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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04705415

Enrollment

Registered

2021-01-12

Start date

2020-11-17

Completion date

2022-10-28

Last updated

2025-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

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.

Interventions

DRUGNiclosamide

Niclosamide is an antihelmintic with in-vitro antiviral activity

DRUGPlacebo

Matching hydroxypropylmethylcellulose HPMC capsules with no active ingredients

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Masking description

Randomized, Double-Blind Study

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

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

Design outcomes

Primary

Measure	Time frame	Description
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	Baseline to Day 14	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))
SAD: Number of Subjects Reporting TEAEs and STEAEs	Baseline to Day 7.	Number of Subjects Reporting treatment-emergent AEs (TEAEs) and Serious treatment-emergent AEs (STEAEs) in the SAD
MAD: Number of Subjects Reporting TEAEs and STEAEs	Baseline to Day 14.	Number of Subjects Reporting treatment-emergent AEs (TEAEs) and Serious treatment-emergent AEs (STEAEs) in the MAD
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	Baseline to Day 7	Number of Subjects with Clinically Significant changes in ECG parameters from Baseline (PR, QRS, QT, and QTc intervals)
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	Baseline to Day 14	Number of Subjects with Clinically Significant changes in ECG parameters from Baseline (PR, QRS, QT, and QTc intervals)
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	Baseline to Day 7	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 (%))
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	Baseline to Day 14	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 (%))
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	Baseline to Day 7	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)
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	Baseline to Day 14	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)
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	Baseline to Day 7	Number of Subjects with Clinically Significant changes in Urinalysis (Specific Gravity, Urobilinogen (EU), pH)
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	Baseline to Day 14	Number of Subjects with Clinically Significant changes in Urinalysis (Specific Gravity, Urobilinogen (EU), pH)
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	Baseline to Day 7	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))

Secondary

Measure	Time frame	Description
MAD: AUC0-t 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.	Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (Day 7)
MAD: AUC0-tau 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.	Area under the plasma concentration-time curve over the dosing interval at steady-state, calculated from the dosing interval (Day 1)
MAD: AUC0-tau 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.	Area under the plasma concentration-time curve over the dosing interval at steady-state, calculated from the dosing interval (Day 7)
MAD: t1/2 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.	Elimination half-life associated with the terminal slope (λ) of the semilogarithmic drug concentration-time curve, calculated as 0.693/λ (Day 1)
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.	Maximum plasma concentration during a dosing interval (SAD)
MAD: CLss 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.	Systemic Clearance at steady state (Day 1)
MAD: CLss 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.	Systemic Clearance at steady state (Day 7)
MAD: Vdss 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.	Volume of distribution at steady state (Day 1)
MAD: Vdss 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.	Volume of distribution at steady state (Day 7)
MAD: t1/2 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.	Elimination half-life associated with the terminal slope (λ) of the semilogarithmic drug concentration-time curve, calculated as 0.693/λ (Day 7)
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.	Time to reach the maximum plasma concentration (SAD)
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.	Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (SAD)
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.	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)
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.	Elimination half-life associated with the terminal slope (λ) of the semilogarithmic drug concentration-time curve, calculated as 0.693/λ (SAD)
SAD: CL/F	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.	Systemic Clearance (SAD)
SAD: Vz/F	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.	Volume of distribution (SAD)
MAD: Tmax 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.	Time to reach the maximum plasma concentration Day 1
MAD: Tmax 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.	Time to reach the maximum plasma concentration (Day 7)
MAD: Cmax 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.	Maximum plasma concentration during a dosing interval (Day 1)
MAD: Cmax 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.	Maximum plasma concentration during a dosing interval (Day 7)
MAD: AUC0-t 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.	Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (Day 1)

Countries

United States

Participant flow

Participants by arm

Arm	Count
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	8
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.	8
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.	8
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo A matching placebo to a single oral 3000mg dose of 1000mg was administered with a standardized light meal (500 to 750 cal) after an overnight fast of at least 10 hours.	6
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	9
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.	9
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)	6
Total	54

