Safety and Pharmacokinetics of a Novel Niclosamide Solution in Combination With Camostat
- Registration Number
- NCT04644705
- Lead Sponsor
- Charité Research Organisation GmbH
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
- 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
- Significant illness
- pregnant or lactating women
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Part A: placebo to niclosamide Placebo 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) Part C: placebo to niclosamide and camostat Placebo 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. Part A: verum niclosamide 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) Part B: verum as solution (niclosamide) 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. Part B: verum as chewing tablet (niclosamide) 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. Part C: verum (niclosamide and camostat) Niclosamide 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.
- Primary Outcome Measures
Name Time Method Maximum plasma concentration of niclosamide (µg/ml) 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] from predose until 24 hours after intervention Measurement will start at Day 1
Treatment emergent number of Adverse Events up to 14 days Assessment of severity of an AE will be based on CTCAE Version 5.0
- Secondary Outcome Measures
Name Time Method 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 Measurement will start at Day 1 after a standard high fat breakfast
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 Measurement will start at Day 1 after a standard high fat breakfast
Trial Locations
- Locations (1)
Charité Research Organisation GmbH
🇩🇪Berlin, Germany