Evaluation of Safety and Efficacy of Estetrol in Healthy Men

NCT ID: NCT02718378

Last Updated: 2017-02-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2017-02-28

Brief 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.

Conditions

Prostatic Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

No added active

placebo without estetrol

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

estetrol dose level 1

estetrol given in dose level 1

Group Type: ACTIVE_COMPARATOR

estetrol

Intervention Type: DRUG

estetrol dose level 2

estetrol given in dose level 2

Group Type: ACTIVE_COMPARATOR

estetrol

Intervention Type: DRUG

estetrol dose level 3

estetrol given in dose level 3

Group Type: ACTIVE_COMPARATOR

estetrol

Intervention Type: DRUG

Interventions

estetrol

Intervention Type: DRUG

placebo

Intervention Type: DRUG

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Pantarhei Oncology B.V.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tjeert Mensinga, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

QPS Netherlands BV

Locations

QPS Netherlands BV

Groningen, Provincie Groningen, Netherlands

Countries

Netherlands

References

Phillips I, Shah SI, Duong T, Abel P, Langley RE. Androgen Deprivation Therapy and the Re-emergence of Parenteral Estrogen in Prostate Cancer. Oncol Hematol Rev. 2014 Spring;10(1):42-47. doi: 10.17925/ohr.2014.10.1.42.

Reference Type: RESULT

PMID: 24932461 (View on PubMed)

Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11 Suppl 1:47-58. doi: 10.1080/13697130802073425.

Reference Type: RESULT

PMID: 18464023 (View on PubMed)

Coelingh Bennink HJT, Zimmerman Y, Verhoeven C, Dutman AE, Mensinga T, Kluft C, Reisman Y, Debruyne FMJ. A Dose-Escalating Study With the Fetal Estrogen Estetrol in Healthy Men. J Clin Endocrinol Metab. 2018 Sep 1;103(9):3239-3249. doi: 10.1210/jc.2018-00147.

Reference Type: DERIVED

PMID: 29931320 (View on PubMed)

Other Identifiers

PR3107

Identifier Type: -

Identifier Source: org_study_id