Trial Outcomes & Findings for Study Conducted to Further Understand the Elimination Pathways, Metabolite Profile and PK Profile of 14C-estetrol (NCT NCT02720224)

NCT ID: NCT02720224

Last Updated: 2019-02-15

Results Overview

Amount excreted in urine (Ae\[urine\])

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: From Day -1 prior study treatment intake to 312 hours post-dose
• Results posted on: 2019-02-15

Participant Flow

Participant milestones

Measure	Estetrol A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Conducted to Further Understand the Elimination Pathways, Metabolite Profile and PK Profile of 14C-estetrol

Baseline characteristics by cohort

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	57.8 years STANDARD_DEVIATION 3.5 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United Kingdom	6 participants n=5 Participants

PRIMARY outcome

Timeframe: From Day -1 prior study treatment intake to 312 hours post-dose

Population: Mass balance population - n = all subjects who took one dose of study treatment and had evaluable total radioactivity concentration (urinary and faecal) data.

Amount excreted in urine (Ae[urine])

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Mass Balance of Total Radioactivity in Urine	68.97 Cumulative percent excreted (%) Standard Deviation 7.30

PRIMARY outcome

Timeframe: From Day -1 prior study treatment intake to 312 hours post-dose

Population: Mass balance population - n = all subjects who took one dose of study treatment and had evaluable total radioactivity concentration (urinary and faecal) data.

Amount excreted in faeces (Ae[faeces])

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Mass Balance of Total Radioactivity in Faeces:	21.88 Cumulative percent excreted (%) Standard Deviation 8.29

SECONDARY outcome

Timeframe: 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

Population: Pharmacokinetic (PK) population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Maximum Concentration (Cmax) of Total Radioactivity in Plasma	231 ng/mL Geometric Coefficient of Variation 29.2

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Time to Maximum Concentration (Tmax) of Total Radioactivity in Plasma	0.25 hour Interval 0.25 to 0.5

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation. One subject was excluded from the AUC0-last calculation due to undetectable samples from 4 to 24 hours post E4 dose.

Outcome measures

Measure	Estetrol n=5 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Area Under the Curve From 0 Time to Last Measurable Concentration [AUC(0-last)] of Total Radioactivity in Plasma	561 ng*h/mL Interval 369.0 to 819.0

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
The Elapsed Time (Tlag) of Total Radioactivity in Plasma	0.0 hour Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Cmax of Estetrol in Plasma	16.6 ng/mL Geometric Coefficient of Variation 18.7

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Tmax of Estetrol in Plasma	0.25 hour Interval 0.25 to 0.5

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
AUC(0-last) of Estetrol in Plasma	90.4 ng*h/mL Geometric Coefficient of Variation 15.4

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
AUC(0-infinity) of Estetrol in Plasma	92.6 ng*h/mL Geometric Coefficient of Variation 15.2

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Tlag of Estetrol in Plasma	0.0 hour Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Half-life (t1/2) of Estetrol in Plasma	31.7 hour Geometric Coefficient of Variation 31.8

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
The Mean Residence Time (MRT) of Estetrol in Plasma	42.78 hour Geometric Coefficient of Variation 31.0

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Cmax of Total Radioactivity in Whole Blood	122 ng eq/mL Geometric Coefficient of Variation 27.6

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
The Terminal Elimination Rate Constant (Lambda-z) of Estetrol in Plasma	0.0218 1/hour Geometric Coefficient of Variation 31.8

SECONDARY outcome

Timeframe: 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

Population: PK population - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose plasma concentration for PK parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
AUC(0-last) of Total Radioactivity in Whole Blood	125 ng eq*h/mL Geometric Coefficient of Variation 51.7

SECONDARY outcome

Timeframe: From Day-1 prior study treatment intake to 240 hours post-dose

Population: PK and mass balance populations - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose samples (plasma, urinary and faecal) for PK and mass balance parameter estimation.

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Renal Clearance (CLr) for Estetrol	8.1 mL/min Geometric Coefficient of Variation 41.6

SECONDARY outcome

Timeframe: From Day-1 prior study treatment intake to 240 hours post-dose

Population: PK and mass balance populations - n = all subjects who took one dose of study treatment and had sufficient quantifiable post-dose samples (plasma, urinary and faecal) for PK and mass balance parameter estimation. One subject was excluded from the CLr analysis due to undetectable PK samples from 4 to 24 hours post E4 dose.

Outcome measures

Measure	Estetrol n=5 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Renal Clearance (CLr) for Total Radioactivity	273 mL/min Geometric Coefficient of Variation 27.0

SECONDARY outcome

Timeframe: From maximum 28 days prior study treatment intake to 240 hours post-dose

Population: Safety population - all subjects who took one dose of study treatment

Outcome measures

Measure	Estetrol n=6 Participants A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Number of Subjects With Adverse Events as a Measure of Safety and Tolerability	2 Participants

Adverse Events

Estetrol

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Estetrol n=6 participants at risk A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C Estetrol: 15 mg \[14C\]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Investigations BLOOD THYROID STIMULATING HORMONE INCREASED	16.7% 1/6 • Number of events 1 • Adverse event data were collected from screening (28 days before dosing) to Day 11 post-dose.
Infections and infestations NASOPHARYNGITIS	16.7% 1/6 • Number of events 1 • Adverse event data were collected from screening (28 days before dosing) to Day 11 post-dose.
Skin and subcutaneous tissue disorders BLISTER	16.7% 1/6 • Number of events 1 • Adverse event data were collected from screening (28 days before dosing) to Day 11 post-dose.

Additional Information

Marie Mawet

Estetra SPRL

Email: mmawet@mithra.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place