Clinical Trials Register

Summary
EudraCT Number:	2007-005837-13
Sponsor's Protocol Code Number:	COU-AA-301
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2008-04-04
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

UK - MHRA

A.2

EudraCT number

2007-005837-13

A.3

Full title of the trial

A Phase 3, Randomized, Double-blind, Placebo-Controlled Study of Abiraterone Acetate (CB7630) Plus Prednisolone in Patients with Metastatic Castration-Resistant Prostate Cancer Who Have Failed Docetaxel-Based Chemotherapy

A.3.1

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

Study to determine clinical benefit and safety of abiraterone acetate and prednisolone in patients with cancer of the prostate gland who have failed chemotherapy.

A.4.1

Sponsor's protocol code number

COU-AA-301

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00638690

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	Janssen Oncology, Inc.
B.1.3.4	Country	United States
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	Janssen Oncology, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cougar Biotechnology Inc
B.5.2	Functional name of contact point	Clinical Trials Manager
B.5.3	Address:
B.5.3.1	Street Address	10990 Wilshire Blvd
B.5.3.2	Town/ city	Los Angeles
B.5.3.3	Post code	CA90024
B.5.3.4	Country	United States
B.5.4	Telephone number	13109438040
B.5.5	Fax number	13109438059

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	Abiraterone acetate
D.3.2	Product code	CB7630
D.3.4	Pharmaceutical form	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	Abiraterone acetate
D.3.9.2	Current sponsor code	CB7630
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	250
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	Prednisolone
D.2.1.1.2	Name of the Marketing Authorisation holder	TEVA UK Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Prednisolone
D.3.4	Pharmaceutical form	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	PREDNISOLONE
D.3.9.1	CAS number	50-24-8
D.3.9.4	EV Substance Code	SUB10018MIG
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	5
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: 3
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	Prednisolone
D.2.1.1.2	Name of the Marketing Authorisation holder	ratiopharm 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	Prednisolone
D.3.4	Pharmaceutical form	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	PREDNISOLONE
D.3.9.1	CAS number	50-24-8
D.3.9.4	EV Substance Code	SUB10018MIG
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	5
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 in Patients who have Failed Docetaxel-Based Chemotherapy.

E.1.1.1

Medical condition in easily understood language

Cancer of the prostate gland

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10062904
E.1.2	Term	Hormone-refractory prostate cancer
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 compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer (CRPC) who have failed one or two chemotherapy regimens, one of which contains docetaxel

E.2.2

Secondary objectives of the trial

• To further evaluate the safety profile of abiraterone acetate plus prednisolone
• To further characterize the pharmacokinetics (PK) of abiraterone acetate when administered concurrently with prednisolone
• To further explore the potential utility of circulating tumor cells (CTCs) as a surrogate for clinical benefit
• To evaluate the impact of abiraterone acetate plus prednisolone on health-related quality of life (QOL)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Each patient must meet the following criteria to be enrolled in this study.
1. Willing and able to provide written informed consent
2. Written Authorization for Use and Release of Health and Research Study Information (US sites only) or Data Protection Consent (European sites only) has been obtained.
3. Age ≥ 18 years and male
4. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology
5. At least one but not more than 2 cytotoxic chemotherapy regimens for metastatic castration-resistant prostate cancer. At least one regimen must have contained docetaxel. If docetaxel-containing chemotherapy is used more than once, this will be considered as one regimen.
6. Documented prostate cancer progression as assessed by the investigator with one of the following:
a. PSA progression according to PSAWG criteria.
(Patients on systemic glucocorticoids for the treatment of prostate cancer or control of symptoms must have documented PSA progression by PSAWG criteria prior to Cycle 1 Day 1. Patients with confirmed PSA progression while on systemic glucocorticoids other than prednisone or prednisolone are required to switch to prednisone or prednisolone 5 mg twice daily prior to Cycle 1 Day 1, but PSA progression does not have to be reconfirmed.)
b. Radiographic progression in soft tissue or bone with or without PSA progression.
7. Ongoing androgen deprivation with serum testosterone < 50 ng/dL (< 2.0nM)
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
9. Hemoglobin ≥ 9.0 g/dL independent of transfusion
10. Platelet count ≥100,000/μL
11. Serum albumin ≥ 3.0 g/dL
12. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min
13. Serum potassium ≥ 3.5 mmol/L
14. Able to swallow the study drug whole as a tablet

E.4

Principal exclusion criteria

Patients who meet any of the following criteria will be excluded from the study:
1. Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection.
2. Abnormal liver functions consisting of any of the following:
• Serum bilirubin ≥ 1.5 x ULN (except for patients with documented Gilbert’s disease)
• AST or ALT ≥ 2.5 x ULN, (for patients with known liver metastasis, AST or ALT ≤ 5 x ULN is allowed)
3. Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg)
Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy.
4. Active or symptomatic viral hepatitis or chronic liver disease
5. History of pituitary or adrenal dysfunction
6. Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline
7. Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 12 months
8. Known brain metastasis
9. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
10. Prior therapy with abiraterone acetate or other CYP17 inhibitor(s), or investigational agent(s) targeting the androgen receptor for metastatic prostate cancer.
11. Prior therapy with ketoconazole for prostate cancer
12. Surgery or local prostatic intervention within 30 days of the first dose. In addition, any clinically relevant sequelae from the surgery must have resolved prior to Cycle 1 Day 1
13. Radiotherapy, chemotherapy or immunotherapy within 30 days, or single fraction of palliative radiotherapy within 14 days of administration of Cycle 1 Day 1
14. Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a NCI CTCAE (version 3) grade of ≤ 1. Chemotherapy induced alopecia and grade 2 peripheral neuropathy is allowed.
15. Current enrollment in an investigational drug or device study or participation in such a study within 30 days of Cycle 1 Day 1.
16. Condition or situation which, in the investigator’s opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with patient’s participation in the study
17. Not willing to comply with the procedural requirements of this protocol
18. Patients who have partners of childbearing potential who are not willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is overall survival defined as the time from date of randomization to death from any cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

At Day 1 of cycles 1,2, 3, 4, 5, 6 etc of treatment (each cycle being 28 days)

E.5.2

Secondary end point(s)

• Proportion of patients achieving a PSA decline ≥ 50% according to Prostate Specific Antigen Working Group (PSAWG) criteria
• Time-to-PSA progression based on PSAWG criteria
• Progression-free survival (PFS) based on imaging studies

E.5.2.1

Timepoint(s) of evaluation of this end point

At Day 1 of cycles 4, 7 and 10 (each cycle being 28 days) and at treatment discontinuation.

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

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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)

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.3

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

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

Austria

Canada

France

Germany

Hungary

Ireland

Italy

Netherlands

Poland

Spain

United Kingdom

United States

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

See 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:

386

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

772

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

130

F.4.2

For a multinational trial

F.4.2.1

In the EEA

510

F.4.2.2

In the whole clinical trial

1158

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)

See 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

2008-04-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2008-07-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-10-01

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