NCT02718378

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Mar 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 18, 2016

Completed
12 days until next milestone

Study Start

First participant enrolled

March 1, 2016

Completed
23 days until next milestone

First Posted

Study publicly available on registry

March 24, 2016

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2017

Completed
Last Updated

February 9, 2017

Status Verified

February 1, 2017

Enrollment Period

11 months

First QC Date

February 18, 2016

Last Update Submit

February 8, 2017

Conditions

Prostatic Neoplasms

Keywords

safetypharmacokineticspharmacodynamicsrandomized

Outcome Measures

Primary Outcomes (2)

  • Number of participants with Adverse Events (AEs)

    Changes from baseline measurements considered clinically significant by the Investigator will be reported as AEs.

    28 days

  • Change from baseline in hormone levels

    The serum concentrations of Follicle Stimulating Hormone (FSH), Luteinising Hormone (LH), Estradiol (E2), total testosterone and free testosterone levels (actual values as well as percentage change from pre-dose concentration) will be listed and summarized descriptively by treatment group.

    28 days

Secondary Outcomes (9)

  • Change from baseline in haemostasis parameters

    28 days

  • Change from baseline in lipid parameters

    28 days

  • Change from baseline in glucose levels

    28 days

  • Change from baseline in bone turnover markers

    28 days

  • Change from baseline in sex-hormone binding globulin (SHBG) levels

    28 days

  • +4 more secondary outcomes

Study Arms (4)

No added active

PLACEBO COMPARATOR

placebo without estetrol

Drug: placebo

estetrol dose level 1

ACTIVE COMPARATOR

estetrol given in dose level 1

Drug: estetrol

estetrol dose level 2

ACTIVE COMPARATOR

estetrol given in dose level 2

Drug: estetrol

estetrol dose level 3

ACTIVE COMPARATOR

estetrol given in dose level 3

Drug: estetrol

Interventions

estetrolDRUG
estetrol dose level 1estetrol dose level 2estetrol dose level 3
placeboDRUG
No added active

Eligibility Criteria

Age40 Years - 70 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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:
  • weeks for oral preparations
  • 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
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

QPS Netherlands BV

Groningen, Provincie Groningen, 9713 AG, Netherlands

Location

Related Publications (3)

  • 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.

    PMID: 24932461RESULT

  • 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.

    PMID: 18464023RESULT

  • 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.

    PMID: 29931320DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Estetrol

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

EstriolEstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Tjeert Mensinga, MD, PhD

    QPS Netherlands BV

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 18, 2016

First Posted

March 24, 2016

Study Start

March 1, 2016

Primary Completion

February 1, 2017

Study Completion

February 1, 2017

Last Updated

February 9, 2017

Record last verified: 2017-02

Locations

NL(1)