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    Summary
    EudraCT Number:2013-003820-36
    Sponsor's Protocol Code Number:BAY1841788/17712
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-01-15
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2013-003820-36
    A.3Full title of the trial
    A MULTINATIONAL, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED,
    PHASE III EFFICACY AND SAFETY STUDY OF DAROLUTAMIDE (ODM-201) IN MEN WITH HIGH-RISK NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A MULTINATIONAL, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED,
    PHASE III EFFICACY AND SAFETY STUDY OF DAROLUTAMIDE (ODM-201) IN MEN WITH HIGH-RISK NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
    A.3.2Name or abbreviated title of the trial where available
    Aramis
    A.4.1Sponsor's protocol code numberBAY1841788/17712
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBayer AG
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBayer Pharma AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBayer AG
    B.5.2Functional name of contact pointBayer Clinical Trials Contact
    B.5.3 Address:
    B.5.3.1Street AddressCPT Team/Ref: "EU CTR"/Bayer AG
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code13342
    B.5.3.4CountryGermany
    B.5.6E-mailclinical-trials-contact@bayer.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDarolutamide
    D.3.2Product code BAY 1841788
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDarolutamide
    D.3.9.1CAS number 1297538-32-9
    D.3.9.2Current sponsor codeBAY 1841788
    D.3.9.3Other descriptive nameODM-201
    D.3.9.4EV Substance CodeSUB71144
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    High-risk, non-metastatic castration-resistant prostate cancer (MedDRA: hormonerefractory prostate cancer)
    E.1.1.1Medical condition in easily understood language
    Non-metastatic prostate cancer, which does not respond to hormonal treatment and at high risk for progression
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10066489
    E.1.2Term Progression of prostate cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10062904
    E.1.2Term Hormone-refractory prostate cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to demonstrate the superiority of darolutamide vs. placebo in metastasis free survival (MFS) in patients with high-risk nmCRPC
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are to demonstrate the benefit of darolutamide for:
    Overal survival (OS), time to first symptomatic skeletal related event (SSE), time to initiation of first cytotoxic chemotherapy for prostate cancer, time to pain progression and
    to characterise the safety and tolerability of darolutamide
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent (IC) obtained.
    2. Males aged > = 18 years.
    3. Histologically or cytologically confirmed adenocarcinoma of prostate without neuroendocrine differentiation or small cell features.
    4. CRPC is defined as 3 rising PSA levels after the nadir taken at least 1 week apart during ADT. If the patient has a history of antiandrogen use, the
    most recent PSA value must be obtained at least 4 weeks after antiandrogen withdrawal. See Section 6.1.1 of the Protocol for further details.
    5. Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl]) on GnRH agonist or antagonist therapy or after bilateral orchiectomy. Patients who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.
    6. PSADT of <= 10 months and PSA => 2 ng/ml at screening. See Section 6.1.1 of the Protocol for further details.
    7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
    8. Blood counts at screening: haemoglobin ≥ 9.0 g/dl, absolute neutrophil count ≥ 1500/μl (1.5x10^9/l), platelet count ≥ 100,000/μl (100x10^9/l ) (patient must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory obtained at screening).
    9. Screening values of serum alanine aminotransferase (ALT) and aspartate transaminase (AST) <=2.5 x upper limit of normal (ULN), total bilirubin <= 1.5 x ULN (except patients with a diagnosis of Gilbert’s disease), creatinine <=2.0 x ULN.
    10. Sexually active patients, unless surgically sterile, must agree to use condoms as an effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of the study treatment.
    E.4Principal exclusion criteria
    1. History of metastatic disease at any time or presence of detectable metastases by blinded central reading within 42 days prior to start of study treatment. Presence of pelvic lymph nodes < 2 cm in short axis below the aortic bifurcation is allowed. See Section 6.1.1 of the Protocol for further details.
    2. Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis due to prostate cancer.
    3. Acute toxicities of prior treatments and procedures not resolved to grade <=1 or baseline before randomisation.
    4. Prior treatment with: second generation AR inhibitors such as enzalutamide, ARN-509, darolutamide, other investigational AR inhibitors,
    CYP17 enzyme inhibitor such as abiraterone acetate, TAK-700 or
    oral ketoconazole longer than for 28 days.
