Safety and Pharmacokinetics of a Novel Niclosamide Solution in Combination With Camostat

NCT04644705 | Completed Phase 1

• 1 other identifier: 201767
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Treatment emergent number of Adverse Events

  Assessment of severity of an AE will be based on CTCAE Version 5.0

  up to 14 days

• Maximum plasma concentration of niclosamide (µg/ml)

  Measurement will start at Day 1

  from predose until 24 hours after intervention

• Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide(AUC0-last) of niclosamide [µg/ml*h]

  Measurement will start at Day 1

  from predose until 24 hours after intervention

Secondary Outcomes (4)

• 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

• 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

Study Arms (6)

Part A: verum niclosamide

ACTIVE COMPARATOR

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

Part A: placebo to niclosamide

PLACEBO COMPARATOR

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

Part B: verum as solution (niclosamide)

ACTIVE COMPARATOR

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

Part B: verum as chewing tablet (niclosamide)

ACTIVE COMPARATOR

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

Part C: verum (niclosamide and camostat)

ACTIVE COMPARATOR

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

Part C: placebo to niclosamide and camostat

PLACEBO COMPARATOR

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

Interventions

Niclosamide DRUG

Niclosamide will be applied in various dosage steps, galenic preparations and in combination with camostat

Part A: verum niclosamide; Part B: verum as chewing tablet (niclosamide); Part B: verum as solution (niclosamide); Part C: verum (niclosamide and camostat)

Placebo DRUG

placebo to the interventional drug

Part A: placebo to niclosamide; Part C: placebo to niclosamide and camostat

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Significant illness
• pregnant or lactating women

Sponsors & Collaborators

• Charité Research Organisation GmbH: lead
• Bayer: collaborator

Study Sites (1)

Charité Research Organisation GmbH

Berlin, 10117, Germany

Location

Related Publications (1)

• Walther N, Schultz-Heienbrok R, Stass H, Corman VM, Gassen NC, Muller MA, Drosten C, Witzenrath M, Lee H, Posch MG. Clinical safety and pharmacokinetics of a novel oral niclosamide formulation compared with marketed niclosamide chewing tablets in healthy volunteers: A three-part randomized, double-blind, placebo-controlled trial. PLoS One. 2025 Feb 25;20(2):e0303924. doi: 10.1371/journal.pone.0303924. eCollection 2025.

  PMID: 39999124 DERIVED

MeSH Terms

Interventions

Niclosamide

Intervention Hierarchy (Ancestors)

Salicylanilides; Anilides; Amides; Organic Chemicals; Salicylamides; Aniline Compounds; Amines

Study Officials

• Maximilian Posch, Dr. med.

  Charité Research Organisation GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This three part study has double-blinded (placebo-controlled) and open-label parts.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 2, 2020
• First Posted: November 25, 2020
• Study Start: November 2, 2020
• Primary Completion: May 3, 2021
• Study Completion: May 3, 2021
• Last Updated: November 29, 2021

Record last verified: 2021-11

Locations

DE (1)