A Phase I, Single-Center, Open-Label Study Investigating the Excretion Balance, Pharmacokinetics (PK) and Metabolism of a Single Oral Dose of [14C]PCO371 and PK of an Intravenous (IV) Tracer of [14C]PCO371 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Mass balance data for [14C]PCO371 Oral solution in urine
研究概览
简要总结
This is a Phase I single center, open-label, non-randomized study in healthy male subjects, designed to evaluate the mass balance recovery, PK, metabolism and absolute bioavailability of single oral doses of PCO371. It is planned to enroll 12 subjects, with 6 subjects in each of 2 study parts. Subjects in Part 1 will receive a single oral dose of [14C]PCO371 Oral Solution. Subjects in Part 2 will receive a single oral dose of PCO371 capsules, followed by a single intravenous infusion of [14C]PCO371 Solution for Infusion over 10 min, starting 2 h post-oral dose. The study parts may be dosed in any order for logistical reasons (e.g. Part 2 may be dosed before Part 1). No subject will be permitted to take part in both study parts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy males
- •Aged 40 to 60 years inclusive at the time of signing informed consent.
- •Body mass index (BMI) of 18.5 to 30.0 kg/m2 as measured at screening.
- •Must be willing and able to communicate and participate in the whole study.
- •Subjects must have regular bowel movements (i.e. average stool production of >=1 and <=3 stools per day).
- •Must provide written informed consent.
- •Must agree to adhere to the contraception requirements.
- •Subjects must regularly consume 2 or more units of alcohol per week.
排除标准
- •Subjects who have taken any experimental (non-approved) drug (including placebo) either within 90 days before the administration of the study drug, or 6 times the T1/2 of the experimental drug, whichever is longer.
- •Subjects who have previously been administered IMP in this study. Subjects are not permitted to be dosed in both Part 1 and Part 2 of the study.
- •Subjects who have been administered IMP in any 14C-labelled ADME in the last 12 months.
- •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 venipunctures / cannulation as assessed by the investigator or delegate at screening.
- •Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the investigator at screening or admission.
- •Abnormal (outside of reference range) serum calcium or corrected calcium as measured at admission or screening.
- •Elevated (> 2.5 × upper limit of normal [ULN]) alkaline phosphatase at admission or screening. Subjects with Gilbert's syndrome or elevated (above the ULN) aspartate aminotransferase (AST), ALT or total bilirubin at admission or screening.
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
- •Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <60 mL/min using the Cockcroft-Gault equation.
- •Confirmed positive drugs of abuse test result.
- •History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, immunologic, metabolism, endocrine, neurological or psychiatric disorder, as judged by the investigator, blood dyscrasia, risk factors for osteosarcoma as judged by the investigator.
- •Evidence or any history of active diseases that might affect calcium, bone metabolism, or calcium-phosphate homeostasis.
- •Use of anti-coagulants (e.g. heparins, warfarin, and thrombolytic agents), anti-platelet medications (e.g. argatroban and ticlopidine), nonsteroidal anti-inflammatory drugs and aspirin within 2 weeks (or within 6 times the T1/2 of the drug, whichever is longer) prior to study drug administration.
- •Subjects who have taken any inducers of CYP3A4, P glycoprotein (e.g. St. John's wort), or BCRP within 1 month prior to study drug administration, or taken any inhibitors of CYP3A4, P-glycoprotein, or BCRP (including herbal products, diets, and drinks e.g. tonic water) within 2 weeks prior to study drug administration (or within 6 times the T1/2 of the drugs mentioned above, whichever is longer).
研究组 & 干预措施
Mass Balance
Subjects will receive a single oral dose of [14C]PCO371 Oral Solution.
干预措施: [14C]PCO371 (Drug)
Absolute Bioavailability and Mass Balance
Subjects will receive a single oral dose of PCO371 capsules, followed by a single IV infusion of [14C]PCO371 over 10 min, starting 2 h post-oral dose.
干预措施: PCO371 (Drug)
Absolute Bioavailability and Mass Balance
Subjects will receive a single oral dose of PCO371 capsules, followed by a single IV infusion of [14C]PCO371 over 10 min, starting 2 h post-oral dose.
