Safety and Pharmacokinetics of a Novel Niclosamide Solution in Combination With Camostat (NIC-002)

• ClinicalTrials.gov Identifier: NCT04644705
• Recruitment Status: Recruiting
• First Posted: November 25, 2020
• Last Update Posted: November 25, 2020
• Sponsor: Charité Research Organisation GmbH
• Collaborator: Bayer
• Information provided by (Responsible Party): Charité Research Organisation GmbH

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
Healthy Volunteers	Drug: Niclosamide; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment

Intervention Model Description

Part A is a randomized, double-blinded, placebo-controlled, single ascending dose (SAD) study with 3 planned cohorts.

Part B consists of two randomized, open-label, two-sequence, two-period crossover cohorts comparing the new niclosamide solution with the marketed chewing tablets.

Part C is a randomized, double-blinded, placebo-controlled multiple dose study investigating the safety and pharmacokinetics of the combination of niclosamide solution and camostat over a treatment period of 7 days.

• Masking: Double (Participant, Investigator)
• Masking Description: This three part study has double-blinded (placebo-controlled) and open-label parts.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 2, 2020
• Estimated Primary Completion Date: May 31, 2021
• Estimated Study Completion Date: May 31, 2021

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 :

1. Treatment emergent number of Adverse Events [ Time Frame: up to 14 days ]
   Assessment of severity of an AE will be based on CTCAE Version 5.0
2. Maximum plasma concentration of niclosamide (µg/ml) [ Time Frame: from predose until 24 hours after intervention ]
   Measurement will start at Day 1
3. Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide(AUC0-last) of niclosamide [µg/ml*h] [ Time Frame: from predose until 24 hours after intervention ]
   Measurement will start at Day 1

Secondary Outcome Measures :

1. Food effect on maximum plasma concentration of niclosamide (µg/ml) [ Time Frame: from predose until 24 hours after intervention ]
   Measurement will start at Day 1 after a standard high fat breakfast
2. Food effect on Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide (AUC0-last) [µg/ml*h] [ Time Frame: from predose until 24 hours after intervention ]
   Measurement will start at Day 1 after a standard high fat breakfast
3. Maximum plasma concentration of niclosamide (µg/ml) at steady state after multiple dosing [ Time Frame: from predose until Day 9 ]
4. 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 [ Time Frame: from predose until Day 9 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts

Contact: Frank D Wagner, Prof. Dr. med.; +49 30 450 539 200; info@charite-research.org

Locations

Germany

Charité Research Organisation GmbH; Recruiting

Berlin, Germany, 10117

Contact: Maximilian Posch, Dr. med. +49 30 450 539 200 info@charite-research.org

Sponsors and Collaborators

Charité Research Organisation GmbH

Bayer

Investigators

• Principal Investigator: Maximilian Posch, Dr. med.; Charité Research Organisation GmbH

More Information

• Responsible Party: Charité Research Organisation GmbH
• ClinicalTrials.gov Identifier: NCT04644705
• Other Study ID Numbers: 201767
• First Posted: November 25, 2020
• Last Update Posted: November 25, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Niclosamide; Anticestodal Agents; Antiplatyhelmintic Agents; Anthelmintics; Antiparasitic Agents; Anti-Infective Agents; Antinematodal Agents