Clinical Trials Register

Summary
EudraCT Number:	2005-002880-98
Sponsor's Protocol Code Number:	CRO-04-62/GP/C/03/PRO
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2012-03-15
Trial 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

Spain - AEMPS

A.2

EudraCT number

2005-002880-98

A.3

Full title of the trial

Efficacy and safety of a new Leuprolide acetate 3.75 mg depot formulation, GP-Pharm s.a., when given as palliative treatment to prostate cancer patients

Eficacia y seguridad de una nueva formulación depot de Leuprorelina acetato 3,75 mg, GP-Pharm, S.A., como tratamiento paliativo en pacientes con cáncer de próstata

A.3.1

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

Efficacy and safety of a new Leuprolide acetate 3.75 mg depot formulation, GP-Pharm s.a., when given as palliative treatment to prostate cancer patients

Eficacia y seguridad de una nueva formulación depot de Leuprorelina acetato 3,75 mg, GP-Pharm, S.A., como tratamiento paliativo en pacientes con cáncer de próstata

A.3.2

Name or abbreviated title of the trial where available

Leuprolide 3.75 mg

A.4.1

Sponsor's protocol code number

CRO-04-62/GP/C/03/PRO

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	GP-Pharm s.a
B.1.3.4	Country	Spain
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	GP-Pharm s.a
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GP-Pharm s.a
B.5.2	Functional name of contact point	Director Medical Department
B.5.3	Address:
B.5.3.1	Street Address	P.I. Camí Ral, Isaac Peral 17
B.5.3.2	Town/ city	Gavà,Barcelona
B.5.3.3	Post code	08850
B.5.3.4	Country	Spain
B.5.4	Telephone number	3493 638 80 00
B.5.5	Fax number	3493 638 93 93
B.5.6	E-mail	jdelgadillo@gp-pharm.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	Leuprolide acetate GP Pharm
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	leuprolide acetate or leuprorelin
D.3.9.1	CAS number	74381-53-6
D.3.9.3	Other descriptive name	GnRH analogue or LHRH analogue
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	3.75
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	Yes
D.3.11.13.1	Other medicinal product type	LHRH analogue

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

Prostate cancer

Cancer de próstata

E.1.1.1

Medical condition in easily understood language

Prostate cancer

Cancer de próstata

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	10007113
E.1.2	Term	Cancer of prostate
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 determine the efficacy of the study treatment in reducing plasma testosterone below castration levels

E.2.2

Secondary objectives of the trial

Determination of serum LH, FSH and PSA concentrations; World Health Organization/Eastern Cooperative or Group (WHO/ECOG) performance status, bone pain, urinary symptoms and urinary pain after administration.

Evaluation of the safety of the new formulation based on: adverse events, local tolerability, vital signs, ECGs and clinical laboratory parameters.

Determination of plasma leuprolide levels (only 12 subjects - PK group in predefined clinical site)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Males at least 18 years of age or above, with histologically proven carcinoma of prostate, who might benefit from medical androgen deprivation therapy; life expectancy of at least 1 year; World Health Organization/Eastern Cooperative or Group (WHO/ECOG) performance status of 0, 1, or 2; adequate renal function at screening as defined by serum creatinine less than or equal to 1.6 times the ULN (upper limit of normal) for the clinical laboratory; adequate and stable hepatic function as defined by bilirubin less than or equal to 1.5 times the ULN and transaminases (i.e. SGOT, SGPT) less than or equal to 2.5 times the ULN for the clinical laboratory at screening; ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study; signed written informed consent prior to inclusion in the study.

E.4

Principal exclusion criteria

Evidence of brain metastases, spinal cord compression, evidence of severe urinary tract obstruction with threatening urinary retention and excruciating, severe pain from extensive osseous deposits in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms; testosterone levels < 1.5 ng/mL at screening; previous cancer systemic therapy such as chemotherapy, immunotherapy (e.g. antibody therapies, tumor-vaccines), biological response modifiers (e.g. cytokines) within 3 months of baseline; previous hormonal therapy for treatment of prostate cancer, such as LHRH analogues (e.g. Lupron®, Zoladex®); previous treatment with AR-receptor blockers, such as Casodex®, Fugerel®, Megace®, Androcur®; previous orchiectomy, adrenalectomy or hypophysectomy; previous prostatic surgery (e.g. radical prostatectomy, TUR-P) within 2 weeks of baseline; previous local therapy to the primary tumor with a curative attempt other than surgery (external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy) within 2 weeks of baseline; any investigational drug within 5 half-lives of its physiological action or 3 months, whichever is longer, of baseline; administration of 5-a-reductase inhibitors (Proscar®, Avodart®, Propecia®) within 3 months of baseline; OTC or alternative medical therapies which have an estrogenic or anti-androgenic effect within the 3 months of baseline; hematological parameters (RBC, total and differential WBC count, platelet count, hemoglobin, hematocrit) outside 20% of the upper or lower limits of normal (ULN, LLN) for the clinical laboratory at screening; co-existent malignancy; uncontrolled congestive heart failure, myocardial infarction or a coronary vascular procedure or significant symptomatic cardiovascular disease(s) within 6 months of baseline; resting uncontrolled hypertension or symptomatic hypotension within 3 months of baseline; venous thrombosis within 6 months of baseline; insulin-dependent diabetes mellitus; history of drug and/or alcohol abuse within 6 months of baseline; serious concomitant illness(es) or disease(s); patients receiving anticoagulants who have prothrombin and partial thromboplastin times outside of the normal range for the laboratory assays. Patients who are on anticoagulation or antiplatelet medications (e.g. dipyridamole, ticlopidine, warfarin derivatives) who are not receiving a stable dose for 3 months before baseline. Patients who are receiving warfarin-derivative anticoagulants who do not have an International Normalized Ratio (INR) in the therapeutic range for the clinical indication for which the anticoagulant has been prescribed; blood donations/losses within 2 months of baseline, apart from previous prostatic surgery patients (please note that these patients should not be included in the PK group); known hypersensitivity to GnRH, GnRH agonist, including any LHRH analogues, or any excipients of the study formulation; history of immunization within 4 weeks of baseline, flu shots within 2 weeks of baseline, anaphylaxis, skin disease which would interfere with injection site evaluation. Dermatographism will be documented at screening and followed up while on treatment.

E.5 End points

E.5.1

Primary end point(s)

To determine:

1. The proportion of patients achieving castration levels of plasma testosterone (defined as <0.5 ng/mL) 4 weeks after the 1st administration;
2. The proportion of patients maintaining castration levels of plasma testosterone from week 4 to study end;
3. The proportion of patients showing acute rises in plasma testosterone levels upon repeated dosing (the so-called ?acute-on-chronic? phenomenon).

Determinar:
1. La proporción de pacientes que alcanzan los niveles de castración (definidos como concentración de testosterona en plasma < 0,5 ng/mL) 4 semanas después de la primera administración.
2. La proporción de pacientes que mantienen los niveles de castración desde la cuarta semana hasta el final del estudio.
3. La proporción de pacientes, que después de alcanzar los niveles de castración, presentan valores de testosterona superiores a 0,5 ng/mL, desde la cuarta semana hasta el final del estudio.

E.5.1.1

Timepoint(s) of evaluation of this end point

1. 4 weeks after the 1st administration
2. from week 4 to study end
3. upon repeated dosing

1. 4 semanas después de la primera administración
2. desde la cuarta semana hasta el final del estudio
3. desde la cuarta semana hasta el final del estudio

E.5.2

Secondary end point(s)

1. Secondary efficacy end-points:
Determination of serum LH, FSH and PSA concentrations; World Health Organization/Eastern Cooperative or Group (WHO/ECOG) performance status, bone pain, urinary symptoms and urinary pain after administration.
2. Safety end-points:
Evaluation of the safety of the new formulation based on: AEs, local tolerability, vital signs, ECGs and clinical laboratory parameters.
3. Other assessments:
Evaluation of main leuprolide PK parameters in 12 subjects after administration of 3 doses.

1. Objetivos secundarios de eficacia:
Determinación de las concentraciones de LH, FSH y PSA; valoración del estado funcional del paciente (WHO/ECOG), dolor óseo, síntomas urinarios y dolor urinario después de la administración.
2. Objetivos de seguridad:
Evaluación de la seguridad basada en: efectos adversos, tolerabilidad local, signos vitales, ECGs y parámetros clínicos de laboratorio.
3. Otros objetivos:
Evaluación de los parámetros farmacocinéticos de Leuprorelina después de la administración de tres dosis en 12 pacientes.

E.5.2.1

Timepoint(s) of evaluation of this end point

through the study

durante el estudio

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

Yes

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

Information not present in EudraCT

E.8.1.2

Open

Information not present in EudraCT

E.8.1.3

Single blind

Information not present in EudraCT

E.8.1.4

Double blind

Information not present in EudraCT

E.8.1.5

Parallel group

Information not present in EudraCT

E.8.1.6

Cross over

Information not present in EudraCT

E.8.1.7

Other

Information not present in EudraCT

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

United States

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

the last visit of the last subject undergoing the trial

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

Information not present in EudraCT

F.1.1.2

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

Information not present in EudraCT

F.1.1.3

Newborns (0-27 days)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Information not present in EudraCT

F.1.1.5

Children (2-11years)

Information not present in EudraCT

F.1.1.6

Adolescents (12-17 years)

Information not present in EudraCT

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

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

120

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)

No different from the expected normal treatment of that condition

Sin diferencias respesto a la práctica clínica habitual para esta patología

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

2006-02-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2005-11-10

P. End of Trial
P.	End of Trial Status	Ongoing

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