Clinical Trials Register

Summary
EudraCT Number:	2015-002590-38
Sponsor's Protocol Code Number:	17777
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:	2017-01-03
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

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2015-002590-38

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled Phase III study of darolutamide (ODM-201) versus placebo in addition to standard androgen deprivation therapy and docetaxel in patients with metastatic hormone-sensitive prostate cancer

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Darolutamide in addition to standard hormone therapy and docetaxel in metastatic hormone-sensitive prostate cancer

A.3.2

Name or abbreviated title of the trial where available

ARASENS

A.4.1

Sponsor's protocol code number

17777

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer AG
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bayer AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	-
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.6	E-mail	clinical-trials-contact@bayer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	NUBEQA 300 mg Filmtabletten
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Darolutamide 300mg film-coated tablet
D.3.2	Product code	BAY 1841788 300mg film-coated tablet
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BAY 1841788
D.3.9.1	CAS number	1297538-32-9
D.3.9.2	Current sponsor code	Darolutamide
D.3.9.3	Other descriptive name	BAY 1841788
D.3.9.4	EV Substance Code	SUB71144
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Docetaxel cell phaгm 20 mg/ml concentгate fог solution fог infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	cell phaгm GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Docetaxel cell phaгm 20 mg/ml concentгate fог solution fог infusion
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DOCETAXEL
D.3.9.3	Other descriptive name	DOCETAXEL
D.3.9.4	EV Substance Code	SUB12492MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic hormone-sensitive prostate cancer (mHSPC)

E.1.1.1

Medical condition in easily understood language

Prostate cancer which does respond to hormonal treatment

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10036909
E.1.2	Term	Prostate cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To demonstrate the superiority in overall survival of darolutamide in addition to standard androgen deprivation therapy (ADT) and docetaxel over placebo in addition to standard ADT and docetaxel

E.2.2

Secondary objectives of the trial

• Time to castration-resistant prostate cancer
• Time to initiation of subsequent antineoplastic therapy
• Symptomatic skeletal event free survival (SSE-FS)
• Time to first symptomatic skeletal event (SSE)
• Time to initiation of opioid use for ≥7 consecutive days
• Time to pain progression
• Time to worsening of physical symptoms of disease based on Functional assessment of cancer therapy / National Comprehensive Cancer Network prostate cancer symptom index 17 (NCCN-FACT FPSI-17)
• Safety

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects must meet the following criteria at the time of Screening:
1. Written informed consent.
2. Males ≥18 years of age.
3. Histologically or cytologically confirmed adenocarcinoma of prostate.
4. Metastatic disease documented either by a positive bone scan, or for soft tissue or visceral metastases, either by contrast-enhanced abdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI) scan assessed by Investigator and confirmed by central radiology review. Metastatic disease is defined as either malignant lesions in bone scan or measurable lymph nodes above the aortic bifurcation or soft tissue/visceral lesions according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Lymph nodes are measurable if the short axis diameter is ≥15 mm, soft tissue/visceral lesions are measurable if the long axis diameter is ≥10 mm.
• Subjects with regional lymph node metastases only (N1, below the aortic bifurcation) will not be eligible for the study. Only subjects with non-regional lymph node metastases (M1a) and/or bone metastases (M1b) and/or other sites of metastases with or without bone disease (M1c) will be eligible.
5. Subjects must be candidates for ADT and docetaxel therapy per Investigator’s judgment.
6. Started ADT (LHRH agonist/antagonist or orchiectomy) with or without first generation anti-androgen, but no longer than 12 weeks before randomization. For subjects receiving LHRH agonists, treatment in combination with a first generation anti-androgen for at least 4 weeks prior to randomization is recommended. First generation anti-androgen has to be stopped prior to randomization.
7. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
8. Blood counts at Screening: hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1.5x109/L, platelet count ≥100x109/L (subject must not have received any growth factor within 4 weeks or a blood transfusion within 7 days of the hematology laboratory sample obtained at Screening).
9. Screening values of serum alanine aminotransferase (ALT) and/or aspartate transaminase (AST) ≤1.5 x upper limit of normal (ULN), total bilirubin ≤ULN, creatinine ≤2.0 x ULN.
10. Sexually active male subjects must agree to use condoms as an effective barrier method and refrain from sperm donation, and/or their female partners of reproductive potential to use a method of effective birth control, during the treatment with darolutamide/placebo and for 3 months after treatment with darolutamide/placebo and 6 months after treatment with docetaxel.

