An Open-Label, Single Dose Study Designed to Assess the Mass Balance Recovery, Metabolite Profiles and Metabolite Identification of [14C]-Estetrol in Healthy Female Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Estetrol
- Conditions
- Contraception
- Sponsor
- Estetra
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- Mass Balance of Total Radioactivity in Faeces:
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This study is being conducted to further understand the elimination pathways, metabolite profile and pharmacokinetic (PK) profile of carbon 14 labelled estetrol ([14C] estetrol).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy females of non-child bearing potential, i.e. surgically sterilised or post menopausal subjects. Postmenopausal status will be defined by an absence of menses for a minimum of 12 months and confirmed by a FSH result ≥30 IU/ml
- •Negative pregnancy test at screening and Day -1
- •30 to 65 years of age inclusive
- •Body mass index between ≥18.0 and ≤30.0 kg/m2
- •Must be willing and able to communicate and participate in the whole study
- •Must provide written informed consent
- •Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)Must agree to use an adequate method of contraception
Exclusion Criteria
- •Participation in a clinical research study within the previous 3 months
- •Subjects who are study site employees, or immediate family members of a study site or sponsor employee
- •Subjects who have previously been enrolled in this study
- •History of any drug or alcohol abuse in the past 2 years
- •Regular alcohol consumption i.e. \>14 units per week (1 unit = ½ pint beer, 25 ml of 40% spirit or a 125 ml glass of wine)
- •Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening
- •Females who are pregnant or lactating
- •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 1999, shall participate in the study
- •Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed at screening
- •Clinically significant abnormal biochemistry, haematology or urinalysis as judged by the investigator
Arms & Interventions
Estetrol
A single oral dose of 15 mg carbon 14 labelled estetrol (\[14C\]-estetrol), containing approximately 2.8 MBq (76 µCi) 14C
Intervention: Estetrol
Outcomes
Primary Outcomes
Mass Balance of Total Radioactivity in Faeces:
Time Frame: From Day -1 prior study treatment intake to 312 hours post-dose
Amount excreted in faeces (Ae\[faeces\])
Mass Balance of Total Radioactivity in Urine
Time Frame: From Day -1 prior study treatment intake to 312 hours post-dose
Amount excreted in urine (Ae\[urine\])
Secondary Outcomes
- Cmax of Total Radioactivity in Whole Blood(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(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)
- Maximum Concentration (Cmax) of Total Radioactivity in Plasma(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(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(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(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(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(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(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(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(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(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(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(From Day-1 prior study treatment intake to 240 hours post-dose)
- Renal Clearance (CLr) for Total Radioactivity(From Day-1 prior study treatment intake to 240 hours post-dose)
- The Terminal Elimination Rate Constant (Lambda-z) of Estetrol in Plasma(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)
- Number of Subjects With Adverse Events as a Measure of Safety and Tolerability(From maximum 28 days prior study treatment intake to 240 hours post-dose)