Baseline characteristics

Characteristic	SAD Cohort 2: ANA001 2000 mg po	SAD Cohort 3: ANA001 3000 mg po	SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	MAD Cohort 1: ANA001 1000 mg po BID	MAD Cohort 2: ANA001 1000 mg po TID	MAD Cohorts 1 & 2: Pooled Matching Placebo	SAD Cohort 1: ANA001 1000 mg po	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	8 Participants	8 Participants	6 Participants	9 Participants	9 Participants	6 Participants	8 Participants	54 Participants
Age, Continuous	41.6 Years STANDARD_DEVIATION 16.3	45.8 Years STANDARD_DEVIATION 11.6	47.2 Years STANDARD_DEVIATION 12.8	45.8 Years STANDARD_DEVIATION 13.3	41.8 Years STANDARD_DEVIATION 12.4	38.2 Years STANDARD_DEVIATION 6	44.3 Years STANDARD_DEVIATION 13.9	43.6 Years STANDARD_DEVIATION 12.5
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants	2 Participants	1 Participants	3 Participants	2 Participants	1 Participants	3 Participants	16 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants	6 Participants	5 Participants	6 Participants	7 Participants	5 Participants	5 Participants	38 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants	2 Participants	6 Participants
Race (NIH/OMB) Black or African American	1 Participants	1 Participants	0 Participants	3 Participants	3 Participants	3 Participants	0 Participants	11 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	3 Participants
Race (NIH/OMB) White	6 Participants	6 Participants	3 Participants	6 Participants	5 Participants	1 Participants	5 Participants	32 Participants
Region of Enrollment United States	8 participants	8 participants	6 participants	9 participants	9 participants	6 participants	8 participants	54 participants
Sex: Female, Male Female	4 Participants	4 Participants	3 Participants	5 Participants	4 Participants	3 Participants	1 Participants	24 Participants
Sex: Female, Male Male	4 Participants	4 Participants	3 Participants	4 Participants	5 Participants	3 Participants	7 Participants	30 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8	0 / 8	0 / 6	0 / 9	0 / 9	0 / 6
other Total, other adverse events	0 / 8	0 / 8	0 / 8	1 / 6	3 / 9	3 / 9	1 / 6
serious Total, serious adverse events	0 / 8	0 / 8	0 / 8	0 / 6	0 / 9	0 / 9	0 / 6

Outcome results

Primary

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

Time frame: Baseline to Day 14.

Arm	Measure	Group	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	MAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting TEAEs	3 participants
SAD Cohort 1: ANA001 1000 mg po	MAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting STEAEs	0 participants
SAD Cohort 2: ANA001 2000 mg po	MAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting TEAEs	3 participants
SAD Cohort 2: ANA001 2000 mg po	MAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting STEAEs	0 participants
SAD Cohort 3: ANA001 3000 mg po	MAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting TEAEs	1 participants
SAD Cohort 3: ANA001 3000 mg po	MAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting STEAEs	0 participants

Primary

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)

Time frame: Baseline to Day 14

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	0 participants
SAD Cohort 2: ANA001 2000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	0 participants
SAD Cohort 3: ANA001 3000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	0 participants

Primary

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 (%))

Time frame: Baseline to Day 14

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	0 participants
SAD Cohort 2: ANA001 2000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	0 participants
SAD Cohort 3: ANA001 3000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	0 participants

Primary

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)

Time frame: Baseline to Day 14

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	0 participants
SAD Cohort 2: ANA001 2000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	0 participants
SAD Cohort 3: ANA001 3000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	0 participants

Primary

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)

Time frame: Baseline to Day 14

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	0 participants
SAD Cohort 2: ANA001 2000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	0 participants
SAD Cohort 3: ANA001 3000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	0 participants

Primary

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))

Time frame: Baseline to Day 14

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	0 participants
SAD Cohort 2: ANA001 2000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	0 participants
SAD Cohort 3: ANA001 3000 mg po	MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	0 participants

Primary

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

Time frame: Baseline to Day 7.

Arm	Measure	Group	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent AEs (TEAEs)	0 participants
SAD Cohort 1: ANA001 1000 mg po	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent Serious AEs (STEAEs)	0 participants
SAD Cohort 2: ANA001 2000 mg po	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent Serious AEs (STEAEs)	0 participants
SAD Cohort 2: ANA001 2000 mg po	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent AEs (TEAEs)	0 participants
SAD Cohort 3: ANA001 3000 mg po	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent AEs (TEAEs)	0 participants
SAD Cohort 3: ANA001 3000 mg po	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent Serious AEs (STEAEs)	0 participants
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent AEs (TEAEs)	1 participants
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	SAD: Number of Subjects Reporting TEAEs and STEAEs	Number of Subjects Reporting treatment-emergent Serious AEs (STEAEs)	0 participants

Primary

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)

Time frame: Baseline to Day 7

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	0 participants
SAD Cohort 2: ANA001 2000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	0 participants
SAD Cohort 3: ANA001 3000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	0 participants
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters	0 participants

Primary

SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology

Time frame: Baseline to Day 7

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	0 participants
SAD Cohort 2: ANA001 2000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	0 participants
SAD Cohort 3: ANA001 3000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	0 participants
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Haematology	0 participants

Primary

SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry

Time frame: Baseline to Day 7

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	0 participants
SAD Cohort 2: ANA001 2000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	0 participants
SAD Cohort 3: ANA001 3000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	0 participants
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Serum Chemistry	0 participants

Primary

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)

