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

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

Detailed Description
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: Niclosamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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: 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: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANA001<br>For the single ascending dose (SAD) portion of the study, subjects will receive their assigned treatment as a single oral dose (1000 mg, 2000 mg, or 3000 mg of ANA001) with a standardized light meal. Each capsule is 250 mg. For the multiple ascending dose (MAD) portion of the study, subjects will receive their assigned treatment twice daily (BID) or thrice daily (TID) (total daily dose is to be determined following the completion of the SAD portion of the study and will not exceed 2000 mg ANA001) with a standardized light meal for 7 consecutive days. Each capsule is 250 mg. | Drug: Niclosamide<br>* Niclosamide is an antihelmintic with in-vitro antiviral activity<br>* Other names: ANA001;|
| Placebo Comparator: Matching Placebo<br>For the single ascending dose (SAD) portion of the study, subjects will receive their assigned matching placebo (hydroxypropylmethylcellulose (HPMC) as a single dose (4, 8, or 12 capsules) with a standardized light meal. For the multiple ascending dose (MAD) portion of the study, subjects will receive their assigned matching placebo (hydroxypropylmethylcellulose (HPMC) dose twice daily (BID) or thrice daily (TID) with a standardized light meal. | Drug: Placebo<br>* Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of ANA001 as measured by the incidence of treatment-emergent AEs (TEAEs) and serious adverse events (SAEs) | Incidence of treatment-emergent AEs (TEAEs) and serious adverse events (SAEs) | Baseline to Day 7 for SAD portion; Baseline to Day 15 for MAD portion | 
| Safety and tolerability of ANA001 as measured by the incidence of study drug discontinuations due to an adverse event (AE) (MAD portion only) | Incidence of study drug discontinuations due to an Adverse Event (AE) | Baseline to Day 15 | 
| Safety and tolerability of ANA001 as measured by the use of concomitant medications | Incidence in the use of concomitant medications | Baseline to Day 7 for SAD portion; Baseline to Day 15 for MAD portion | 
| Safety and tolerability of ANA001 as measured by the change from baseline in clinical laboratory test results | Incidence of change in clinical laboratory test results (hematology, serum chemistry, urinalysis) | Baseline to Day 7 for SAD portion; Baseline to Day 15 for MAD portion | 
| Safety and tolerability of ANA001 as measured by the change from baseline in vital signs | Incidence of change from baseline in vital signs (oral temperature, pulse rate, respiratory rate, and blood pressure) | Baseline to Day 7 for SAD portion; Baseline to Day 15 for MAD portion | 
| Safety and tolerability of ANA001 as measured by the change in ECG parameters | Incidence of change from baseline in ECG parameters (PR, QRS, QT, and QTc intervals) | Baseline to Day 1 for SAD portion; Baseline to Day 7 for MAD portion | 
| Safety and tolerability of ANA001 as measured by the change incidence of physical example findings | Incidence of physical exam findings | Baseline to Day 1 for SAD portion; Baseline to Day 7 for MAD portion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of ANA001 as measured by plasma concentrations | Plasma concentrations of ANA001 | single ascending dose (Day 1); multiple ascending dose (Day 1 to 8) |