Clinical Trials Register

Summary
EudraCT Number:	2014-003642-26
Sponsor's Protocol Code Number:	3116001
National Competent Authority:	Latvia - SAM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-11-07
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

Latvia - SAM

A.2

EudraCT number

2014-003642-26

A.3

Full title of the trial

SAFETY AND PHARMACOKINETICS OF ODM-204 IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER (CRPC): OPEN, NONRANDOMISED, UNCONTROLLED, MULTICENTRE, DOSE ESCALATION, FIRST-IN-MAN STUDY WITH A DOSE EXPANSION

A.3.1

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

Safety and pharmacokinetics of ODM-204 in patients with metastatic castration -resistant prostate cancer: an open-label,
non - randomised, uncontrolled, multicentre, dose escalation, first-in-
man study with additional expansion phase with a dose selected in the escalation phase

A.3.2

Name or abbreviated title of the trial where available

Dualides phase 1/2 study

A.4.1

Sponsor's protocol code number

3116001

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	Orion Corporation Orion Pharma
B.1.3.4	Country	Finland
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	Orion Corporation Orion Pharma
B.4.2	Country	Finland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Orion Corporation Orion Pharma
B.5.2	Functional name of contact point	Virpi Mononen
B.5.3	Address:
B.5.3.1	Street Address	Orionintie 1
B.5.3.2	Town/ city	Espoo
B.5.3.3	Post code	FI-02200
B.5.3.4	Country	Finland
B.5.4	Telephone number	+358509663288
B.5.6	E-mail	clinicaltrials@orionpharma.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	No
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	ODM-204 50 mg
D.3.2	Product code	ODM-204 50 mg
D.3.4	Pharmaceutical form	Capsule, hard
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	ODM-204
D.3.9.2	Current sponsor code	ODM-204
D.3.9.3	Other descriptive name	ODM-204
D.3.9.4	EV Substance Code	SUB168829
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	50
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	No
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	ODM-204 100 mg
D.3.2	Product code	ODM-204 100 mg
D.3.4	Pharmaceutical form	Capsule, hard
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	ODM-204
D.3.9.2	Current sponsor code	ODM-204
D.3.9.3	Other descriptive name	ODM-204
D.3.9.4	EV Substance Code	SUB168829
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	100
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Metastatic castration resistant prostate cancer (mCRPC)

E.1.1.1

Medical condition in easily understood language

Metastatic prostate cancer, which does not 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	18.0
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.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10036916
E.1.2	Term	Prostate cancer stage D
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 evaluate safety and tolerability of ODM-204 including dose limiting
toxicities (DLTs) and the maximum tolerated dose (MTD), if possible

E.2.2

Secondary objectives of the trial

To evaluate:
- PK profile of ODM-204 and its metabolites ORM-24178, ORM-25367, ORM-26343 and possible other metabolites after a single and repeated administration in fed condition at different dose levels
- PD profile of ODM-204 (including hormone and circulating tumour cell [CTC] measurements)
- preliminary antitumour activity of ODM-204 in different populations to be studied (see section 4.1) according to the following criteria:
PSA response; response in bone and soft tissue; time on treatment;
the dose of ODM-204 for further clinical studies; long term safety and tolerability of ODM-204; time to PSA and radiological progression

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent (IC) obtained.
2. Male aged ≥ 18 years.
3. Histologically or cytologically confirmed adenocarcinoma of prostate.
4. Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl, 0.5 ng/ml, 0.5 ng/ml]) on GnRH agonist or antagonist therapy, or after bilateral orchiectomy.
Patients who have not undergone bilateral orchiectomy must continue GnRH therapy during the study.
5. Metastatic disease documented by bone scan, CT or magnetic resonance imaging (MRI).
6. Prostate cancer progression documented by one or more of the following criteria:
PSA progression defined by a minimum of 3 rising PSA levels with an interval of at least 1 week between each determination. The PSA value at the screening visit should be ≥ 2 ng/ml.
- soft tissue disease progression as defined by RECIST 1.1 criteria
- bone disease progression defined by PCWG2 criteria (2 or more new lesions on bone scan compared with prior scan).
7. ECOG performance status 0-2.
8. Estimated life expectancy of at least 3 months.
9. Blood counts at screening:
- haemoglobin ≥ 10 g/dl
- absolute neutrophil count ≥ 1500/μl (1.5x10⁹/l)
- platelet count ≥ 100,000/μl (100x10⁹/l )
The subject must not have received any growth factor or blood transfusion within 7 days of the haematology laboratory values obtained at the screening visit.
10. Liver, renal and albumin values at screening:
- ALT and AST ≤ 2.5 x ULN
- total bilirubin ≤ 1.5 x ULN (except for subjects with a diagnosis of Gilbert’s disease)
- creatinine ≤ 1.5 x ULN
- albumin > 3.0 g/dl.
11. Serum potassium ≥ 3.5 mmol/l.
12. Able to swallow study treatments and comply with study requirements.
13. Acceptable and regular bowel movements in the judgement of the investigator without any acute, subacute or chronic gastrointestinal (GI) obstruction or other GI disorder or procedure which may interfere significantly with absorption of study treatment.
14. Sexually active subjects, unless surgically sterile, must agree to use condoms and an additional effective contraception method during the study treatment and for 3 months after the end of the study treatment.
15. Patients on systemic glucocorticoids for the treatment of prostate cancer or control of symptoms must have documented PSA progression by PCWG2 criteria prior start of study treatment. Patients with confirmed PSA progression while on systemic corticosteroids
other than Prednison® are required to switch to Prednison® 5 mg (once or twice a day depending on the previous glucocorticoid dose) prior the start of study treatment, but PSA progression does not have to be reconfirmed.

