An Open-Label, Single-Dose, Single-Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Mass Balance Recovery of Total Radioactivity: CumAe (Urine)
研究概览
简要总结
This single-center, open-label, non randomized Phase I study is being conducted to investigate the pharmacokinetics, mass balance and metabolite profiling and identification after a single oral dose of 100mg of [14C]-MD1003 in 6 healthy males subjects. The radioactivity will be followed in the blood, urine and faeces to study MD1003 metabolism.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 30 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 30 to 65 years of age at the time of signing informed consent
- •Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening
- •Must be willing and able to communicate and participate in the whole study
- •Must have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day)
- •Must provide written informed consent
- •Must agree to adhere to the contraception requirements of the protocol
排除标准
- •Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1
- •Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- •Subjects who have previously been enrolled in this study
- •History of any drug or alcohol abuse in the past 2 years
- •Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
- •A confirmed positive alcohol breath test at screening or admission
- •Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission
- •Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
- •Subjects with pregnant or lactating partners
- •Radiation exposure, including that from the present study, excluding background radiation but including 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
- •Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
- •Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are allowed
- •Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in the protocol)
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
- •Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <80 mL/min using the Cockcroft-Gault equation
- •History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
- •Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
- •Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
- •Donation or loss of greater than 400 mL of blood within the previous 3 months
- •Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g of paracetamol per day), herbal remedies, vitamin B5 or dietary supplements containing lipoic acid in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the PI
- •Subjects who have had any intake of biotin (including as a nutritional supplement) in the 14 days before IMP administration
- •Failure to satisfy the investigator of fitness to participate for any other reason
研究组 & 干预措施
MD1003
radiolabeled 14C MD1003 (High Dose Biotin) 100mg
干预措施: [14C]-MD1003 (Drug)
结局指标
主要结局
Mass Balance Recovery of Total Radioactivity: CumAe (Urine)
时间窗: Pre-dose to 312 hours post-dose
Cumulative amount of total radioactivity excreted in urine Measured at 0/12/24/48/72/96/120/144/168/192/216/240/264/288/312 hours
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Faeces)
时间窗: Pre-dose to 312 hours post dose
Cumulative amount of total radioactivity excreted in faeces expressed as a percentage of the radioactive dose administered Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: CumAe(Total)
时间窗: Pre-dose to 312 hours post dose
Cumulative amount of total radioactivity excreted in urine and faeces combined Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: CumAe (Faeces)
时间窗: Pre-dose to 312 hours post-dose
Cumulative amount of total radioactivity excreted in faeces Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Total)
时间窗: Pre-dose to 312 hours post dose
Cumulative amount of total radioactivity excreted in urine and faeces combined expressed as a percentage of the radioactive dose administered Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Urine)
时间窗: Pre-dose to 312 hours post dose
Cumulative amount of total radioactivity excreted in urine expressed as a percentage of the radioactive dose administered Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
次要结局
- Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity(Pre-dose to 168 hours)
- Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-last)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity(Pre-dose to 168 hours)
- Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity(Pre-dose to 168 hours)
- Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity(Pre-dose to 168 hours)
- Area Under Plasma Concentration Curve From 0 Time Extrapolated to Infinity (AUC(0-inf)) for MD1003 and Total Radioactivity(Pre-dose to 168 hours)
- Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-12)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity(Pre-dose to 168 hours)
- MPR AUC(0-inf) for Bisnorbiotin and Biotin Sulfoxide(Pre-dose to 168 hours)
- Number of Subjects With Adverse Events (AEs)(Overall period)
- Change From Baseline in Heart Rate in Beats Per Minute(Pre-dose to Day 10)
- Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity(Pre-dose to 168 hours)
- Plasma Clearance (Vz/F) for MD1003(Pre-dose to 168 hours)
- Change From Baseline in Systolic Blood Pressure in mmHg(Pre-dose to Day 10)
- Whole Blood: Plasma Concentration Ratios of Total Radioactivity(Pre-dose to 168 hours post-dose)
- Change From Baseline in Diastolic Blood Pressure in mmHg(Pre-dose to Day 10)
- Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity(Pre-dose to 168 hours)
- Percentage of AUC(0-extrap) Extrapolated Beyond the Last Measurable Concentration for MD1003 and Total Radioactivity(Pre-dose to 168 hours)
- Plasma Clearance (CL/F) for MD1003(Pre-dose to 168 hours)
- MPR Cmax for Bisnorbiotin and Biotin Sulfoxide(Pre-dose to 168 hours)
- Number of Subjects With Adverse Drug Reactions as Assessed by Investigator(Overall period)
- Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds(Pre-dose to Day 10)