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
Overview
- Phase
- Phase 1
- Intervention
- [14C]PCO371
- Conditions
- Healthy Volunteers
- Sponsor
- Chugai Pharmaceutical
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Mass balance data for [14C]PCO371 Oral solution in urine
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Mass Balance
Subjects will receive a single oral dose of \[14C\]PCO371 Oral Solution.
Intervention: [14C]PCO371
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.
Intervention: PCO371
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.
Intervention: [14C]PCO371
Outcomes
Primary Outcomes
Mass balance data for [14C]PCO371 Oral solution in urine
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Secondary Outcomes
- 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)