An Open-Label Phase 2 Trial to Evaluate the Male Reproductive Safety of a 6-Month Combination Treatment for Pulmonary Tuberculosis (TB) of Bedaquiline Plus Pretomanid Plus Moxifloxacin Plus Pyrazinamide (BPaMZ) in Adult Male Participants With Drug Resistant Pulmonary TB
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 4
- 主要终点
- Change Form Baseline Total Sperm Count
研究概览
简要总结
Pretomanid is being used in an antimicrobial combination regimen(s) to treat patients with pulmonary tuberculosis (TB). The primary purpose of the Male Reproductive Safety - "BPaMZ/SEM"- clinical study is to evaluate the potential effect of pretomanid on human testicular function whilst being used in a 26 weeks antimicrobial combination regimen consisting of bedaquiline (B) plus pretomanid (Pa) plus moxifloxacin (M) and pyrazinamide (Z) (BPaMZ).
详细描述
The primary objective of this study is to assess the male reproductive safety of pretomanid in the regimen (BPaMZ) of bedaquiline 200mg (200mg daily for 8 weeks then 100 mg daily for 18 weeks), together with pretomanid 200 mg (1x daily) + moxifloxacin 400 mg (1x daily) + pyrazinamide 1500 mg (1 x daily) for 26 weeks in participants with drug-resistant pulmonary tuberculosis (DR-TB).
The secondary objective of the study is to evaluate the tuberculosis (TB) treatment efficacy, safety and tolerability after 26 weeks of active treatment for TB and follow up until 52 weeks after end of the above-described treatment regimen in participants with DR-TB.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Understands study procedures and voluntarily provides written informed consent prior to the start of any study-specific procedures.
- •Male gender 18 years or over
- •Body weight (in light clothing and no shoes) ≥ 45kg.
- •A positive molecular test for tuberculosis in sputum either at screening or within one month prior to enrolment.
- •Disease Characteristics:
- •Participants must have been diagnosed with TB prior to or at screening
- •Participants' TB should be resistant to rifampicin and/or isoniazid, and susceptible to fluoroquinolones by rapid sputum-based tests.
- •Participants who have had previous treatment for DR-TB for more than 3 months at start of screening should be discussed with the medical monitor.
- •A chest x-ray, within 26 weeks prior to or at the screening visit, which in the opinion of the Investigator is compatible with pulmonary TB
- •Exclusion criteria:
- •Resistant to fluoroquinolones by rapid molecular test
- •History of male infertility or vasectomy
- •Unable to produce semen sample
- •Evidence at screening of azoospermia
- •Known erectile dysfunction that would prevent ejaculation.
- •Historical or active disease process of the male reproductive tract that would compromise sperm production. e.g. tuberculous epididymitis.
- •History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
- •For HIV infected participants any of the following:
- •CD4+ count <100 cells/μL
- •Received intravenous antifungal medication within the last 90 days
- •Participants with newly diagnosed tuberculosis and HIV that require initiation of appropriate HIV therapy before participants has received at least 2 weeks of an antituberculosis regimen.
- •Received pretomanid and/or delamanid to treat TB
- •Known chronic hepatitis B or C
- •For HIV infected participants:
- •The following antiretroviral therapy (ART) should not be used:
- •Triple NRTI regimen is not considered optimal for HIV treatment (poor efficacy)
- •Participants with the following toxicities at screening as defined by the enhanced Division of Microbiology and Infectious Disease (DMID) adult toxicity table (Draft November 2007) where applicable:
- •Platelets <75,000/mm3
- •Creatinine >1.5 times upper limit of normal (ULN)
- •eGFR ≤ 60 mL/min
- •Haemoglobin <8.0 g/dL
- •Serum potassium less than the lower limit of normal for the laboratory. This may be repeated once
- •≥3.0 x ULN to be excluded
- •results between 1.5 x ULN and 3 x ULN must be discussed with and approved by the Sponsor Medical Monitor
- •≥3.0 x ULN to be excluded
- •greater than ULN must be discussed with and approved by the Sponsor Medical Monitor
- •≥3.0 x ULN to be excluded
- •2.0 - <3.0 x ULN must be discussed with and approved by the Sponsor Medical Monitor
- •Total bilirubin:
- •>1.5 x ULN to be excluded
- •Greater than ULN must be discussed with and approved by the Sponsor Medical Monitor
- •Direct bilirubin:
- •greater than 1x ULN to be excluded
- •Positive hepatitis B surface Ag, or hepatitis C antibody
排除标准
- 未提供
研究组 & 干预措施
Study Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
干预措施: Pretomanid (Drug)
Study Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
干预措施: Bedaquiline (Drug)
Study Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
干预措施: moxifloxacin (Drug)
Study Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
干预措施: pyrazinamide (Drug)
结局指标
主要结局
Change Form Baseline Total Sperm Count
时间窗: Week 26
Change from baseline in total sperm number at 26 weeks of therapy. Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.
次要结局
- Change From Baseline in Total Sperm Count at 12 Weeks(Baseline to Week 12)
- Change From Baseline Total Sperm Count at 44 Weeks(Baseline through 44 weeks)
- Luteinizing Hormone (LH)(Baseline to Week 78)
- FSH(Baseline to week 78)
- Testosterone(Baseline to 78 weeks)
- Inhibin B(Baseline to 78 weeks)