evaluation of safety and efficacy of estetrol in healthy men

Conditions: Prostatic Neoplasms

Summary: 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.


Eligibility criteria:
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.

Keywords: safety pharmacokinetics pharmacodynamics randomized