline dosing period)