Evaluation of Safety and Efficacy of Estetrol in Healthy Men

A Phase I, Double-blind, Randomised, Placebo-controlled, Multiple Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Multiple Dosages of Estetrol in Healthy Men

The current study is designed as a phase Ib multiple dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of E4 in healthy men after daily oral administration for 28 days.

Inclusion Criteria:

• Male, age between 40 and 70 years (both inclusive);
• Good physical and mental health as judged by the Investigator determined by medical history, physical examination (including prostate palpation), clinical laboratory, vital signs and ECG recording;
• Body mass index between ≥ 18.5 and ≤ 30.0 kg/m2;
• Normal prostate-specific antigen (PSA) value (< 3.0 ng/mL);
• Non-vasectomized men must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study medication. Men who have been vasectomized less than 4 months prior to study start must follow the same restrictions as non-vasectomized men;
• Men must agree not to donate sperm from the first dose until 90 days after the last dose;
• Ability to communicate well with the Investigator and to comply with the requirements of the entire study;
• Willing to give informed consent in writing.

Exclusion Criteria:

• Any clinically significant abnormality following review of medical history, laboratory results, physical examination and ECG at screening as judged by the Investigator;

• Conditions or disorders that might affect the absorption, distribution, metabolism or excretion of any of the study drugs;

• Previous use of steroids within:

  • 8 weeks for oral preparations
  • 4 weeks for transdermal preparations
  • Any time for injections;

• Contraindications for steroids or estetrol;

• Prostate hyperplasia or micturition problems that suggest the presence of prostate hyperplasia;

• Presence of an active acute or chronic infection, including syphilis, HIV or viral hepatitis B and/or C (or previously treated);

• Treatment for any major psychiatric disorder in the previous 12 months or use of antidepressant medication before screening;

• Hypersensitivity to the active substances or to any of the excipients of the investigational product or placebo therapy;

• Use of probiotics (as present in dairy products, fortified foods etc.) during the 3 months before screening and during the clinical study;

• Use of one or more of the following medications:

  • Antihypertensive drugs
  • Present use or use within 30 days before the start of the study drug of the following drugs: aprepitant, bosentan, armodafinil, phenytoin, barbiturates, primidone, carbamazepine, oxcarbazepine, glucocorticoids, topiramate, felbamate, rifampicin, clobazamechinacea; vemurafenib, non-nucleoside reverse transcriptase inhibitors, griseofulvin, ketoconazole, and herbal remedies containing Hypericum perforatum
  • Any medication (including over-the-counter products) within 14 days before first dosing except for occasional non-steroidal anti-inflammatory drugs (NSAIDs; e.g. ibuprofen); paracetamol is not permitted
  • Use of antibiotics;

• Administration of any other investigational drug within 3 months before first dosing;

• Loss of more than 400 mL blood during the 3 months before screening, e.g. as a blood donor, or intention to donate blood in the 3 months after completing the study;

• Subjects with a history of (within 12 months) alcohol or drug abuse or with a positive result at screening, for tests of:

  • alcohol intake
  • drug abuse;

• Currently smoking or smoked within the last 6 months before screening.