NIC-002: Safety and Pharmacokinetics of a Novel Niclosamide Solution in Combination With Camostat
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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) |
Drug: Niclosamide
Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
|
| Placebo Comparator: 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) |
Drug: Placebo
placebo to the interventional drug
|
| Active Comparator: 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. |
Drug: Niclosamide
Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
|
| Active Comparator: 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. |
Drug: Niclosamide
Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
|
| Active Comparator: 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. |
Drug: Niclosamide
Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat
|
| Placebo Comparator: 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. |
Drug: Placebo
placebo to the interventional drug
|
Outcome Measures
Primary Outcome Measures
- Treatment emergent number of Adverse Events [up to 14 days]
Assessment of severity of an AE will be based on CTCAE Version 5.0
- 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
Secondary Outcome Measures
- 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
- Maximum plasma concentration of niclosamide (µg/ml) at steady state after multiple dosing [from predose until Day 9]
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
Significant illness
-
pregnant or lactating women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Charité Research Organisation GmbH | Berlin | Germany | 10117 |
Sponsors and Collaborators
- Charité Research Organisation GmbH
- Bayer
Investigators
- Principal Investigator: Maximilian Posch, Dr. med., Charité Research Organisation GmbH
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 201767