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

NCT04705415 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ANA001-002
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (21)

• SAD: Tmax

  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

  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

  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-∞

  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

  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.

Study Arms (7)

SAD Cohort 1: ANA001 1000 mg po

EXPERIMENTAL

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

SAD Cohort 2: ANA001 2000 mg po

EXPERIMENTAL

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

SAD Cohort 3: ANA001 3000 mg po

EXPERIMENTAL

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

SAD Cohorts 1, 2 & 3: Pooled Matching Placebo

PLACEBO COMPARATOR

Subjects will receive matching placebo hydroxypropylmethylcellulose (HPMC) as a single oral dose (4, 8, or 12 capsules) with a standardized light meal.

Drug: Placebo

MAD Cohort 1: ANA001 1000 mg po BID

EXPERIMENTAL

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

MAD Cohort 2: ANA001 1000 mg po TID

EXPERIMENTAL

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

MAD Cohorts 1 & 2: Pooled Matching Placebo

PLACEBO COMPARATOR

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

Interventions

Niclosamide DRUG

Niclosamide is an antihelmintic with in-vitro antiviral activity

Also known as: ANA001

MAD Cohort 1: ANA001 1000 mg po BID; MAD Cohort 2: ANA001 1000 mg po TID; SAD Cohort 1: ANA001 1000 mg po; SAD Cohort 2: ANA001 2000 mg po; SAD Cohort 3: ANA001 3000 mg po

Placebo DRUG

Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients

Also known as: Matching Placebo to ANA001

MAD Cohorts 1 & 2: Pooled Matching Placebo; SAD Cohorts 1, 2 & 3: Pooled Matching Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign the study informed consent form
• Man or woman, 18 to 65 years of age inclusive at the time of signing the informed consent form
• Overtly healthy as determined by medical evaluation
• Body mass index (BMI) within 18 to 30.0 kg/m2 (inclusive) and body weight not less than 50 kg
• Blood pressure at Screening and Day -1 between 90 and 140 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic.
• 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
• Non-smoker or ex-smoker for \>12 months
• 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
• If female, is not pregnant, not breastfeeding, and meets at least one of the following conditions:

You may not qualify if:

• 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.
• Has known allergy to niclosamide or salicylate-containing medications.
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening.
• Clinically significant abnormal physical examination, vital signs or 12 lead ECG at screening.
• 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.
• 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
• 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.
• Has preplanned surgery or procedures that would interfere with the conduct of the study
• 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

Sponsors & Collaborators

• NeuroBo Pharmaceuticals Inc.: lead

Study Sites (1)

WCCT Global Inc.

Cypress, California, 90630, United States

Location

MeSH Terms

Interventions

Niclosamide

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sr. Vice President Clinical Operations
• Organization: NeurobBo

crinfo@neurobopharma.com

8572991035

Study Officials

• Doug Rank, MD

  NeuroBo Pharmaceuticals Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomized, Double-Blind Study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: January 12, 2021
• Study Start: November 17, 2020
• Primary Completion: October 13, 2021
• Study Completion: October 28, 2022
• Last Updated: February 3, 2025
• Results First Posted: February 3, 2025

Record last verified: 2025-01

Locations

US (1)