E.4

Principal exclusion criteria

1. History of pituitary or adrenal dysfunction.
2. Known brain metastases.
3. Active infection or other medical condition that would make prednisone (corticosteroid) contraindicated.
4. Poorly controlled diabetes as judged by the investigator.
5. Use of systemic corticosteroid with dose greater than the equivalent 10 mg of prednisone/day within 4 weeks before the start of the study treatment.
6. Prior therapy with any investigational CYP17A1i (e.g. TAK-700, TOK-001) or any investigational second-generation AR inhibitors (e.g. ARN-509, ODM-201).
7. Depending upon patient’s prior treatment, the following apply:
- prior chemotherapy: not more than 2 prior chemotherapy treatments are allowed; chemotherapy is not allowed within 4 weeks before the start of the study treatment
- prior CYP17A1i therapy must have been stopped at minimum 4 weeks and at maximum 6 months before the start of the study treatment
- prior second-generation AR inhibitor therapy must have been stopped at minimum 4 weeks and at maximum 6 months before the start of the study treatment.
8. Use of first-generation AR inhibitor within 4 weeks (within 6 weeks for bicalutamide and nilutamide) before start of the study treatment.
9. Systemic therapy with ketoconazole, or any other azole drug (e.g. fluconazole, itraconazole) within 4 weeks before the start of the study treatment.
10. Use of estrogens, cyproterone acetate, 5-α reductase inhibitors (finasteride, dutasteride) or biologic treatment within 4 weeks before the start of the study treatment. Prior radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks before start of study treatment.
11. Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a NCI CTCAE (version 4.03) grade of ≤ 1. Chemotherapy induced alopecia and grade 2 peripheral neuropathy is allowed.
12. Initiation of an osteoclast-targeted therapy (bisphosphonate or denosumab) within 4 weeks before the start of the study treatment. Patients on a stable dose of osteoclast-targeted therapy for at least 4 weeks before the start of the study treatment can continue the
treatment during the study.
13. Participation in another interventional clinical trial and any concurrent treatment with any other investigational drug except those mentioned in exclusion criterion 7 within 4 weeks before start of the study treatment.
14. Uncontrolled hypertension
 systolic BP ≥ 160 mmHg or
 diastolic BP ≥ 95 mmHg.
Subjects with history of hypertension can be included, provided that BP is controlled by
anti-hypertensive therapy.
15. Clinically significant heart disease as judged by the investigator, e.g. congestive heart
failure New York Heart Association (NYHA) class ≥ 3, myocardial infarction, arterial
thrombotic events in the past 6 months, or unstable angina.
16. Prolonged QTc interval as evidenced by:
 history or family history of long QTc syndrome
 prolonged QT interval corrected by the Fridericia correction formula (QTcF) > 450 ms
on the centrally-read ECG at screening (2 of the measurements at screening > 450 ms).
17. Major surgery within 4 weeks before the start of the study treatment.
18. History of significant bleeding disorder unrelated to cancer, including:
 diagnosed congenital bleeding disorders (e.g. von Willebrand’s disease)
 diagnosed acquired bleeding disorder (e.g. acquired anti-factor VIII antibodies) within
1 year of screening visit
 history of GI bleeding within 6 months of the screening visit.
19. Severe or uncontrolled concurrent medical condition or psychiatric illness.
20. Serious persistent infection within 2 weeks before the start of the study treatment.
21. Known history of hepatitis B, or hepatitis C.
22. Known hypersensitivity to the prednisone or study treatment or any of its ingredients (see
section 5.1).
23. Concomitant use of prohibited CYP substrates (see Appendix 4, column “Prohibited”).

E.5 End points

E.5.1

Primary end point(s)

Achieving a maximum tolerated dose (MTD) or dose limiting toxicity (DLT).

E.5.1.1

Timepoint(s) of evaluation of this end point

MTD is the dose level at which 2 or more out of 6 subjects in a cohort experience a DLT and those subjects who have received study treatment for 28 days or who had to discontinue study treatment earlier than 28 days because of DLT.
DLT is defined as any of the following toxicities with grade:
- ≥ 3 toxicity, excluding haematological toxicities, nausea, vomiting and diarrhoea
- ≥ 3 nausea, vomiting and diarrhoea uncontrolled with antiemetic and/or antidiarrheal therapy
- ≥ 3 haematological toxicity lasting for ≥ 7 days
- ≥ 4 thrombocytopenia and neutropenia
- Other laboratory values of ≥ grade 3 which are judged clinically significant by the investigator
- any other toxicity which in the judgement of the investigator and/or sponsor is viewed as a DLT.

E.5.2

Secondary end point(s)

PK profile; hormone assessment and circulating tumour cells (CTC).
For preliminary antitumour activity a serum total PSA concentration (PSA response and progression) and soft tissue response and progression will be evaluated (chest, abdomen and pelvic CT or MRI will be performed); bone response and progression will be evaluated by a radionuclide bone scan.

E.5.2.1

Timepoint(s) of evaluation of this end point

- Serum total PSA concentration will be determined every 4 weeks until 24 weeks and every 12 weeks thereafter. In case of PSA progression a confirmatory test should be obtained 3-4 weeks later.
- Chest, abdomen and pelvic CT or MRI will be performed at screening, week 12 and every 12 weeks thereafter.
- Radionuclide bone scan will be performed at screening, week 12 and every 12 weeks thereafter, except for subjects with no bone metastasis or bone pain at week 12 the scan should be performed every 24 weeks. In case of bone progression, a confirmatory scan should be
performed in 6 weeks.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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 visit will take place 28 days after the last study treatment dose with ± 4 days visit window.

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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

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

F.4.2.2

In the whole clinical trial

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)

None

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

2015-01-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-11-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-01-21

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