AM1476 - A Phase I, Double-blind, Placebo-controlled, Single- and Multiple-oral Dose, Safety, Tolerability, and Pharmacokinetic Study in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AnaMar AB
- 入组人数
- 97
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events
研究概览
简要总结
This is a First in Human (FIH), double-blind, randomised, placebo-controlled study designed to evaluate safety, tolerability and pharmacokinetics (PK) of single and multiple ascending oral doses of AM1476 in healthy subjects.
详细描述
Part A (SAD); In the SAD part of the study, single oral doses of AM1476 will be administered in up to 9 sequential groups, each consisting of 8 subjects randomised to receive either AM1476 or placebo in a 3:1 ratio. The first 2 subjects in each group will be dosed in a sentinel fashion, 1 subject will receive AM1476 and the other will receive placebo as randomised.
Part B (MAD); The MAD part of the study will explore multiple ascending dosing of AM1476 for 10 days. AM1476 will be administered in up to 6 sequential groups, each consisting of 8 subjects randomised to receive either AM1476 or placebo in a 3:1 ratio.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Males or females, of any race, between 18 and 60 years of age, inclusive.
- •A body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
- •In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital non-haemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening and/or Check-in (Day -1) as assessed by the Investigator (or designee).
- •Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception as detailed in Appendix
- •Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
- •Exclusion Criteria
- •Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
- •History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
- •Any of the following observed in at least 2 of 3 ECG measurements performed:
- •QTcF > 450 msec.
- •QRS duration > 110 msec.
- •PR interval > 220 msec.
- •findings which would make QTc measurements difficult or QTc data uninterpretable.
- •Any history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).
- •Any history or current controlled or uncontrolled hypertension or systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg confirmed by repeat measurement.
- •History of alcoholism or drug/chemical abuse within 2 years prior to Check-in (Day -1).
- •Alcohol consumption of > 21 units per week for males and > 14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
- •Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Check-in (Day -1).
- •Positive hepatitis panel and/or positive human immunodeficiency virus test (Appendix 2).
- •Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
- •Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 30 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
- •Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
- •Use or intend to use slow release medications/products considered to still be active within 14 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee).
- •Use or intend to use any non-prescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee).
- •Use of tobacco- or nicotine-containing products within 3 months prior to Check-in (Day -1) or positive cotinine at Screening or Check-in (Day -1).
- •Ingestion of poppy seeds, Seville orange, or grapefruit-containing foods or beverages within 7 days prior to Check-in (Day -1).
- •Subjects who are vegetarians, vegans, or are unable to consume the high-fat breakfast (subjects who will participate in a food-effect evaluation only).
- •Receipt of blood products within 2 months prior to Check-in (Day -1).
- •Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
- •Poor peripheral venous access.
- •Have previously completed or withdrawn from this study or any other study investigating AM1476, and have previously received AM
- •Subjects who are not willing to minimise or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) following administration of study drug until 2 weeks after the last dose.
- •Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
排除标准
- 未提供
研究组 & 干预措施
Part A, Group 3: AM1476 25 mg
Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 1: AM1476 1 mg
Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 2: AM1476 5 mg
Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 4: AM1476 125 mg
Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 5: AM1476 375 mg
Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 6: AM1476 650 mg
Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 7: AM1476 950 mg
Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 8: AM1476 1500 mg
Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Group 9: AM1476 2400 mg
Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state
干预措施: AM1476 (Drug)
Part A, Groups 1 to 9: Placebo
Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state
干预措施: Placebo (Drug)
Part B, Group 1: AM1476 100 mg QD (once daily)
Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state
干预措施: AM1476 (Drug)
Part B, Group 2: AM1476 375 mg BID (twice daily)
Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state
干预措施: AM1476 (Drug)
Part B, Group 3: AM1476 500 mg BID
Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state
干预措施: AM1476 (Drug)
Part B, Groups 1 to 3: Placebo
Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events
时间窗: Through study completion, an average of 7 weeks
A treatment-emergent adverse-event (TEAE) was defined as an adverse event that started during or after first dosing, or started prior to first dosing and increased in severity after first dosing.
次要结局
- T½(Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.)
- AUC0-tlast(From pre-dose to up to 48 hours post-dose)
- Tmax(Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.)
- Cmax(Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.)
- AUC0-tau(Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.)
- CL/F(Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.)
- Vz/F(Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose.)