A Randomized, Double-Blind, Single and Multiple Ascending Dose Study to Assess the Safety and Pharmacokinetics of Niclosamide in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- SAD: Number of Subjects Reporting TEAEs and STEAEs
研究概览
简要总结
A single and multiple ascending dose study of ANA001 in healthy adults to assess the safety and pharmacokinetics
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Randomized, Double-Blind Study
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
- •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.
排除标准
- •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
- •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
研究组 & 干预措施
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.
干预措施: Niclosamide (Drug)
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.
干预措施: Niclosamide (Drug)
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.
干预措施: Niclosamide (Drug)
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.
干预措施: Niclosamide (Drug)
SAD Cohorts 1, 2 & 3: Pooled Matching Placebo
Subjects will receive matching placebo hydroxypropylmethylcellulose (HPMC) as a single oral dose (4, 8, or 12 capsules) with a standardized light meal.
干预措施: Placebo (Drug)
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.
干预措施: Niclosamide (Drug)
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)
干预措施: Placebo (Drug)
结局指标
主要结局
SAD: Number of Subjects Reporting TEAEs and STEAEs
时间窗: Baseline to Day 7.
Number of Subjects Reporting treatment-emergent AEs (TEAEs) and Serious treatment-emergent AEs (STEAEs) in the SAD
SAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in ECG Parameters
时间窗: 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
时间窗: Baseline to Day 14
Number of Subjects with Clinically Significant changes in ECG parameters from Baseline (PR, QRS, QT, and QTc intervals)
MAD: Number of Subjects Reporting TEAEs and STEAEs
时间窗: 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 Haematology
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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))
MAD: Safety and Tolerability of ANA001 as Measured by Clinically Significant Changes in Vital Signs
时间窗: 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))
次要结局
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)