A Phase 1, Two-part, Open-label, Single-oral-dose Study to Investigate the Absolute Bioavailability and Absorption, Pharmacokinetics, Distribution, Metabolism, and Excretion of [14C]-Derazantinib in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: Cmax
研究概览
简要总结
This is a Phase 1, two-part, open-label, single centre, single arm study in healthy male subjects to investigate the oral PK, intravenous (IV) PK, mass balance, bioavailability and metabolites profiling and identification of derazantinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy males
- •Age 18 to ≤ 55 years (Part 1)
- •Age 30 to ≤ 65 years (Part 2)
- •Body mass index of 18.0 to 29.0 kg/m² and a minimum body weight of 50 kg
- •Must have regular bowel movements
- •Must agree to adhere to the contraception requirements
排除标准
- •Male subjects with pregnant partners
- •Subjects who have received any investigational medicine in a clinical research study within the previous 3 months
- •Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- •History of any drug or alcohol abuse in the 12 months prior to dosing
- •Regular alcohol consumption in males > 21 units per week
- •Smokers and users of e-cigarettes and nicotine replacement products and those who have used these products within the last 3 months
- •Radiation exposure (diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study
- •Participation in any study involving administration of any [14C]-labelled compound within 12 months prior to screening (Part 1 only)
- •Excessive caffeine consumption within 14 days prior to screening, defined as 800 mg per day (approximately 6 large cups of coffee)
- •Subjects who do not have suitable veins
- •Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the Investigator
- •Confirmed positive drugs of abuse test result
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results, or history of immunodeficiency diseases, including a positive HIV (ELISA and western blot) test result
- •Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of < 70 mL/min using the Cockcroft-Gault equation
- •History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder or current clinical evidence of any corneal or retinal disorder
- •Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
- •Known hypersensitivity or allergy to natural rubber latex
- •History of any food allergies
- •History of clinically significant ECG abnormalities
- •Familial history of sick-sinus syndrome
- •Recent (within the last 3 years) and/or recurrent history of autonomic dysfunction
- •Recent (within the last 3 years) and/or recurrent history of acute or chronic bronchospastic disease (including asthma disease, treated or not treated)
- •History of malignancy of any organ system (other than localised basal cell carcinoma of the skin), treated or untreated, within the past 5 years
- •Use of any prescription drugs (including vaccines), herbal supplements (such as St. John's Wort, homeopathic preparations), within 4 weeks prior to initial dosing, and/or over-the-counter medication, dietary supplements (vitamins and minerals included) within 2 weeks prior to initial dosing
- •Donation or loss of 400 mL or more of blood and/or plasma within 3 months prior to initial dosing
- •Any history or presence of frequent episodes of diarrhoea (defined as an increase of 4 to 6 stools per day over usual individual defecation pattern).
- •Significant illness within 2 weeks prior to initial dosing
- •Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardise the subject in case of participation in the study.
- •NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
研究组 & 干预措施
Single-Arm: Derazantinib (Part 1 and Part 2)
- Part 1: 300 mg Derazantinib oral administration followed by 100 μg [14C]-Derazantinib intravenous microdose
- Part 2: 300 mg [14C]-Derazantinib oral administration
干预措施: Derazantinib capsule (Drug)
Single-Arm: Derazantinib (Part 1 and Part 2)
- Part 1: 300 mg Derazantinib oral administration followed by 100 μg [14C]-Derazantinib intravenous microdose
- Part 2: 300 mg [14C]-Derazantinib oral administration
干预措施: [14C]-Derazantinib solution for infusion (Drug)
Single-Arm: Derazantinib (Part 1 and Part 2)
- Part 1: 300 mg Derazantinib oral administration followed by 100 μg [14C]-Derazantinib intravenous microdose
- Part 2: 300 mg [14C]-Derazantinib oral administration
干预措施: [14C]-Derazantinib capsule (Drug)
结局指标
主要结局
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: Cmax
时间窗: up to Day 50
Assessment of the maximum observed plasma concentration (Cmax)
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: Tmax
时间窗: up to Day 50
Assessment of the time from dosing at which Cmax was apparent (Tmax)
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: t½
时间窗: up to Day 50
Assessment of the apparent terminal elimination half-life (t½)
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: AUC0-t
时间窗: up to Day 50
Assessment of the area under the concentration-time curve from dosing to the last measurable concentration (AUC0-t)
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: AUC0-inf
时间窗: up to Day 50
Assessment of the area under the concentration-time curve from dosing extrapolated to infinity (AUC0-inf)
Assessment of the PK of [14C]-derazantinib: Vss
时间窗: up to Day 50
Assessment of the volume of distribution at steady state (Vss)
Assessment of the PK of total radioactivity, [14C]-derazantinib, derazantinib, and BAL0122840: Tlast
时间窗: up to Day 50
Assessment of the time of the last measurable (positive) concentration (Tlast)
Assessment of the PK of [14C]-derazantinib: CL
时间窗: up to Day 50
Assessment of the total clearance (CL)
Assessment of the PK of [14C]-derazantinib: Vd
时间窗: up to Day 50
Assessment of the volume of distribution (Vd)
Assessment of the PK of derazantinib: CL/F
时间窗: up to Day 50
Apparent total clearance (CL/F)
Assessment of the PK of derazantinib: F
时间窗: up to Day 50
Absolute bioavailability (F)
Assessment of the rate and routes of excretion, and the mass balance of total radioactivity in urine and faeces and in all excreta
时间窗: up to Day 50
Assessment of total radioactivity by measuring the amount excreted (Ae), Ae as a percentage of the administered dose (%Ae), cumulative recovery (CumAe), and cumulative recovery expressed as a percentage of the dose (Cum%Ae)
次要结局
未报告次要终点