Prostatic NeoplasmsPhase 1NCT02718378
Evaluation of Safety and Efficacy of Estetrol in Healthy Men
A Phase 1 study testing estetrol in people with Prostatic Neoplasms, run by Pantarhei Oncology B.V. at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 70 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- estetrol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2016to Feb 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
QPS Netherlands BV
Groningen, Provincie Groningen, 9713 AG
About this study
Official title: 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.
- Conditions
- Prostatic Neoplasms
- Being tested
- estetrol, placebo
- Keywords
- safety, pharmacokinetics, pharmacodynamics, randomized
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
estetrolDrug
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| No added active | Placebo comparator | placebo without estetrol Receives: Drug: placebo |
| estetrol dose level 1 | Active comparator | estetrol given in dose level 1 Receives: Drug: estetrol |
| estetrol dose level 2 | Active comparator | estetrol given in dose level 2 Receives: Drug: estetrol |
| estetrol dose level 3 | Active comparator | estetrol given in dose level 3 Receives: Drug: estetrol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events (AEs)
Changes from baseline measurements considered clinically significant by the Investigator will be reported as AEs.
Measured: 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.
Measured: 28 days
Secondary outcomes (9)
Change from baseline in haemostasis parameters
The relative change in Activated Protein C (APC)-resistance, prothrombin factor 1 + 2, D-dimer, free Tissue Factor Pathway Inhibitor (TFPI), antothrombin activity, protein S activity and angiotensinogen levels and the actual change from baseline will be calculated by treatment group.
Measured: 28 days
Change from baseline in lipid parameters
The relative change in total cholesterol, triglycerides, High Density Lipoprotein (HDL) cholesterol, Low Density Lipoprotein (LDL) cholesterol, Lipoprotein A (Lp(A)) levels and the actual change from baseline will be calculated by treatment group.
Measured: 28 days
Change from baseline in glucose levels
The relative change in glucose levels and the actual change from baseline will be calculated by treatment group.
Measured: 28 days
Change from baseline in bone turnover markers
The relative change in osteocalcin, type I collagen telopeptide (CTX-1) and parathyroid hormone (PTH) and the actual change from baseline will be calculated by treatment group.
Measured: 28 days
Change from baseline in sex-hormone binding globulin (SHBG) levels
The relative change in SHBG levels and the actual change from baseline will be calculated by treatment group.
Measured: 28 days
Pharmacokinetic effect of estetrol
Area under the plasma concentration versus time curve (AUC)
Measured: 28 days
Pharmacokinetic effect of estetrol
Terminal elimination half-life (t1/2)
Measured: 28 days
Pharmacokinetic effect of estetrol
Time to reach Cmax (tmax)
Measured: 28 days
Pharmacokinetic effect of estetrol
Peak plasma concentration (Cmax)
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionFeb 2017
- Study completionFeb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pantarhei Oncology B.V.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tjeert Mensinga, MD, PhD, Principal investigator, QPS Netherlands BV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02718378
- Sponsor's protocol ID
- PR3107
- Status last verified
- Feb 2017
- First submitted
- 18 Feb 2016
- Last updated
- 9 Feb 2017
- Results posted
- No
Publications
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.
PubMed 24932461Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11 Suppl 1:47-58. doi: 10.1080/13697130802073425.
PubMed 18464023Coelingh 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.
PubMed 29931320
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02718378
- Acronym / sponsor ID
- PR3107
- Conditions
- Prostatic Neoplasms
- Keywords
- safety, pharmacokinetics, pharmacodynamics, randomized
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Pantarhei Oncology B.V.University, hospital or other
- Study start
- Mar 2016
- Primary completion
- Feb 2017 (actual)
- Study completion
- Feb 2017 (actual)
- First posted
- 24 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| No added active | Placebo comparator | Drug: placeboplacebo without estetrol |
| estetrol dose level 1 | Active comparator | Drug: estetrolestetrol given in dose level 1 |
| estetrol dose level 2 | Active comparator | Drug: estetrolestetrol given in dose level 2 |
| estetrol dose level 3 | Active comparator | Drug: estetrolestetrol given in dose level 3 |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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;
Key exclusion criteria (23 listed)
- 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:
- Contraindications for steroids or estetrol;
- Prostate hyperplasia or micturition problems that suggest the presence of prostate hyperplasia;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| estetrol | Drug | estetrol dose level 1, estetrol dose level 2, estetrol dose level 3 |
| placebo | Drug | No added active |
Primary outcome
Number of participants with Adverse Events (AEs)
Time frame: 28 days
Changes from baseline measurements considered clinically significant by the Investigator will be reported as AEs.
Change from baseline in hormone levels
Time frame: 28 days
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.
9 secondary outcomes
Change from baseline in haemostasis parameters
Time frame: 28 days
Change from baseline in lipid parameters
Time frame: 28 days
Change from baseline in glucose levels
Time frame: 28 days
Change from baseline in bone turnover markers
Time frame: 28 days
Change from baseline in sex-hormone binding globulin (SHBG) levels
Time frame: 28 days
Pharmacokinetic effect of estetrol
Time frame: 28 days
Pharmacokinetic effect of estetrol
Time frame: 28 days
Pharmacokinetic effect of estetrol
Time frame: 28 days
Pharmacokinetic effect of estetrol
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2017.
- Results publication: PubMed 24932461Phillips 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.
- Results publication: PubMed 18464023Coelingh Bennink HJ, Holinka CF, Diczfalusy E. Estetrol review: profile and potential clinical applications. Climacteric. 2008;11 Suppl 1:47-58. doi: 10.1080/13697130802073425.
- Derived from this study: PubMed 29931320Coelingh 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.
Related trials for Prostatic Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
Active, not recruitingObservational study
MRI Fusion Biopsy vs. Micro-Ultrasound Guided Biopsy
Prostate Cancer
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Recruiting
Rehabilitation and Sex Therapy to Optimize Recovery After Prostate Cancer Treatment
Prostate Cancer, Urinary Incontinence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tjeert Mensinga, MD, PhD principal investigator
QPS Netherlands BV
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing estetrol in people with Prostatic Neoplasms, run by Pantarhei Oncology B.V. at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (AEs) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02718378, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2017.