    5. Use of estrogens or 5-α reductase inhibitors (finasteride, dutasteride) within 28 days before rendomisation and AR inhibitors (bicalutamide, flutamide, nilutamide, cyproterone acetate) at least 28 days before screening.
    6. Prior chemotherapy or immunotherapy for prostate cancer, except adjuvant/neoadjuvant treatment completed > 2 years before randomisation.
    7. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 28 days before randomisation.
    8. Radiation therapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 12 weeks before randomisation.
    9. Severe or uncontrolled concurrent disease, infection or co-morbidity that , in the opinion of the investigator, would make the patient inappropriate for enrolment.
    10. Treatment with an osteoclast-targeted therapy (bisphosphonate or denosumab) to prevent skeletal-related events within 12 weeks before randomisation. Patients receiving osteoclast-targeted therapy to prevent bone loss at a dose and schedule indicated for osteoporosis may continue treatment at the same dose and schedule.
    11. Known hypersensitivity to the study treatment or any of its ingredients.
    12. Major surgery within 28 days before randomisation.
    13. Any of the following within 6 months before randomisation: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft; congestive heart failure New York Heart Association (NYHA) Class III or IV.
    14. Uncontrolled hypertension as indicated by a systolic BP >=160 mmHg or diastolic BP >=100 mmHg at screening. Patients may be re-screened after adjustments of antihypertensive medications.
    15. Prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e. pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed >=5 years ago and from which the patient has been disease-free.
    16. Gastrointestinal disorder or procedure which expects to interfere significantly with absorption of study treatment.
    17. Active viral hepatitis, active human immunodeficiency virus (HIV) or chronic liver disease.
    18. Treatment with any investigational drug within 28 days before randomisation.
    19. Any condition that in the opinion of the investigator would impair the patients’ ability to comply with the study procedures.
    20. Unable to swallow study medications and comply with study requirements.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy variable is metastasis free survival (MFS), defined as time between randomisation and evidence of metastasis or death from any cause, whichever occurs first
    E.5.1.1Timepoint(s) of evaluation of this end point
    Will be evaluated at about 385 events
    E.5.2Secondary end point(s)
    Overal survival (OS) is defined as time from randomisation to date of death from any cause. Survival status will be assessed from randomisation until the end of follow-up period.
    Time to first Symptomatic Skeletal Event (SSE) is defined as time from randomisation to the first occurrence of SSE. SSE is defined as External Beam Radiation Therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone
    fracture, or occurrence of spinal cord compression or tumour-related orthopaedic surgical intervention, whichever comes first.
    Time to cytotoxic chemotherapy is defined as time from randomisation to initiation of the first cytotoxic chemotherapy.
    Pain progression is defined as an increase of 2 points from baseline in question 3 of Brief Pain Inventory - Short Form (BPI-SF) (related to the worst pain in the last 24 hours) taken as a 7-day average, or initiation of short or long-acting opioids for pain, whichever comes first.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Survival status will be assessed from randomisation until the end of follow-up period.
    SSE will be assessed from randomisation until the first occurrence of SSE.
    Use of cytotoxic chemotherapy will be assessed from randomisation until the first use of cytotoxic chemotherapy.
    Pain will be assessed with the BPI-SF questionnaire (Appendix 4 to protocol), pain diary and opioid use from baseline until the end of follow-up period.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned16
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA305
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Austria
    Belarus
    Belgium
    Brazil
    Bulgaria
    Canada
    Colombia
    Czech Republic
    Estonia
    Finland
    France
    Germany
    Hungary
    Israel
    Italy
    Japan
    Korea, Republic of
    Latvia
    Lithuania
    Peru
    Poland
    Portugal
    Romania
    Russian Federation
    Serbia
    Slovakia
    South Africa
    Spain
    Sweden
    Taiwan
    Turkey
    Ukraine
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End-of-study (EOS) is when the last subject's last contact is estimated to take place. A decision to continue the study beyond the time covered by the study protocol must be based on a mutual agreement between the investigator and the sponsor.
    Premature study termination is anticipated for valid scientific/administrative reasons.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days14
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 300
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1200
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state69
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1021
    F.4.2.2In the whole clinical trial 1500
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Patient withdrawn from the study will be treated with standard of care at the discretion of the investigator.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-02-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2021-06-14
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