E.4

Principal exclusion criteria

Subjects who meet any of the following criteria at the time of Screening will be excluded:
1. Prior treatment with:
• LHRH agonist/antagonists started more than 12 weeks before randomization
• Second-generation androgen receptor (AR) inhibitors such as enzalutamide, ARN-509, darolutamide, other
investigational AR inhibitors
• Cytochrome P 17 enzyme inhibitor such as abiraterone acetate or oral ketoconazole as antineoplastic treatment for prostate cancer
• Chemotherapy or immunotherapy for prostate cancer prior to randomization
2. Treatment with radiotherapy (external beam radiation therapy [EBRT], brachytherapy, or radiopharmaceuticals) within 2 weeks before randomization.
3. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs.
4. Contraindication to both CT and MRI contrast agent.
5. Had any of the following within 6 months before randomization: stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, congestive heart failure (New York Heart Association Class III or IV).
6. Uncontrolled hypertension as indicated by a resting systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg despite medical management.
7. Had a 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 before randomization and from which the subject has been disease-free.
8. A gastrointestinal disorder or procedure which is expected to interfere significantly with absorption of study drug.
9. An active viral hepatitis, known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need of treatment.
10. Previous (within 28 days before the start of study drug or 5 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s).
11. Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject’s participation in the study or evaluation of the study results.
12. Inability to swallow oral medications.
13. Close affiliation with the investigational site (e.g., a close relative of the Investigator, dependent person [e.g., employee or student of the investigational site]).
14. Previous assignment to treatment in this study.

E.5 End points

E.5.1

Primary end point(s)

Overall survival, defined as the time (in days) from date of randomization until death from any cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary analysis will be performed when approximately 509 deaths occur in the 2 treatment arms combined. The expected study duration for 509 deaths is approximately 70 months.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

•Time to PSA progression with serum testosterone being at castrate level <0.50 ng/mL,or the time to progression by soft tissue lesions or time to progression by bone lesions
•Time from randomization to initiation of first subsequent antineoplastic therapy for prostate cancer
•Time from randomization to the first occurrence of SSE or death from any cause
•Time from randomization to the first occurrence of SSE
•Time from date of randomization to the date of first opiate use for ≥7 consecutive days
•Interval from randomization to the first date a subject experiences a pain progression
•Interval from randomization to the first date a subject experiences an increase in physical symptoms based on the NCCN FACT FPSI 17 questionnaire.
•Refer to protocol section 10.3.3 for safety variables

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Overall survival

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

105

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Brazil

Canada

China

Israel

Japan

Korea, Republic of

Mexico

Taiwan

United States

Finland

France

Poland

Sweden

Bulgaria

Netherlands

Spain

Switzerland

Czechia

Germany

Italy

Belgium

Russian Federation

United Kingdom

E.8.7

Trial 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

LVLS
The study will end when all subjects on darolutamide treatment have
transitioned into a separate program to continue receiving
darolutamide (see protocol Section 8.2) or have discontinued the study
for any other reason, and all subjects on placebo have discontinued
treatment.
Until transition to the separate program, subjects on darolutamide
treatment will continue to follow all the protocol required procedures
and visits in the current protocol.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

650

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

650

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Verbal statement of consent can be given in the presence of impartial witness (independent of Sponsor and Investigator). To be documented by signature from informing physician and from witness.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

527

F.4.2.2

In the whole clinical trial

1300

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)

After treatment discontinuation, subjects will enter the Active Follow-up period and then the Long-term (Survival) Follow-up period. Therapy after discontinuation of treatment is detailed in section 8.2 ‘post study-therapy’ of the protocol.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-02-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-31

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-04-11

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