Clinical trial NCT04705415: A Single and Multiple Ascending Dose Study of Niclosamide in Healthy Volunteers
Official title: A Randomized, Double-Blind, Single and Multiple Ascending Dose Study to Assess the Safety and Pharmacokinetics of Niclosamide in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: NeuroBo Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-12
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: SAD: Number of Subjects Reporting TEAEs and STEAEs
timeFrame: Baseline to Day 7.
measure: MAD: Number of Subjects Reporting TEAEs and STEAEs
timeFrame: Baseline to Day 14.
measure: SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters
timeFrame: Baseline to Day 7
measure: MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters
timeFrame: Baseline to Day 14
measure: SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology
timeFrame: Baseline to Day 7
measure: MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology
timeFrame: Baseline to Day 14
measure: SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry
timeFrame: Baseline to Day 7
measure: MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry
timeFrame: Baseline to Day 14
measure: SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis
timeFrame: Baseline to Day 7
measure: MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis
timeFrame: Baseline to Day 14
measure: SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs
timeFrame: Baseline to Day 7
measure: MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs
timeFrame: Baseline to Day 14
Secondary outcomes:
measure: SAD: Tmax
timeFrame: 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.
measure: SAD: Cmax
timeFrame: 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.
measure: SAD: AUC0-t
timeFrame: 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.
measure: SAD: AUC0-∞
timeFrame: 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.
measure: SAD: t1/2
timeFrame: 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.
measure: SAD: CL/F
timeFrame: 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.
measure: SAD: Vz/F
timeFrame: 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.
measure: MAD: Tmax Day 1
timeFrame: 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.
measure: MAD: Tmax Day 7
timeFrame: 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.
measure: MAD: Cmax Day 1
timeFrame: 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.
measure: MAD: Cmax Day 7
timeFrame: 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.
measure: MAD: AUC0-t Day 1
timeFrame: 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.
measure: MAD: AUC0-t Day 7
timeFrame: 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.
measure: MAD: AUC0-tau Day 1
timeFrame: 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.
measure: MAD: AUC0-tau Day 7
timeFrame: 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.
measure: MAD: t1/2 Day 1
timeFrame: 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.
measure: MAD: t1/2 Day 7
timeFrame: 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.
measure: MAD: CLss Day 1
timeFrame: 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.
measure: MAD: CLss Day 7
timeFrame: 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.
measure: MAD: Vdss Day 1
timeFrame: 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.
measure: MAD: Vdss Day 7
timeFrame: 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.
Other outcomes:
Locations:
city: Cypress
country: United States
facility: WCCT Global Inc.
state: California
Study officials:
affiliation: NeuroBo Pharmaceuticals Inc.
name: Doug Rank, MD
role: STUDY_DIRECTOR
References: