Study Conducted to Further Understand the Elimination Pathways, Metabolite Profile and PK Profile of 14C-estetrol
Condition: Contraception; Menopause
Intervention: Estetrol
Intervention description: 15 mg [14C]-estetrol containing approximately 2.8 MBq (76 μCi) 14C
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Female
Minimum age: 30 Years
Maximum age: 65 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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

          2. Negative pregnancy test at screening and Day -1

          3. 30 to 65 years of age inclusive

          4. Body mass index between ≥18.0 and ≤30.0 kg/m2

          5. Must be willing and able to communicate and participate in the whole study

          6. Must provide written informed consent

          7. 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:

          1. Participation in a clinical research study within the previous 3 months

          2. Subjects who are study site employees, or immediate family members of a study site or
             sponsor employee

          3. Subjects who have previously been enrolled in this study

          4. History of any drug or alcohol abuse in the past 2 years

          5. 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)

          6. Current smokers and those who have smoked within the last 12 months. A breath carbon
             monoxide reading of greater than 10 ppm at screening

          7. Females who are pregnant or lactating

          8. 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

          9. Subjects who do not have suitable veins for multiple venepunctures/cannulation as
             assessed at screening

         10. Clinically significant abnormal biochemistry, haematology or urinalysis as judged by
             the investigator

         11. Positive drugs of abuse test result

         12. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or
             human immunodeficiency virus (HIV) results

         13. History or presence of clinically significant cardiovascular, renal, hepatic, chronic
             respiratory or gastrointestinal disease as judged by the investigator

         14. Serious adverse reaction or serious hypersensitivity to any drug or the formulation
             excipients

         15. Presence or history of clinically significant allergy requiring treatment, as judged
             by the investigator. Hayfever is allowed unless it is active

         16. Donation or loss of greater than 400 ml of blood within the previous 3 months

         17. Subjects who are taking, or have taken, any prescribed medications in the 28 days
             before IMP administration (exceptions may apply on a case by case basis provided they
             are considered not to interfere with the objectives of the study as agreed by the PI
             or delegate and sponsor's medical monitor), or over-the-counter drug or herbal
             remedies in the 14 days before IMP administration. If needed (i.e. an incidental and
             limited need) ibuprofen is acceptable as analgesic treatment, but must be documented
             in the (Case Report Form) CRF. Use of paracetamol is forbidden during the entire study

         18. Subjects who are not in euthyroid condition (thyroid-stimulating hormone [TSH] and
             free thyroxine [fT4] within the normal reference range)

         19. Any history of suspected malignancy with the exception of basal cell (excluded if
             within the prior 2 years) or squamous cell (excluded if within the prior one year)
             carcinoma of the skin

         20. History or presence of prolonged QT interval corrected by Bazett's formula or any
             other clinically significant ECG abnormalities as judged by the investigator based on
             12-lead ECG readings at screening

         21. Subjects with abnormal supine blood pressure at screening: at least 2 readings of
             systolic blood pressure greater than 140 mmHg or lower than 90 mmHg, and/or diastolic
             blood pressure of more than 90 mmHg or lower than 50 mmHg after minimum intervals of 5
             min

         22. Any surgical or medical condition which might significantly alter the absorption,
             distribution, metabolism, or excretion of drugs, or which may jeopardize the subject
             in case of participation in the study. The investigator should make this determination
             in consideration of the subject's medical history and/or clinical or laboratory
             evidence of any of the following:

               -  History or symptoms of inflammatory bowel disease, gastritis, ulcers,
                  gastrointestinal or rectal bleeding,

               -  History of major gastrointestinal tract surgery (subjects who have had an
                  appendectomy are acceptable for inclusion),

               -  History or presence of pancreatic injury or pancreatitis,

               -  History or presence of impaired hepatic function,

               -  History or presence of liver disease or liver injury as indicated by abnormal
                  liver function tests such as aspartate aminotransferase (AST), alanine
                  aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase
                  (ALP), or total serum bilirubin. Any single parameter elevated ≥1.5 fold upper
                  limit of normal should be re-checked once prior to enrolment/randomisation
                  (subject who have had a cholecystectomy are acceptable for inclusion if all
                  liver/gallbladder parameters are in the normal range),

               -  History or presence of impaired renal function if considered as clinically
                  significant,

               -  Abnormal urinary constituents (e.g. albumin if considered as clinically
                  significant).

         23. Suspected or current history of gynaecological or breast pathology, including any
             abnormal Pap smear within the 3 previous years (ASCUS , ASC-H , LGSIL or worse) or
             history of abnormal mammogram within the 2 previous years

         24. Failure to satisfy the investigator of fitness to participate for any other reason