干预措施: [14C]PCO371 (Drug)
结局指标
主要结局
Mass balance data for [14C]PCO371 Oral solution in urine
时间窗: 1 week
Amount of total radioactivity excreted in urine(Ae(urine)) and Ae(urine) expressed as a percentage of the radioactive dose administered (%Ae(urine)), cumulative amount of total radioactivity excreted in urine (CumAe(urine)) and CumAe(urine)expressed as a percentage of the radioactive dose administered (Cum%Ae(urine)) following oral administration of \[14C\]PCO371 Oral Solution.
Mass balance data for [14C]PCO371 Oral solution in feces
时间窗: 5 weeks
Amount of total radioactivity excreted in feces(Ae(feces)) and Ae(feces) expressed as a percentage of the radioactive dose administered (%Ae(feces)), cumulative amount of total radioactivity excreted in feces (CumAe(feces)) and CumAe(feces)expressed as a percentage of the radioactive dose administered (Cum%Ae(feces)) following oral administration of \[14C\]PCO371 Oral Solution.
Mass balance data for [14C]PCO371 Oral solution in urine and feces combined
时间窗: 5 weeks
Amount of total radioactivity excreted in urine and feces combined(Ae(total)) and Ae(total) expressed as a percentage of the radioactive dose administered (%Ae(total)), cumulative amount of total radioactivity excreted in urine and feces combined (CumAe(total)) and CumAe(total)expressed as a percentage of the radioactive dose administered (Cum%Ae(total)) following oral administration of \[14C\]PCO371 Oral Solution.
Absolute bioavailability (F) for PCO371
时间窗: 1 week
Time of maximum observed concentration for PCO371 and a metabolite in plasma and for total radioactivity in plasma and whole blood following oral administration of \[14C\]PCO371 Oral Solution
次要结局
- Pharmacokinetic data for [14C]PCO371 Oral Solution; Tmax(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; AUC ratio(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; Cmax(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; AUC(0-last)(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; AUC(0-inf)(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; T1/2(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; Cmax ratio(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; B:P Cmax ratio(1 week)
- Pharmacokinetic data for [14C]PCO371 Oral Solution; B:P AUC ratio(1 week)
- Metabolite profiling of plasma, urine and feces(1 week)
- Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; C0(1 week)
- Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; AUC(0-last)(1 week)
- Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; AUC(0-inf)(1 week)
- Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; T1/2(1 week)
- Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; CL(1 week)
- Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; Vz(1 week)
- Oral pharmacokinetic data for PCO371 capsule; Tmax(1 week)
- Oral pharmacokinetic data for PCO371 capsule; Cmax(1 week)
- Oral pharmacokinetic data for PCO371 capsule; AUC(0-last)(1 week)
- Oral pharmacokinetic data for PCO371 capsule; AUC(0-inf)(1 week)
- Oral pharmacokinetic data for PCO371 capsule; T1/2(1 week)
- Mass balance data for [14C]PCO371 Solution for Infusion in urine(1 week)
- Mass balance data for [14C]PCO371 Solution for Infusion in feces(5 weeks)
- Safety data for PCO371; Adverse event monitoring(6 weeks)
- Safety data for PCO371; Incidence of laboratory abnormalities(6 weeks)
- Safety data for PCO371; 12-lead ECGs (Ventricular Rate)(6 weeks)
- Safety data for PCO371; 12-lead ECGs (PR interval)(6 weeks)
- Safety data for PCO371; 12-lead ECGs (QRS Duration)(6 weeks)
- Safety data for PCO371; 12-lead ECGs (QT interval)(6 weeks)
- Safety data for PCO371; 12-lead ECGs (QRS Axis)(6 weeks)
- Safety data for PCO371; 12-lead ECGs (QTcF interval)(6 weeks)
- Safety data for PCO371; 12-lead ECGs (Rhythm)(6 weeks)
- Safety data for PCO371; Vital signs (Systolic blood pressure)(6 weeks)
- Safety data for PCO371; Vital signs (Diastolic blood pressure)(6 weeks)
- Safety data for PCO371; Vital signs (Heart Rate)(6 weeks)
- Safety data for PCO371; Vital signs (Oral temperature)(6 weeks)
- Safety data for PCO371; Presense of abnormalities in Physical examinations(6 weeks)