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

NeuroBo Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: Niclosamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04705415

ANA001-002

Details and patient eligibility

About

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

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

54 participants in 7 patient groups, including a placebo group

SAD Cohort 1: ANA001 1000 mg po

Experimental group

Description:

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.

Treatment:

Drug: Niclosamide

SAD Cohort 2: ANA001 2000 mg po

Experimental group

Description:

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.

Treatment:

Drug: Niclosamide

SAD Cohort 3: ANA001 3000 mg po

Experimental group

Description:

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.

Treatment:

Drug: Niclosamide

SAD Cohorts 1, 2 & 3: Pooled Matching Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

MAD Cohort 1: ANA001 1000 mg po BID

Experimental group

Description:

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.

Treatment:

Drug: Niclosamide

MAD Cohort 2: ANA001 1000 mg po TID

Experimental group

Description:

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.

Treatment:

Drug: Niclosamide

MAD Cohorts 1 & 2: Pooled Matching Placebo

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo