Clinical Trials Register

Summary
EudraCT Number:	2017-001333-88
Sponsor's Protocol Code Number:	FP01C-17-001
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-07-26
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

Czechia - SUKL

A.2

EudraCT number

2017-001333-88

A.3

Full title of the trial

An Open-Label, Single-Arm Study of The Efficacy, Safety, and Pharmacokinetic Behavior of Leuprolide Mesylate Injectable Suspension (LMIS 25 mg) in Subjects with Prostate Cancer

Otevřená, jednoramenná studie bezpečnosti, účinnosti a
farmakokinetického chování leuprolid mesylátu pro injekční suspenzi
(LMIS 25 mg) u subjektů s karcinomem prostaty

A.3.1

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

A clinical trial for prostatic cancer patients . The study medication will be Leuprolide Mesylate, which will be administered as an injection twice. Both the study doctors and clinical trial participants know which treatment is being administered, there will be only one treatment group. The safety and efficacy of the medicinal product will be tested during the study.

A.4.1

Sponsor's protocol code number

FP01C-17-001

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	Foresee Pharmaceuticals Co., Ltd.
B.1.3.4	Country	Taiwan
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	Foresee Pharmaceuticals Co., Ltd.
B.4.2	Country	Taiwan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	QPS Austria GmbH
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Parkring 12
B.5.3.2	Town/ city	Grambach
B.5.3.3	Post code	8074
B.5.3.4	Country	Austria
B.5.4	Telephone number	+ 4331625 8111611
B.5.5	Fax number	+ 4331625 8111300
B.5.6	E-mail	Barbara.Derler@qps.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 Mesylate injectable suspension 25mg
D.3.2	Product code	LMIS 25 mg
D.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Leuprolide Mesylate
D.3.9.2	Current sponsor code	LMIS 25mg
D.3.9.3	Other descriptive name	LEUPROLIDE MESYLATE
D.3.9.4	EV Substance Code	SUB166604
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
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

Prostate Carcinoma

E.1.1.1

Medical condition in easily understood language

Prostate Cancer

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	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10036921
E.1.2	Term	Prostate carcinoma
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

LMIS 25 mg is the mesylate salt of leuprolide and has the same biological activity profile as leuprolide acetate salt. It is a luteinizing hormone-releasing hormone (LH-RH) agonist acting as a potent inhibitor of gonadotropin secretion when given in therapeutic doses, and lowers testosterone levels to castrate levels. Leuprolide is the standard of care for palliative treatment of prostate cancer. This study is designed to evaluate the safety, efficacy, and pharmacokinetic (PK) profile of LMIS 25 mg when given as two separate subcutaneous injections administered 12 weeks apart in subjects with prostate cancer. 1. Primary objective: To assess the efficacy and safety of LMIS 25 mg for up to 24 weeks following 2 subcutaneous doses given 12 weeks apart in subjects with prostate cancer.

E.2.2

Secondary objectives of the trial

To establish a PK profile of serum leuprolide for LMIS 25 mg in a subset of subjects with prostate cancer.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(1) Males aged ≥ 18 years old
(2) Males with histologically confirmed carcinoma of the prostate
(3) Subjects who are judged by the attending physician and/or principal investigator to be a candidate for androgen ablation therapy
(4) Baseline morning serum testosterone level > 150 ng/dL performed at screening visit
(5) Eastern Cooperative Oncology Group (ECOG) Performance score ≤ 2
(6) Life expectancy of at least 18 months
(7) Laboratory values
o Absolute neutrophil count ≥ 1,500 cells/μL
o Platelets ≥ 100,000 cells/μL
o Hemoglobin ≥ 10 gm/dL
o Total bilirubin ≤ 1.5 × upper limit of normal (ULN)
o AST (SGOT) ≤ 2.5 × ULN
o ALT (SGPT) ≤ 2.5 × ULN
o Serum creatinine ≤ 1.5 mg/dL
o Lipid profile within acceptable range according to investigator’s opinion
o Serum glucose within acceptable range according to investigator’s opinion
o HbA1c ≤ 9.5%
o Clinical chemistries (K, Na, Mg, Ca and P) within acceptable range according to Investigator’s opinion
o Normal urinalysis results within:
• RBCs ≤ 3 RBCs/hpf
• WBCs ≤ 5 WBCs/hpf
• Nitrate: negative
• Glucose: <0.1 g/dL; but <1.0 g/dL in subjects with diabetes mellitus
(8) Agree to use male contraceptive methods during study trial
(9) In the investigator’s opinion, the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the investigator and to participate in, and to comply with, the requirements of the entire protocol
(10) All aspects of the protocol explained and written informed consent obtained

E.4

Principal exclusion criteria

(1) Receipt of chemotherapy, immunotherapy, cryotherapy, radiotherapy, or anti-androgen therapy concomitantly, or within 8 weeks prior to screening visit, for treatment of carcinoma of the prostate. Radiation for pain control will be allowed during the study.
(2) Receipt of any vaccination (including influenza) within 4 weeks of screening visit
(3) History of blood donation within 2 months of screening visit
(4) History of anaphylaxis to any LH-RH analogues
(5) Receipt of any LH-RH suppressive therapy within 6 months of screening visit
(6) Patients who were previously enrolled in the LMIS 50 mg study
(7) Major surgery, including any prostatic surgery, within 4 weeks of screening visit
(8) History and concomitant clinical and radiographic evidence of central nervous system/spinal cord metastases and subjects at risk for spinal cord compression
(9) Clinical evidence of active urinary tract obstruction and subjects at risk for urinary obstruction
(10) History of bilateral orchiectomy, adrenalectomy, or hypophysectomy
(11) History or presence of hypogonadism; or receipt of exogenous testosterone supplementation within 6 months of screening visit
(12) Clinically significant abnormal ECG and/or history of clinically significant cardiovascular disease as judged by the investigator
(13) History of drug and/or alcohol abuse within 6 months of screening visit
(14) Contraindication to leuprolide or an LH-RH agonist as indicated on package labeling
(15) Use of 5-alpha reductase inhibitor within the last 6 months of screening visit
(16) History or presence of insulin-dependent diabetes mellitus (Type I). Presence of well controlled diabetes mellitus Type II will be allowed if only oral hypoglycemic are required. Prostate cancer subjects with poor controlled diabetes mellitus with Hb1Ac > 9.5% or urine glycosuria > 1.0 g/dL should be excluded.
(17) Use of systemic corticosteroids at a dose > 10 mg/d or anti-androgens
(18) Use of any investigational agent within 4 weeks of screening visit
(19) Use of any over-the-counter (OTC) medication within 4 weeks of screening visit except for those listed in the permitted Concomitant Treatment section
(20) Uncontrolled intercurrent illness that would jeopardize the subject’s safety, interfere with the objectives of the protocol, or limit the subject’s compliance with study requirements, as determined by the investigator in consultation with the sponsor

E.5 End points

E.5.1

Primary end point(s)

To determine the percentage of subjects with a serum testosterone concentration suppressed to castrate levels (≤ 50 ng/dL) on Day 28 ± 1 day (week 4) following administration of LMIS 25 mg, and the proportion of subjects with serum testosterone suppression (≤ 50 ng/dL) maintained from Day 28 ± 1 day (week 4) through Day 168 ± 5 days (week 24).

E.5.1.1

Timepoint(s) of evaluation of this end point

1. safety and tolerability Endpoints: Visits 1-23
2. Efficacy evaluation: Visits 1-23
3. Evaluation of pharmacokinetics: Visits 2-23

E.5.2

Secondary end point(s)

2.1 Efficacy:
• The mean acute-on-chronic (surge) changes in testosterone and LH levels from just prior to the second injection through 14 days after the second injection of LMIS 25 mg (Day 98, week 14) • Effect of LMIS 25 mg on serum LH levels • Effect of LMIS 25 mg on serum prostate-specific antigen (PSA) levels • The percentage of subject with PSA relapse defined as after achieving the serum PSA level ≤ 4 ng/mL post LMIS 25 mg injection but with an increase in serum PSA of >50% PSA nadir by Day 168± 5 days (week 24) • The percentage of subject achieving normal serum PSA level (<4 ng/dL) on Day 168 ± 5 days (week 24) • The percentage of subjects with enhanced serum testosterone concentration suppression to ≤ 20 ng/dL on Day 28 ± 1 day (week4) and on Day 168 ± 5 days (week 24).
2.2 Safety:
• Adverse event (AE)/ serious adverse event (SAE) reporting • Assessment of injection site reaction • Change in bone pain measurement (by Visual Analogue Scale [VAS] scale) • Change in urinary signs and symptoms and total scores assessed by the International Prostate Symptom Score (I-PSS) sheet • Change in vital signs (BP, HR, RR, weight) • Change in physical examinations with clinical significance compared to baseline by principal investigator’s judgment • Change in lab data, including liver function (AST, ALT, ALP), renal function (BUN, SCr), complete blood count with platelets, clinical chemistries (K, Na, Mg, Ca and P), urinalysis, serum glucose, lipid profile (LDL, HDL, triglycerides) and HbA1c level • Clinically significant changes in 12-lead resting electrocardiogram (ECG) per the investigator’s judgment.
2.3 Pharmacokinetic:
• The serum pharmacokinetic profile of leuprolide for up to 26 weeks following 2 subcutaneous injections of LMIS 25 mg given 12 weeks apart will be determined from baseline to Day 182 (week 26) in a subset of subjects. This subset of subjects will be followed for an additional two weeks to week 26 (Day 182) after the second injection. The PK parameters of leuprolide will be determined during the study period, including Cmax, Tmax, Cweek4, Cweek12, AUC0-4week, AUC0-12week, Cavg(0- week12) after each dose.
2.4 Exploratory:
• The PK/PD analysis (serum testosterone and leuprolide levels) in the first enrolled 30 subjects on Day 182 (week 26).

E.5.2.1

Timepoint(s) of evaluation of this end point

1. The proportion of subjects exhibiting post-suppression excursions of
serum testosterone: Visits 2-23
2. Effect of LMIS 25 mg on serum PSA levels: Visits 2-23
3. Effect of LMIS 25 mg on serum LH levels: Visits 2-23

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

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

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

Czech Republic

Korea, Republic of

Lithuania

Slovakia

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

LVLS

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

123

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

133

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)

Patients who complete the study will receive standard treatment/therapy.

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

2017-11-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-08-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-11-19

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