A Non-Inferiority, Randomized, Blind Laboratory Analysis, Controlled Trial Comparing One and Two Doses Regimes of Oxfendazole Versus a Two Dose Regime of Triclabendazole to Treat Chronic Fascioliasis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 336
- 主要终点
- Egg reduction rate day 7
研究概览
简要总结
Randomized clinical trial comparing the efficacy and safety of oxfendazole at 20 mg/kg per dose in one and two dose regimens with a two-dose regimen of triclabendazole at 10 mg/kg in an endemic region of the highlands of Peru. Adults with fascioliasis in rural communities will be screened for inclusion and exclusion criteria and a total of 336 subjects (112 per study arm) with chronic Fasciola infection will be enrolled and assigned randomly to the study arms in a 1:1:1 ratio. The primary efficacy (cure and egg reduction) endpoints will be assessed on day 7 and 30 post treatment. The secondary safety endpoint visits will be performed in days 0, 3, 7 and 30 post-treatment and Population Pharmacokinetics (PK) modeling studies will be performed in the first 24 hours after the first dose of oxfendazole.
详细描述
Quality Control and Quality Assurance Following a written Data Safety and Monitoring Board (DSMB)-accepted site quality management plan, the participating site and the subcontractors will be responsible for conducting routine quality assurance and quality control activities to internally monitor study progress and protocol compliance. The site principal investigator will provide direct access to all study-related sites, source data/data collection forms, and reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and regulatory authorities.
The site principal investigator will ensure all study personnel are appropriately trained and applicable documentations are maintained on site. The study principal investigator is the person primarily responsible for assuring compliance. The study principal investigator will regularly review the study progress with team members and conduct periodic audits to ensure that informed consent has been obtained and documented. The principal investigator will review the team operations and progress to ensure that study records are up to date, complete, and kept in a secure place accessible only to appropriate study personnel.
Data Handling and Record Keeping The investigator is responsible to ensure the accuracy, completeness, legibility, and timeliness of the data reported. All source documents will be completed in a neat, legible manner to ensure accurate interpretation of data.
Data collection forms will be derived from the Case Report Forms (CRF) and provided to the study site to record and maintain the data for each subject enrolled in the study. Data reported in the CRF derived from source documents will be consistent with the source documents or the discrepancies will be explained.
The data collection is the responsibility of the clinical trial staff at the site under the supervision of the site principal investigator. The investigator will maintain complete and accurate documentation for the trial. All source documents and laboratory reports will be reviewed by the clinical team and data entry staff to ensure the accuracy and completeness. Adverse Events (AE) will be graded, assessed for severity and causality, and reviewed by the site principal investigator or a designee.
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
- Double (Care Provider, Outcomes Assessor)
盲法说明
The laboratory personnel processing the stool microscopy tests will be blinded to the treatment assignment. Thus, the intervention will be blinded to the assessors of the primary endpoint.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects eighteen years or older with positive stool microscopy and/or egg counts confirmed by qualitative and/or quantitative stool microscopy performed within the past 14 days.
- •Subjects capable of understanding the informed consent process and providing written informed consent.
- •Willingness to give informed consent.
排除标准
- •Subjects reporting previous treatment for fascioliasis
- •Subjects with a stool egg count > 300 eggs/g in stool samples
- •Women with a positive urine pregnancy test or planning to become pregnant
- •Women that are nursing
- •Alanine aminotransferase (ALT) ≥ 3 or Aspartate aminotransferase (AST) ≥ 3 times above the upper limit of normal within 14 days before enrollment.
- •Subjects with active cerebral cysticercosis determined by serology and imaging studies
- •Subjects with known liver disease, liver cirrhosis, or end stage renal disease
- •Subjects with known allergy or AEs to benzimidazole drugs
- •Subjects taking carbamazepine, phenobarbital, phenytoin, or other medication known to decrease the serum concentrations of benzimidazoles.
- •Women unable or unwilling to use an acceptable birth control method.
- •Male volunteers who are unwilling to ensure pregnancy prevention in their partner.
- •Volunteers with a previously recorded electrocardiogram showing heart-rate corrected (QTc) prolongation, or who are taking medications associates with heart-rate corrected (QTc) prolongation, such as selective serotonin reuptake inhibitors, quinolones, or macrolides.
- •Volunteers with acute fascioliasis.
- •Volunteers who fail to demonstrate adequate understanding of the study after three attempts.
研究组 & 干预措施
Triclabendazole
Triclabendazole 250 mg tablets at 10 mg/kg of body weight per dose in two oral doses separated 24 hours each administered with a lipid containing meal under direct observation.
干预措施: Triclabendazole (Drug)
Oxfendazole two doses
Oxfendazole 100 mg capsules at 20 mg/kg of body weight per dose in two oral doses separated 24 hours each administered with a lipid containing meal under direct observation.
干预措施: Oxfendazole (Drug)
Oxfendazole single dose
Oxfendazole 100 mg capsules at 20 mg/kg of body weight as a single oral dose administered with a lipid containing meal under direct observation.
干预措施: Oxfendazole (Drug)
结局指标
主要结局
Egg reduction rate day 7
时间窗: At day 7 post-treatment.
The egg reduction rate will be expressed as a percentage calculated comparing the visit egg count to the baseline egg count
Parasitological cure rate of chronic fascioliasis
时间窗: At day 30 post-treatment.
The cure rate will be expressed as the proportion of subjects in each arm with negative tests for Fasciola eggs.
Egg reduction rate day 30
时间窗: At day 30 post-treatment.
The egg reduction rate will be expressed as a percentage calculated comparing the visit egg count to the baseline egg count
次要结局
- Safety information on day 0(Day 0 after first dose of study medication.)
- Safety information on day 30(Day 30 after first dose of study medication.)
- Population pharmacokinetics model constructs fenbendazole(Day 0)
- Safety information on day 3(Day 3 after first dose of study medication.)
- Safety information on day 7(Day 7 after first dose of study medication.)
- Population pharmacokinetics model constructs for oxfendazole(Day 0)
- Laboratory safety information day 30(Day 30 after first dose of study medication)
- Laboratory safety information day 7(Day 7 after first dose of study medication)
- Population pharmacokinetics model constructs for oxfendazole sulfone(Day 0)