Clinical trial NCT04649216: Excretion Balance, PK and Metabolism of a Single Oral Dose of [14C]PCO371
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Chugai Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2020-12-02
Enrollment: 11
Sex: MALE
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Healthy males
2. Aged 40 to 60 years inclusive at the time of signing informed consent.
3. Body mass index (BMI) of 18.5 to 30.0 kg/m2 as measured at screening.
4. Must be willing and able to communicate and participate in the whole study.
5. Subjects must have regular bowel movements (i.e. average stool production of \>=1 and \<=3 stools per day).
6. Must provide written informed consent.
7. Must agree to adhere to the contraception requirements.
8. Subjects must regularly consume 2 or more units of alcohol per week.

Exclusion Criteria:

1. 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.
2. 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.
3. Subjects who have been administered IMP in any 14C-labelled ADME in the last 12 months.
4. 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.
5. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study.
6. Subjects who do not have suitable veins for multiple venipunctures / cannulation as assessed by the investigator or delegate at screening.
7. Clinically significant abnormal clinical chemistry, hematology, coagulation or urinalysis as judged by the investigator at screening or admission.
8. Abnormal (outside of reference range) serum calcium or corrected calcium as measured at admission or screening.
9. 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.
10. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
11. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of \<60 mL/min using the Cockcroft-Gault equation.
12. Confirmed positive drugs of abuse test result.
13. 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.
14. Evidence or any history of active diseases that might affect calcium, bone metabolism, or calcium-phosphate homeostasis.
15. 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.
16. 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).

Primary outcomes:
measure: Mass balance data for [14C]PCO371 Oral solution in urine
timeFrame: 1 week
measure: Mass balance data for [14C]PCO371 Oral solution in feces
timeFrame: 5 weeks
measure: Mass balance data for [14C]PCO371 Oral solution in urine and feces combined
timeFrame: 5 weeks
measure: Absolute bioavailability (F) for PCO371
timeFrame: 1 week
Secondary outcomes:
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; Tmax
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; Cmax
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; AUC(0-last)
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; AUC(0-inf)
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; T1/2
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; Cmax ratio
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; AUC ratio
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; B:P Cmax ratio
timeFrame: 1 week
measure: Pharmacokinetic data for [14C]PCO371 Oral Solution; B:P AUC ratio
timeFrame: 1 week
measure: Metabolite profiling of plasma, urine and feces
timeFrame: 1 week
measure: Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; C0
timeFrame: 1 week
measure: Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; AUC(0-last)
timeFrame: 1 week
measure: Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; AUC(0-inf)
timeFrame: 1 week
measure: Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; T1/2
timeFrame: 1 week
measure: Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; CL
timeFrame: 1 week
measure: Intravenous pharmacokinetic data for [14C]PCO371 Solution for Infusion; Vz
timeFrame: 1 week
measure: Oral pharmacokinetic data for PCO371 capsule; Tmax
timeFrame: 1 week
measure: Oral pharmacokinetic data for PCO371 capsule; Cmax
timeFrame: 1 week
measure: Oral pharmacokinetic data for PCO371 capsule; AUC(0-last)
timeFrame: 1 week
measure: Oral pharmacokinetic data for PCO371 capsule; AUC(0-inf)
timeFrame: 1 week
measure: Oral pharmacokinetic data for PCO371 capsule; T1/2
timeFrame: 1 week
measure: Mass balance data for [14C]PCO371 Solution for Infusion in urine
timeFrame: 1 week
measure: Mass balance data for [14C]PCO371 Solution for Infusion in feces
timeFrame: 5 weeks
measure: Safety data for PCO371; Adverse event monitoring
timeFrame: 6 weeks
measure: Safety data for PCO371; Incidence of laboratory abnormalities
timeFrame: 6 weeks
measure: Safety data for PCO371; 12-lead ECGs (Ventricular Rate)
timeFrame: 6 weeks
measure: Safety data for PCO371; 12-lead ECGs (PR interval)
timeFrame: 6 weeks
measure: Safety data for PCO371; 12-lead ECGs (QRS Duration)
timeFrame: 6 weeks
measure: Safety data for PCO371; 12-lead ECGs (QT interval)
timeFrame: 6 weeks
measure: Safety data for PCO371; 12-lead ECGs (QRS Axis)
timeFrame: 6 weeks
measure: Safety data for PCO371; 12-lead ECGs (QTcF interval)
timeFrame: 6 weeks
measure: Safety data for PCO371; 12-lead ECGs (Rhythm)
timeFrame: 6 weeks
measure: Safety data for PCO371; Vital signs (Systolic blood pressure)
timeFrame: 6 weeks
measure: Safety data for PCO371; Vital signs (Diastolic blood pressure)
timeFrame: 6 weeks
measure: Safety data for PCO371; Vital signs (Heart Rate)
timeFrame: 6 weeks
measure: Safety data for PCO371; Vital signs (Oral temperature)
timeFrame: 6 weeks
measure: Safety data for PCO371; Presense of abnormalities in Physical examinations
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
state: UK
Study officials:
affiliation: clinical-trials@chugai-pharm.co.jp
name: Chugai Pharma Europe Ltd.
role: STUDY_DIRECTOR
References: