Clinical Trials Register

Summary
EudraCT Number:	2010-020821-41
Sponsor's Protocol Code Number:	MDV3100-03
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-12-24
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2010-020821-41

A.3

Full title of the trial

A Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety
Study of Oral MDV3100 in Chemotherapy-Na�ve Patients with Progressive Metastatic Prostate Cancer
Who Have Failed Androgen Deprivation Therapy

A.3.2

Name or abbreviated title of the trial where available

PREVAIL

A.4.1

Sponsor's protocol code number

MDV3100-03

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Medivation, 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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	MDV3100
D.3.2	Product code	MDV3100
D.3.4	Pharmaceutical form	Capsule, soft
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	915087-33-1
D.3.9.2	Current sponsor code	MDV3100
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	40
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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	Capsule, soft
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

Chemotherapy-Na�ve Patients with Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	9.1
E.1.2	Level	LLT
E.1.2	Classification code	10036909

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Co-Primary Objectives:
• To determine the benefit of MDV3100 as compared to placebo as assessed by overall survival;
• To determine the benefit of MDV3100 as compared to placebo as assessed by progression-free survival (PFS).

E.2.2

Secondary objectives of the trial

Key Secondary Objectives:
• To determine the benefit of MDV3100 as compared to placebo as assessed by time to first skeletal-related event;
• To determine the benefit of MDV3100 as compared to placebo as assessed by time to initiation of cytotoxic chemotherapy.
Other Secondary Objectives:
• To determine the benefit of MDV3100 as compared to placebo as assessed by time to prostate-specific antigen
progression;
• To evaluate quality of life using the FACT-P and the EQ-5D instruments;
• To evaluate emergence of pain relative to baseline at 3 and 6 months using the Brief Pain Inventory for
MDV3100 versus placebo;
• To determine the safety of treatment with MDV3100 as compared to placebo;
• To characterize MDV3100 exposure (e.g., Cmin);
• To collect PK data that will be combined with data from other studies in a population PK model.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Willing and able to provide informed consent;
2. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine
differentiation or small cell features;
3. Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy (i.e., surgical or
medical castration);
4. Patients who have not had a bilateral orchiectomy, must have a plan to maintain effective GnRH-analogue
therapy for the duration of the trial;
5. Serum testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the Screening visit;
6. Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks;
7. Progressive disease at study entry defined as one or more of the following three criteria that occurred while the
patient was on androgen deprivation therapy as defined in eligibility criterion #2:
• PSA progression defined by a minimum of two rising PSA levels with an interval of ≥ 1 week between each
determination. Patients who received an anti-androgen must have progression after withdrawal (≥ 4 weeks since
last flutamide or ≥ 6 weeks since last bicalutamide or nilutamide). The PSA value at the Screening visit should
be ≥ 2 μg/L (2 ng/mL);
• Soft tissue disease progression defined by RECIST 1.1;
• Bone disease progression defined by PCWG2 with two or more new lesions on bone scan;
8. Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by CT/MRI. Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible;
9. No prior cytotoxic chemotherapy for prostate cancer;
10. Asymptomatic or mildly symptomatic from prostate cancer (i.e., the score on Brief Pain Inventory – Short
Form Question #3 must be < 4);
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0–1;
12. Estimated life expectancy of ≥ 6 months;
13. Able to swallow the study drug and comply with study requirements.

E.4

Principal exclusion criteria

1. Severe concurrent disease,infection, or co-morbidity that, in the judgment of the Investigator, would make the
patient inappropriate for enrollment;
2. Known or suspected brain metastasis or active leptomeningeal disease;
3. History of another malignancy within the previous 5 years other than curatively treated non-melanomatous
skin cancer;
4. Absolute neutrophil count <1,500/μL, or platelet count <100,000/μL, or hemoglobin <5.6 mmol/L (9 g/dL) at the Screening visit (NOTE: patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic laboratory values obtained at the Screening visit);
5. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the ULN at the Screening visit;
6. Creatinine >177 μmol/L (2mg/dL) at the Screening visit;
7. Albumin <30 g/L (3.0 g/dL) at the Screening visit;
8. History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness or
transient ischemic attack within 12 months of enrollment (Day 1 visit);
9. Clinically significant cardiovascular disease including:
• Myocardial infarction within 6 months;
• Uncontrolled angina within 3 months;
• NYHA class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated
acquisition scan performed within three months results in a left ventricular ejection fraction that is ≥45%;
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes);
• History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place;
• Hypotension as indicated by systolic blood pressure <86 millimeters of mercury (mmHg) at the Screening visit;
• Bradycardia as indicated by a heart rate of <50 beats per minute on the Screening ECG;
• Uncontrolled hypertension as indicated by systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg at the Screening visit;
10. Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3
months);
11. Major surgery within 4 weeks of enrollment (Day 1 Visit);
12. Use of opiate analgesics for pain from prostate cancer within 4 weeks of enrollment (Day 1 visit);
13. Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment (Day 1 visit);
14. Radiation or radionuclide therapy for treatment of metastasis;
15. Treatment with flutamide within 4 weeks of enrollment (Day 1 visit);
16. Treatment with bicalutamide or nilutamide within 6 weeks of enrollment (Day 1 visit);
17. Treatment with 5-α reductase inhibitors (finasteride, dutasteride), estrogens, cytproterone within 4 weeks of enrollment (Day 1 visit)
18. Treatment with systemic biologic therapy for prostate cancer (other than approved bone targeted agents and
GnRH-analogue therapy) or other agents with anti-tumor activity within 4 weeks of enrollment (Day 1 visit);
19. History of prostate cancer progression on ketoconazole;
20. Prior use, or participation in a clinical trial, of an investigational agent that blocks androgen synthesis (e.g.,abiraterone acetate, TAK-700, TAK-683, TAK-448) or targets the androgen receptor (e.g., BMS 641988);
21. Participation in a previous clinical trial of MDV3100;
22. Use of an investigational agent within 4 weeks of enrollment (Day 1 visit);
23. Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease
PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone
per day within four weeks of enrollment (Day 1 visit);
For complete exclusion criteria list, refer to the protocol.

E.5 End points

E.5.1

Primary end point(s)

Efficacy:
The co-primary efficacy outcomes include:
• A comparison of overall survival between the MDV3100-treated and the placebo groups;
• A comparison of PFS between the MDV3100-treated and the placebo groups.
The key secondary efficacy outcomes include:
• A comparison of the time to first skeletal-related event between the MDV3100-treated and the placebo groups;
• A comparison of the time to initiation of cytotoxic chemotherapy between the MDV3100-treated and the
placebo groups.
Other secondary efficacy outcomes include:
• A comparison of the time to PSA progression between the MDV3100-treated and the placebo groups;
• FACT-P and EQ-5D data summarized descriptively;
• A summary of pain score at baseline, 3 months, and 6 months for the MDV3100-treated and the placebo groups.
Safety:
The safety of MDV3100 will be assessed by the frequency of serious adverse events, frequency and severity of
adverse events, frequency of study drug discontinuation due to adverse events, as well as the frequency of new
clinically significant changes in physical exam findings, vital signs, laboratory values, and ECGs.
Pharmacokinetics:
Exposure to MDV3100 and possibly its metabolites will be evaluated by analysis of Cmin data.

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

Yes

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

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Qualita` della vita

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Randomizzazione stratificata per centro, analisi statistica non stratificata

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.8.3

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

150

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

Information not present in EudraCT

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

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

Lo studio continua, per ogni paziente, nel follow-up a lungo termine. Fare riferimento alla sezione 9.5.7.13 del protocollo v.2.0 del 27 agosto 2010.

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.1.3

Elderly (>=65 years)

Yes

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

1122

F.4.2.2

In the whole clinical trial

1680

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)

Terapia standard per pazienti affetti da carcinoma della prostata progressivo metastatico.

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

2011-02-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-12-01

P. End of Trial
P.	End of Trial Status	Completed

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