A 3-part Study to Investigate the Safety and Pharmacokinetics of a Novel Niclosamide Solution as a Treatment Option for COVID-19 in Combination With Camostat
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Maximum plasma concentration of niclosamide (µg/ml)
研究概览
简要总结
Niclosamide is a well-established substance that is a promising candidate for a repurposing approach to treat COVID-19. Niclosamide is currently marketed as a chewing tablet for the treatment of intestinal worm infections. The marketed formulation is optimized for minimal drug substance absorption. A niclosamide solution has been developed that is expected to release the drug substance more readily and more reproducibly.
Camostat is approved for oral treatment of chronic pancreatitis and reflux oesophagitis in Japan. Camostat has been shown to effectively block viral replication in a SARS-CoV-2 animal model. Since the mechanisms of actions are different, it was hypothesized that a combination of both substances might have an additive or even synergistic effect in the treatment of COVID-19 patients.
This 3-part study is designed to investigate (1) safety and pharmacokinetics of single ascending doses of the new niclosamide solution after fasted and fed conditions, (2) the relative bioavailability of the niclosamide solution compared to the chewing tablet, and (3) safety and pharmacokinetics of the combination of niclosamide solution and camostat after multiple doses in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This three part study has double-blinded (placebo-controlled) and open-label parts.
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subjects in good health as determined by past medical history
- •physical examination, vital signs and safety lab at screening
- •between 18 to 45 years of age
排除标准
- •Significant illness
- •pregnant or lactating women
研究组 & 干预措施
Part A: verum niclosamide
The SAD cohorts are planned as follows:
Cohort A1: 200 mg (fasted conditions) Cohort A2: 600 mg (fasted conditions) Cohort A3: 1600 mg (fasted and fed conditions)
干预措施: Niclosamide (Drug)
Part A: placebo to niclosamide
The SAD cohorts are planned as follows:
Cohort A1: placebo to niclosamide 200 mg (fasted conditions) Cohort A2: placebo to niclosamide 600 mg (fasted conditions) Cohort A3: placebo to niclosamide 1600 mg (fasted and fed conditions)
干预措施: Placebo (Drug)
Part B: verum as solution (niclosamide)
Two different crossover designs are chosen. Both are randomized, open-label, two-sequence, two periods crossover designs comparing the new niclosamide solution with the marketed chewing tablets. Planned doses are 1600 mg once daily (oral solution), 2000 mg once daily (chewing tablets) and 500 mg three times daily of both dosage forms.
干预措施: Niclosamide (Drug)
Part B: verum as chewing tablet (niclosamide)
Two different crossover designs are chosen. Both are randomized, open-label, two-sequence, two periods crossover designs comparing the new niclosamide solution with the marketed chewing tablets. Planned doses are 1600 mg once daily (oral solution), 2000 mg once daily (chewing tablets) and 500 mg three times daily of both dosage forms.
干预措施: Niclosamide (Drug)
Part C: verum (niclosamide and camostat)
Subjects will receive the combination of niclosamide solution (planned 500 mg three times daily) + camostat (600 mg three times daily) or placebo over a treatment period of 7 days. The dose of the niclosamide solution depends on the safety and pharmacokinetic results of Part A and B but will not exceed 500 mg three times daily.
干预措施: Niclosamide (Drug)
Part C: placebo to niclosamide and camostat
Subjects will receive the combination of niclosamide solution (planned 500 mg three times daily) + camostat (600 mg three times daily) or placebo over a treatment period of 7 days. The dose of the niclosamide solution depends on the safety and pharmacokinetic results of Part A and B but will not exceed 500 mg three times daily.
干预措施: Placebo (Drug)
结局指标
主要结局
Maximum plasma concentration of niclosamide (µg/ml)
时间窗: from predose until 24 hours after intervention
Measurement will start at Day 1
Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide(AUC0-last) of niclosamide [µg/ml*h]
时间窗: from predose until 24 hours after intervention
Measurement will start at Day 1
Treatment emergent number of Adverse Events
时间窗: up to 14 days
Assessment of severity of an AE will be based on CTCAE Version 5.0
次要结局
- Area Under the Plasma Concentration Time Curve between two dosing intervals (AUC tau ss) of niclosamide [µg/ml*h] at steady state after multiple dosing(from predose until Day 9)
- Maximum plasma concentration of niclosamide (µg/ml) at steady state after multiple dosing(from predose until Day 9)
- Food effect on maximum plasma concentration of niclosamide (µg/ml)(from predose until 24 hours after intervention)
- Food effect on Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide (AUC0-last) [µg/ml*h](from predose until 24 hours after intervention)