Excretion Balance, PK and Metabolism of a Single Oral Dose of [14C]PCO371

NCT04649216 | Completed Phase 1 FDA Drug

• 1 other identifier: PCO006EU
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• Mass balance data for [14C]PCO371 Oral solution in urine

  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.

  1 week

• Mass balance data for [14C]PCO371 Oral solution in feces

  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.

  5 weeks

• Mass balance data for [14C]PCO371 Oral solution in urine and feces combined

  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.

  5 weeks

• Absolute bioavailability (F) for PCO371

  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

  1 week

Secondary Outcomes (37)

• Pharmacokinetic data for [14C]PCO371 Oral Solution; Tmax

  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

Study Arms (2)

Mass Balance

EXPERIMENTAL

Subjects will receive a single oral dose of \[14C\]PCO371 Oral Solution.

Drug: [14C]PCO371

Absolute Bioavailability and Mass Balance

EXPERIMENTAL

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.

Drug: PCO371; Drug: [14C]PCO371

Interventions

PCO371 DRUG

PCO371 Capsule

Absolute Bioavailability and Mass Balance

[14C]PCO371 DRUG

\[14C\]PCO371 Oral solution

Mass Balance

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chugai Pharmaceutical: lead

Study Sites (1)

Quotient Sciences

Nottingham, UK, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

PCO371

Study Officials

• Chugai Pharma Europe Ltd.

  clinical-trials@chugai-pharm.co.jp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2020
• First Posted: December 2, 2020
• Study Start: November 25, 2020
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: March 1, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)