This study is being conducted to further understand the elimination pathways, metabolite profile and pharmacokinetic (PK) profile of carbon 14 labelled estetrol (\[14C\] estetrol).
This will be an open-label, non-randomised, single dose study in healthy female volunteers of non-child bearing potential. Subjects will be screened for eligibility to participate in the study up to 28 days before dosing. The study will be executed in a single group, 6 subjects will be enrolled and dosed with a single oral dose of carbon 14 labelled estetrol. Subjects will be admitted to the clinical unit on the morning prior to study drug administration (Day -1). Dosing will take place on the morning of Day 1 after an overnight fast (approximately 10 h). Subjects will be resident in the clinic up to 240 h after dosing during which plasma, blood, urine and faeces samples will be collected. It is planned that subjects will be released as a group when all subjects have achieved a mass balance cumulative recovery of \>90% or if a mean of \<1% of the dose administered has been collected in urine and faeces within 2 separate, consecutive 24 h periods. In this case, collection of all samples (blood, urine and faeces) will be stopped and the subjects will undergo discharge assessments. If this criterion has not been met by all subjects on Day 11, home collections of urine and faeces may be requested at the discretion of the investigator for individual subjects.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
6
15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Quotient Clinical
Ruddington, Nottingham, United Kingdom
Mass Balance of Total Radioactivity in Urine
Amount excreted in urine (Ae\[urine\])
Time frame: From Day -1 prior study treatment intake to 312 hours post-dose
Mass Balance of Total Radioactivity in Faeces:
Amount excreted in faeces (Ae\[faeces\])
Time frame: From Day -1 prior study treatment intake to 312 hours post-dose
Maximum Concentration (Cmax) of Total Radioactivity in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Time to Maximum Concentration (Tmax) of Total Radioactivity in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Area Under the Curve From 0 Time to Last Measurable Concentration [AUC(0-last)] of Total Radioactivity in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
The Elapsed Time (Tlag) of Total Radioactivity in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Cmax of Estetrol in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Tmax of Estetrol in Plasma
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Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
AUC(0-last) of Estetrol in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
AUC(0-infinity) of Estetrol in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Tlag of Estetrol in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Half-life (t1/2) of Estetrol in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
The Mean Residence Time (MRT) of Estetrol in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Cmax of Total Radioactivity in Whole Blood
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
The Terminal Elimination Rate Constant (Lambda-z) of Estetrol in Plasma
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
AUC(0-last) of Total Radioactivity in Whole Blood
Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-dose
Renal Clearance (CLr) for Estetrol
Time frame: From Day-1 prior study treatment intake to 240 hours post-dose
Renal Clearance (CLr) for Total Radioactivity
Time frame: From Day-1 prior study treatment intake to 240 hours post-dose
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
Time frame: From maximum 28 days prior study treatment intake to 240 hours post-dose