A Single and Multiple Ascending Dose Study of Niclosamide in Healthy Volunteers

A Randomized, Double-Blind, Single and Multiple Ascending Dose Study to Assess the Safety and Pharmacokinetics of Niclosamide in Healthy Adults

A single and multiple ascending dose study of ANA001 in healthy adults to assess the safety and pharmacokinetics

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Niclosamide; Drug: Placebo

Detailed Description

This is a Phase 1, single center, randomized, double blind, single ascending dose (SAD) and multiple ascending dose (MAD) study to assess the safety and pharmacokinetics of ANA001 in healthy adult subjects. In the single ascending dose portion of the study, subjects in 3 cohorts of 10 subjects each will be randomized to receive a single daily oral dose of ANA001 or matching placebo. In the multiple ascending dose portion of the study, subjects in 3 cohorts of 12 subjects each will be randomized to receive twice or thrice daily oral dose of ANA001 or matching placebo.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • WCCT Global Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Sign the study informed consent form
2. Man or woman, 18 to 65 years of age inclusive at the time of signing the informed consent form
3. Overtly healthy as determined by medical evaluation
4. Body mass index (BMI) within 18 to 30.0 kg/m2 (inclusive) and body weight not less than 50 kg
5. Blood pressure at Screening and Day -1 between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic.

6. A 12-lead electrocardiogram (ECG) at Screening consistent with normal cardiac conduction and function, including:

   • Sinus rhythm
   • Pulse rate between 50 and 100 beats per minute (bpm)
   • QTc interval 450 milliseconds (QT interval corrected using Fridericia correction method [QTcF])
   • QRS interval of <120 milliseconds
   • PR interval <200 milliseconds
   • Morphology consistent with healthy cardiac conduction and function
7. Non-smoker or ex-smoker for >12 months
8. If male, must agree to use contraception methods outlined for the study during the treatment period and for at least 30 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period
9. If female, is not pregnant, not breastfeeding, and meets at least one of the following conditions:

Not a woman of childbearing potential (WOCBP)

OR

A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days (one menstrual cycle) after the last dose of study treatment.

Exclusion Criteria:

1. Has a history of or current clinically significant medical illness including but not limited to, cardiac arrhythmias or other cardiac disease; hematologic disease; coagulation disorders (including any abnormal bleeding or blood dyscrasias); lipid abnormalities; significant pulmonary disease, including bronchospastic respiratory disease; diabetes mellitus; hepatic or renal insufficiency (creatinine clearance below 60 mL/min); thyroid disease; neurologic or psychiatric disease; infection; or any other illness that the Investigator considers should exclude the subject or that could interfere with the interpretation of the study results.
2. Has known allergy to niclosamide or salicylate-containing medications.
3. Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening.
4. Clinically significant abnormal physical examination, vital signs or 12 lead ECG at screening.
5. Has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV; has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
6. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria within 5 years before screening or positive test result(s) for alcohol and/or drugs of abuse at screening and admission
7. Has received an investigational drug or used an invasive investigational medical device within 1 month or within a period less than 10 times the drug's half-life, whichever is longer, before Day 1.
8. Has preplanned surgery or procedures that would interfere with the conduct of the study
9. Is an employee of the Investigator or study site, with direct involvement in the proposed study or other studies under the direction of that Investigator or study site, as well as family members of the employees or the Investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD Cohort 1: ANA001 1000 mg po; Subjects will receive a 1000 mg single oral dose of ANA001 with a standardized light meal presented at 4 x 250 mg capsules. Each capsule is 250 mg.	Drug: Niclosamide; Niclosamide is an antihelmintic with in-vitro antiviral activity; Other Names: ANA001
Experimental: SAD Cohort 2: ANA001 2000 mg po; Subjects will a 2000 mg single oral dose of ANA001 with a standardized light meal presented at 8 x 250 mg capsules. Each capsule is 250 mg.	Drug: Niclosamide; Niclosamide is an antihelmintic with in-vitro antiviral activity; Other Names: ANA001
Experimental: SAD Cohort 3: ANA001 3000 mg po; Subjects will a 3000 mg single oral dose of ANA001 with a standardized light meal presented at 12 x 250 mg capsules. Each capsule is 250 mg.	Drug: Niclosamide; Niclosamide is an antihelmintic with in-vitro antiviral activity; Other Names: ANA001
Placebo Comparator: SAD Cohorts 1, 2 & 3: Pooled Matching Placebo; Subjects will receive matching placebo hydroxypropylmethylcellulose (HPMC) as a single oral dose (4, 8, or 12 capsules) with a standardized light meal.	Drug: Placebo; Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients; Other Names: Matching Placebo to ANA001
Experimental: MAD Cohort 1: ANA001 1000 mg po BID; Subjects will receive an oral dose of 1000mg ANA001 twice daily (BID) with a standardized light meal for 7 consecutive days. Each dose will be presented as 4 250mg capsules.	Drug: Niclosamide; Niclosamide is an antihelmintic with in-vitro antiviral activity; Other Names: ANA001
Experimental: MAD Cohort 2: ANA001 1000 mg po TID; Subjects will receive an oral dose of 1000mg ANA001 three times daily (TID) with a standardized light meal for 7 consecutive days. Each dose will be presented as 4 250mg capsules.	Drug: Niclosamide; Niclosamide is an antihelmintic with in-vitro antiviral activity; Other Names: ANA001
Placebo Comparator: MAD Cohorts 1 & 2: Pooled Matching Placebo; Subjects will receive an oral dose of matching Placebo to ANA001 two (BID) three times daily (TID) with a standardized light meal for 7 consecutive days. Each dose will be presented as 4 250mg capsules of hydroxypropylmethylcellulose (HPMC)	Drug: Placebo; Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients; Other Names: Matching Placebo to ANA001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent AEs (TEAEs) and Serious treatment-emergent AEs (STEAEs) in the SAD	Baseline to Day 7.
MAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent AEs (TEAEs) and Serious treatment-emergent AEs (STEAEs) in the MAD	Baseline to Day 14.
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	Number of Subjects with Clinically Significant changes in ECG parameters from Baseline (PR, QRS, QT, and QTc intervals)	Baseline to Day 7
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	Number of Subjects with Clinically Significant changes in ECG parameters from Baseline (PR, QRS, QT, and QTc intervals)	Baseline to Day 14
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	Number of Subjects with Clinically Significant changes in Haematology (Basophils (%),Eosinophils (%, Ery. Mean Corpuscular Hemoglobin, Ery. Mean Corpuscular Volume, Erythrocytes (10^12/L), Hematocrit (%), Hemoglobin (g/dL). Hemoglobin (g/dL), Lymphocytes (%), Monocytes (%), Neutrophils (%)' Platelets (10^9/L), Reticulocytes (%))	Baseline to Day 7
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	Number of Subjects with Clinically Significant changes in Haematology (Basophils (%),Eosinophils (%, Ery. Mean Corpuscular Hemoglobin, Ery. Mean Corpuscular Volume, Erythrocytes (10^12/L), Hematocrit (%), Hemoglobin (g/dL). Hemoglobin (g/dL), Lymphocytes (%), Monocytes (%), Neutrophils (%)' Platelets (10^9/L), Reticulocytes (%))	Baseline to Day 14
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	Number of Subjects with Clinically Significant changes in Serum Chemistry (Alanine Aminotransferase (U/L), Alkaline Phosphatase (U/L), Aspartate Aminotransferase (U/L), Bilirubin (mg/dL), Calcium (mg/dL), Creatinine (mg/dL), Direct Bilirubin (mg/dL, Glucose (mg/dL), Potassium (mmol/L), Protein (g/dL), Sodium (mmol/L), Urea Nitrogen (mg/dL)	Baseline to Day 7
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	Number of Subjects with Clinically Significant changes in Serum Chemistry (Alanine Aminotransferase (U/L), Alkaline Phosphatase (U/L), Aspartate Aminotransferase (U/L), Bilirubin (mg/dL), Calcium (mg/dL), Creatinine (mg/dL), Direct Bilirubin (mg/dL, Glucose (mg/dL), Potassium (mmol/L), Protein (g/dL), Sodium (mmol/L), Urea Nitrogen (mg/dL)	Baseline to Day 14
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	Number of Subjects with Clinically Significant changes in Urinalysis (Specific Gravity, Urobilinogen (EU), pH)	Baseline to Day 7
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	Number of Subjects with Clinically Significant changes in Urinalysis (Specific Gravity, Urobilinogen (EU), pH)	Baseline to Day 14
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	Number of Subjects with Clinically Significant changes in Vital Signs from Baseline (Diastolic Blood Pressure, Systolic Blood Pressure (mmHg), Pulse Rate (beats/min), Respiratory Rate (breaths/min))	Baseline to Day 7
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	Number of Subjects with Clinically Significant changes in Vital Signs from Baseline (Diastolic Blood Pressure, Systolic Blood Pressure (mmHg), Pulse Rate (beats/min), Respiratory Rate (breaths/min))	Baseline to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAD: Tmax	Time to reach the maximum plasma concentration (SAD)	PK samples were collected before dosing and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours. A Follow-up sample was taken Day 7 (±2) after dosing.
SAD: Cmax	Maximum plasma concentration during a dosing interval (SAD)	PK samples were collected before dosing and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours. A Follow-up sample was taken Day 7 (±2) after dosing.
SAD: AUC0-t	Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (SAD)	PK samples were collected before dosing and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours. A Follow-up sample was taken Day 7 (±2) after dosing.
SAD: AUC0-∞	Area under the plasma concentration time curve from time 0 extrapolated to infinity, calculated as AUC0-last + Clast/λ, where Clast is the last quantifiable concentration at time t (SAD)	PK samples were collected before dosing and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours. A Follow-up sample was taken Day 7 (±2) after dosing.
SAD: t1/2	Elimination half-life associated with the terminal slope (λ) of the semilogarithmic drug concentration-time curve, calculated as 0.693/λ (SAD)	PK samples were collected before dosing and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours. A Follow-up sample was taken Day 7 (±2) after dosing.
SAD: CL/F	Systemic Clearance (SAD)	PK samples were collected before dosing and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours. A Follow-up sample was taken Day 7 (±2) after dosing.
SAD: Vz/F	Volume of distribution (SAD)	PK samples were collected before dosing and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hours. A Follow-up sample was taken Day 7 (±2) after dosing.
MAD: Tmax Day 1	Time to reach the maximum plasma concentration Day 1	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: Tmax Day 7	Time to reach the maximum plasma concentration (Day 7)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: Cmax Day 1	Maximum plasma concentration during a dosing interval (Day 1)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: For BID but omitting samples at 10, and 12 hours after dosing.
MAD: Cmax Day 7	Maximum plasma concentration during a dosing interval (Day 7)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: AUC0-t Day 1	Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (Day 1)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: AUC0-t Day 7	Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (Day 7)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: AUC0-tau Day 1	Area under the plasma concentration-time curve over the dosing interval at steady-state, calculated from the dosing interval (Day 1)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: AUC0-tau Day 7	Area under the plasma concentration-time curve over the dosing interval at steady-state, calculated from the dosing interval (Day 7)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: t1/2 Day 1	Elimination half-life associated with the terminal slope (λ) of the semilogarithmic drug concentration-time curve, calculated as 0.693/λ (Day 1)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: t1/2 Day 7	Elimination half-life associated with the terminal slope (λ) of the semilogarithmic drug concentration-time curve, calculated as 0.693/λ (Day 7)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: CLss Day 1	Systemic Clearance at steady state (Day 1)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: CLss Day 7	Systemic Clearance at steady state (Day 7)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: Vdss Day 1	Volume of distribution at steady state (Day 1)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.
MAD: Vdss Day 7	Volume of distribution at steady state (Day 7)	BID: Samples on Days 1 and 7 before dosing and at 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after dosing; Days 2, 4, 6, and 8 before dosing and before the 12 h. dose on Days 2, 4, and 6.TID: As BID but omitting samples at 10, and 12 hours after dosing.

Collaborators and Investigators

• Sponsor: NeuroBo Pharmaceuticals Inc.
• Investigators: Study Director: Doug Rank, MD, NeuroBo Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): October 13, 2021
• Study Completion (Actual): October 28, 2022

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 3, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Antiplatyhelmintic Agents; Anticestodal Agents; Niclosamide
• Other Study ID Numbers: ANA001-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No