Time frame: Baseline to Day 7

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	0 participants
SAD Cohort 2: ANA001 2000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	0 participants
SAD Cohort 3: ANA001 3000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	0 participants
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Urinalysis	0 participants

Primary

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))

Time frame: Baseline to Day 7

Arm	Measure	Value (NUMBER)
SAD Cohort 1: ANA001 1000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	0 participants
SAD Cohort 2: ANA001 2000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	0 participants
SAD Cohort 3: ANA001 3000 mg po	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	0 participants
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo	SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs	0 participants

Secondary

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)

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: AUC0-tau Day 1	1630 h*ng/mL	Standard Deviation 500
SAD Cohort 2: ANA001 2000 mg po	MAD: AUC0-tau Day 1	1680 h*ng/mL	Standard Deviation 1810

Secondary

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)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: AUC0-tau Day 7	1100 h*ng/mL	Standard Deviation 480
SAD Cohort 2: ANA001 2000 mg po	MAD: AUC0-tau Day 7	992 h*ng/mL	Standard Deviation 250

Secondary

MAD: AUC0-t Day 1

Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (Day 1)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: AUC0-t Day 1	1630 h*ng/mL	Standard Deviation 499
SAD Cohort 2: ANA001 2000 mg po	MAD: AUC0-t Day 1	1360 h*ng/mL	Standard Deviation 968

Secondary

MAD: AUC0-t Day 7

Area under the plasma concentration-time curve from time 0 to time the last quantifiable concentration (Day 7)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: AUC0-t Day 7	1100 h*ng/mL	Standard Deviation 481
SAD Cohort 2: ANA001 2000 mg po	MAD: AUC0-t Day 7	993 h*ng/mL	Standard Deviation 250

Secondary

MAD: CLss Day 1

Systemic Clearance at steady state (Day 1)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: CLss Day 1	677 L/h	Standard Deviation 246
SAD Cohort 2: ANA001 2000 mg po	MAD: CLss Day 1	1200 L/h	Standard Deviation 928

Secondary

MAD: CLss Day 7

Systemic Clearance at steady state (Day 7)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: CLss Day 7	1060 L/h	Standard Deviation 410
SAD Cohort 2: ANA001 2000 mg po	MAD: CLss Day 7	1070 L/h	Standard Deviation 287

Secondary

MAD: Cmax Day 1

Maximum plasma concentration during a dosing interval (Day 1)

Time frame: 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.

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: Cmax Day 1	332 ng/mL	Standard Deviation 110
SAD Cohort 2: ANA001 2000 mg po	MAD: Cmax Day 1	259 ng/mL	Standard Deviation 158

Secondary

MAD: Cmax Day 7

Maximum plasma concentration during a dosing interval (Day 7)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: Cmax Day 7	234 ng/mL	Standard Deviation 77.9
SAD Cohort 2: ANA001 2000 mg po	MAD: Cmax Day 7	235 ng/mL	Standard Deviation 70.9

Secondary

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)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: t1/2 Day 1	1.8 h	Standard Deviation 0.595
SAD Cohort 2: ANA001 2000 mg po	MAD: t1/2 Day 1	4.82 h	Standard Deviation 2.94

Secondary

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)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: t1/2 Day 7	2.83 h	Standard Deviation 1.33
SAD Cohort 2: ANA001 2000 mg po	MAD: t1/2 Day 7	2.16 h	Standard Deviation 0.194

Secondary

MAD: Tmax Day 1

Time to reach the maximum plasma concentration Day 1

Arm	Measure	Value (MEDIAN)
SAD Cohort 1: ANA001 1000 mg po	MAD: Tmax Day 1	4 h
SAD Cohort 2: ANA001 2000 mg po	MAD: Tmax Day 1	4 h

Secondary

MAD: Tmax Day 7

Time to reach the maximum plasma concentration (Day 7)

Arm	Measure	Value (MEDIAN)
SAD Cohort 1: ANA001 1000 mg po	MAD: Tmax Day 7	4 h
SAD Cohort 2: ANA001 2000 mg po	MAD: Tmax Day 7	2 h

Secondary

MAD: Vdss Day 1

Volume of distribution at steady state (Day 1)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: Vdss Day 1	1920 L	Standard Deviation 788
SAD Cohort 2: ANA001 2000 mg po	MAD: Vdss Day 1	6200 L	Standard Deviation 3750

Secondary

MAD: Vdss Day 7

Volume of distribution at steady state (Day 7)

Arm	Measure	Value (MEAN)	Dispersion
SAD Cohort 1: ANA001 1000 mg po	MAD: Vdss Day 7	4080 L	Standard Deviation 2010
SAD Cohort 2: ANA001 2000 mg po	MAD: Vdss Day 7	3590 L	Standard Deviation 874

Secondary

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)