Clinical trial NCT02418650: Mass Balance, Pharmacokinetics, Biotransformation and Bioavailability Study of ODM-201 in Healthy Male Subjects
Official title: A Two-Part Open-Label, Single-Centre Mass Balance, Pharmacokinetics, Biotransformation and Absolute Bioavailability Study of ODM-201 in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: volunteers
Lead sponsor: Orion Corporation, Orion Pharma
Sponsor class: INDUSTRY
Collaborators: name: Bayer
First posted: 2015-04-16
Enrollment: 12
Sex: MALE
Minimum age (years): 50
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: A study to investigate absolute bioavailability of ODM-201 and to determine the mass balance and routes of excretion of ODM-201 in healthy volunteers.

Detailed description: 6 healthy male subjects will be enrolled in part 1 and part 2 of the study, respectively

Eligibility criteria: Key Inclusion Criteria:

* Healthy males
* Aged 50 to 65 years (inclusive)
* Normal weight defined as a body mass index (BMI) of \>18.5 and \<32.0 kg/m2
* Weight 55 to 100 kg (inclusive)
* Adequate method of contraception during the study and for a period of 6 months after study drug administration

Key exclusion Criteria:

* Evidence of clinically significant disease
* Intake of any medication that could affect the outcome of the study
* Known hypersensitivity to the active substances or the excipients of the drug or any serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
* History of anaphylactic/anaphylactoid reactions
* Clinically significant abnormal biochemistry, haematology or urinalysis
* Current or history of any drug or alcohol abuse in the past 2 years
* Regular alcohol consumption \>21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
* Current use or use within the last 12 months of nicotine products
* Positive drugs of abuse test result
* Positive hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus results
* Presence or history of clinically significant allergy requiring treatment

Primary outcomes:
measure: Amount of 14C-ODM-201 dose excreted and cumulative amount excreted in urine and faeces and total. Amount excreted and cumulative amount excreted in urine, faeces and total expressed as a percentage of the administered dose.
timeFrame: Urine and faecal samples are collected baseline (Day-1) 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing
Secondary outcomes:
Other outcomes:
measure: Metabolite profile of 14C-ODM-201 in plasma, urine and faeces
timeFrame: up to 14 days post-dose after oral solution dosing
measure: Maximum concentration (Cmax) of 14C-radioactivity in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing
measure: Time to maximum concentration (tmax) of 14C-radioactivity in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing
measure: Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-radioactivity in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing
measure: Half life (t1/2) of 14C-radioactivity in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 14 day post-dose after oral solution dosing
measure: Maximum concentration (Cmax) of ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Time to maximum concentration (tmax) of ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Area under the plasma concentration-time curve (AUC(0-t)) of ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Half life (t1/2) of ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Maximum concentration (Cmax) of metabolite ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Time to maximum concentration (tmax) of metabolite ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Area under the plasma concentration-time curve (AUC(0-t)) of metabolite ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of metabolite ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Half life (t1/2) of metabolite ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 216 h post-dose after oral solution dosing
measure: Maximum concentration (Cmax) of metabolite 14C-ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Time to maximum concentration (tmax) of metabolite 14C-ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Area under the plasma concentration-time curve (AUC(0-t)) of metabolite 14C-ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of metabolite 14C-ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Half life (t1/2) of metabolite 14C-ORM 15341 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Maximum concentration (Cmax) of 14C-ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Time to maximum concentration (tmax) of 14C-ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Area under the plasma concentration-time curve (AUC(0-t)) of 14C-ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Area under the plasma concentration-time curve (AUC(0-infinity)) of 14C-ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Half life (t1/2) of 14C-ODM-201 in plasma
timeFrame: The samples were taken 72 h post-dose after IV dosing
measure: Maximum concentration (Cmax) of 14C-radioactivity in whole blood
timeFrame: The samples were taken 24 h post-dose after oral solution dosing
measure: Time to maximum concentration (tmax) of 14C-radioactivity in whole blood
timeFrame: The samples were taken 24 h post-dose after oral solution dosing
measure: Area under the plasma concentration-time curve (AUC(0-t)) of 14C-radioactivity in whole blood
timeFrame: The samples were taken 24 h post-dose after oral solution dosing
measure: Renal elimination for ODM-201 in urine
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 14 d post-dose after oral solution dosing
measure: Renal elimination for 14C-ODM-201 in urine
timeFrame: The samples were taken up-to 14 d post-dose after oral solution dosing
measure: Fraction absorbed (FA) of total radioactivity based on urinary recovery of total radioactivity for both IV and oral dosing
timeFrame: The samples were taken 72 h post-dose after IV dosing and up-to 14 d post-dose after oral solution dosing
measure: Adverse events
timeFrame: Collected 7 days post-dose in part 1 and up to 14 days post-dose in part 2
measure: Physical examination
timeFrame: Assessed at screening, pre-dose, at discharge from the study centre (72 h and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2)
measure: Blood pressure
timeFrame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose
measure: Heart rate
timeFrame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose
measure: Oral temperature
timeFrame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose
measure: 12-lead ECG
timeFrame: Assessed at screening, pre-dose, 3 h, 5 h, 12 h, 24 h, 36 h and 48 h post-dose and at discharge from the study centre (72 h post-dose in part 1 and latest at 14 d post-dose in part 2) and in addition in part 1 7 d post-dose
measure: Clinical chemistry
timeFrame: Assessed at screening, pre-dose, 24 h and 48 h post-dose and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2
measure: Haematology
timeFrame: Assessed at screening, pre-dose, 24 h and 48 h post-dose and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2
measure: Urinalysis
timeFrame: Assessed at screening, pre-dose, 24 h and 48 h post-dose and 7 d post-dose in part 1 and latest at 14 d post-dose in part 2
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Clinical
Study officials:
affiliation: Quotient Clinical
name: Philip Evans, MB ChB MRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zurth C, Nykanen P, Wilkinson G, Taavitsainen P, Vuorela A, Huang F, Reschke S, Koskinen M. Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment. Clin Pharmacokinet. 2022 Apr;61(4):565-575. doi: 10.1007/s40262-021-01078-y. Epub 2021 Dec 6.