A Randomized, Double-Blind, Active Drug Controlled Study to Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Liver Injury in Subjects With Pulmonary Tuberculosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 557
- 试验地点
- 18
- 主要终点
- ALT change from baseline to the 8 weeks of study treatment
研究概览
简要总结
Assess the Efficacy of HUEXC030 as Add-on Excipient to Eradicate Anti-Tuberculosis Drugs Induced Hepatic Injury ( ATDH ) in Subjects with Pulmonary Tuberculosis
详细描述
The study drug is Isoniazid formulated with HUEXC030 as excipient for eradicating ATDH, whereas the reference control is Isoniazid formulated with inactive excipient. Subjects who fulfill all the entry criteria and have written informed consent will be enrolled to the study. Eligible subjects will be randomized in a 1:1 ratio to receive study drug or reference control drug. Subjects will be genotyped according to a selected panel of single nucleotide polymorphisms (SNPs) and categorized into high risk or low risk groups for occurring ATDH via a specific haplotype consists of CYP2E1 and NAT2 SNPs. Based on an extensive study result during 2007 to 2011,the estimated frequency for patients bearing high risk genotypes in Taiwanese population is around 25%. Approximately 352 subjects will be enrolled for genotype screening in order to recruit 88 high risk subjects for each of 44 subjects in the intervention and control arms.
Subjects who are stratified as high risk groups will be administered the test drug or reference control drugs oral daily for 6 months or until treatment completion, i.e. bacteriologically confirmed negative of active M. tuberculosis. Subjects who are of low risk genotype will be removed from study after 8 weeks of study treatment, then return to conventional TB medication under the care of their investigator for at least one follow-up visit at 4 weeks after the End of Study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Have alcoholic liver disease or habitual alcohol consumption > 30 g/day for more than one year
- •Previously diagnosed of:
- •i. extra-pulmonary TB without concomitant lung invasion ii. HIV iii. liver malignancy iv. liver cirrhosis v. any other systemic diseases that may cause liver dysfunction
- •Documented history of serious allergic reaction or resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, sugar alcohols or any structurally related compounds
- •Subjects who will be using the following therapies after TB treatment starts:
- •i. antiretroviral agents ii. oral corticosteroids
- •Subjects are pregnant or lactating
- •Subjects with child-bearing potential who are not committed to take reliable contraception during the participation of the study and at least 4 weeks after the end of the study treatment
- •Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial
研究组 & 干预措施
Isoniazid with HUEXC030 and RZE
Subjects who are genotyped as high risk group will be receiving 2 months of intensive treatment comprised of 4 drugs (Isoniazid with HUEXC030 [H], rifampin [R], pyrazinamide [Z] and ethambutol [E]), followed by 4 months of continual chemotherapy consist of Isoniazid, Rifampin (2HRZE/4HR regimen). Subjects who are of low risk genotype will be removed from study after 8 weeks of study treatment, then return to conventional TB medication at least one follow-up visit at 4 weeks after the end of study treatment visit.
Dosage is as below:
Isoniazid with Isoniazid(H):300mg/600mg daily, rifampin [R]: 450~600mg daily, pyrazinamide [Z]; 1000~2000mg daily and ethambutol [E]: 800-1600mg daily)
干预措施: Isoniazid with HUEXC030 and RZE (Drug)
Isoniazid
Subjects who are genotyped as high risk group will be receiving 2 months of intensive treatment comprised of 4 drugs (Isoniazid [H], rifampin [R], pyrazinamide [Z] and ethambutol [E]), followed by 4 months of continual chemotherapy consist of Isoniazid, Rifampin (2HRZE/4HR regimen). Subjects who are of low risk genotype will be removed from study after 8 weeks of study treatment, then return to conventional TB medication at least one follow-up visit at 4 weeks after the end of study treatment visit.
Dosage is as below:
Isoniazid (H):300mg daily, rifampin [R]: 450~600mg daily, pyrazinamide [Z]; 1000~2000mg daily and ethambutol [E]: 800-1600mg daily)
干预措施: HRZE (Drug)
结局指标
主要结局
ALT change from baseline to the 8 weeks of study treatment
时间窗: 8 weeks
The primary efficacy endpoint is the time-interval weighted area under the curve (AUC) of change from baseline in serum ALT, primarily in patients with high risk genotypes. The area under ALT change curve was estimated using the linear trapezoidal rule. The AUC was a measure of cumulative ALT differences from baseline to the 8 weeks of double-blind treatment period.
次要结局
- Percentage of patients cured by the end of treatment(26 weeks)
- The overall reduced incidence of ATDH in subjects treated with investigational drugs(26 weeks)
- The lowering average level of liver function tests(26 weeks)
- Incidence of ATDH in high risk genotype subjects treated with investigational drugs(26 weeks)