Clinical Trials Register

Summary
EudraCT Number:	2014-004493-42
Sponsor's Protocol Code Number:	L-CP07-167
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2014-12-03
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

Expand All Collapse All

A. Protocol Information

A.2

EudraCT number

2014-004493-42

A.3

Full title of the trial

A Phase 3, Randomized, Multi-Center, Open-Label Study to Evaluate the
Efficacy and Safety of Leuprolide Acetate 11.25 and 30 mg Formulations
in Children with Central Precocious Puberty

A.3.1

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

A clinical trial to determine safety and efficacy of Leuprolide Acetate 11.25mg and 30mg in children with central premature puberty

A.4.1

Sponsor's protocol code number

L-CP07-167

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	Abbvie previously known as Abbott
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	Abbvie previously known as Abbott
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	AbbVie Ltd.
B.5.2	Functional name of contact point	EU Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Abbott House, Vanwall Business Park, Vanwall
B.5.3.2	Town/ city	Maidenhead, Berkshire
B.5.3.3	Post code	SL6 4XE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+aa1628773355
B.5.5	Fax number	+441628644330
B.5.6	E-mail	eu-clinical-trials@abbvie.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	Yes
D.2.1.1.1	Trade name	trade name depends on the source of the product
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda Pharmaceutical Company Ltd,
D.2.1.2	Country which granted the Marketing Authorisation	Japan
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 depot
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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEUPRORELIN ACETATE
D.3.9.1	CAS number	74381-53-6
D.3.9.4	EV Substance Code	SUB02900MIG
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	11.25
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.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	trade name depends on the source of the product
D.2.1.1.2	Name of the Marketing Authorisation holder	Takeda Pharmaceutical Company Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Japan
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.3.4	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	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEUPRORELIN ACETATE
D.3.9.1	CAS number	74381-53-6
D.3.9.4	EV Substance Code	SUB02900MIG
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	30
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

Central Precocious Puberty

E.1.1.1

Medical condition in easily understood language

Central Precocious Puberty

E.1.1.2

Therapeutic area

Diseases [C] - Hormonal diseases [C19]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.1
E.1.2	Level	LLT
E.1.2	Classification code	10073186
E.1.2	Term	Central precocious puberty
E.1.2	System Organ Class	100000004860

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the efficacy and safety of the 11.25 mg and 30 mg formulations of leuprolide acetate for the treatment of central precocious puberty (CPP) in children who either are naïve to previous treatment with gonadotropin-releasing hormone analog (GnRHa) or who have previously been treated with GnRHa for at least the prior 6 months.

E.2.2

Secondary objectives of the trial

To evaluate the pharmacokinetic (PK) profile of leuprolide following
intramuscular (IM) administration of the 11.25 and 30 mg depot formulations in a subset of subjects with
CPP.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. The informed consent form, assent form and any privacy statement (e.g., HIPAA)
must be approved by a local or central Institutional Review Board (IRB) as
required by State and local regulations. Prior to performing any trial-related
procedures, each subject's parent must review, understand, and sign an informed
consent form. When determined to be appropriate (as specified either by the IRB
and/or State and local regulations), each subject must also sign the assent form
after having had an opportunity to review the form and have its contents explained
and questions answered.
2. Subject has a clinical diagnosis of CPP.
3. Eligible to receive at least 6 months of therapy to treat CPP after study entry.
4. Chronological age at onset of pubertal symptoms less than 8 years old in girls and
less than 9 years old in boys at Day 1.
5. Bone age advanced at least 1 year beyond the chronological age at time of
diagnosis or first GnRHa therapy.
6. In general good health with no uncontrolled, clinically significant disease which
would interfere with bone maturation or mask the objectives of this protocol as
assessed by the investigator.
Additional criteria for subjects naïve to GnRHa treatment:
7. Girls 2-8 years inclusive or Boys 2-9 years inclusive at Day 1
8. Pretreatment pubertal response to leuprolide acetate stimulation (LH ≥ 8 mIU/mL)
at Screening.
9. Breast pubertal staging of at least II in Girls; testicular volume of at least 4cc or
testicular length greater than 2.5 cm in Boys at Screening.
Additional criteria for subjects previously treated with GnRHa:
10. Girls 2-10 years inclusive or Boys 2-11 years inclusive at Day 1.
11. Must have been on standard GnRHa therapy for at least the 6 months prior to
Day 1.
to the end of their previous GnRHa treatment cycle.
12. Should have documented maintenance of LH suppression as evidenced by peak
stimulated LH < 4 mIU/mL at Screening.

E.4

Principal exclusion criteria

1. Incomplete precocious puberty (premature thelarche, premature adrenarche).
2. Peripheral precocious puberty: gonadal or adrenal tumors, congenital adrenal
hyperplasia, testotoxicosis in boys, hCG secreting tumor or McCune-Albright
syndrome in girls.
3. Evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal
function other than premature secretion of gonadotropins not adequately
controlled.
4. Unstable intracranial tumors (unresponsive to treatment/expanding) except
hamartoma.
5. Previous treatment with GnRHa therapy requiring leuprolide acetate for depot
suspension > 15 mg monthly.
6. Bone age > 13 years for girls and > 14 years for boys.
7. Any other condition interfering with growth, i.e., skeletal dysplasia, cerebral palsy.
8. Chronic illness requiring treatment that may interfere with growth, i.e., chronic
steroid use, renal failure, moderate to severe scoliosis.
9. Diagnosis of short stature, i.e., more than 2.25 SD below the mean height for age
(growth chart measurement).
10. Prior or current therapy with medroxyprogesterone acetate.
11. Prior or current therapy with growth hormone.
12. Subject has an abnormal laboratory value that suggest a clinically significant
underlying disease or condition that may prevent the subject from entering the
study or subject with the following laboratory abnormalities: Creatinine
> 1.5 mg/dL, ALT and/or AST > 2.0 × ULN, or total bilirubin > 2.0 mg/dL with
AST/ALT elevated above normal limits.
13. Subject has a positive pregnancy test.
14. Any concomitant medical condition that, in the opinion of the investigator, may
expose a subject to an unacceptable level of safety risk or that affects subject
compliance.
15. Known hypersensitivity to study medication or its excipients.
16. Subject is a family member of the investigator, sub investigator, or study
coordinator. Family member is defined to include either a child (including step or
foster child), niece, nephew, sibling or cousin.
17. Participation in another drug research within 3 months of randomization into this
study.
18. Prior or current therapy with IGF-1.
19. Use of an estrogen preparation within 2 months prior to Day 1.

E.5 End points

E.5.1

Primary end point(s)

Suppression of LH from Month 2 through Month 6 as determined by peak stimulated
LH < 4 mIU/mL at Months 2, 3 and 6.

E.5.1.1

Timepoint(s) of evaluation of this end point

months 2,3 and 6

E.5.2

Secondary end point(s)

● Suppression of sex steroids (E2 < 20 pg/mL in girls and T < 30 ng/dL in boys)
measured at Months 1, 2, 3 and 6.
● Peak stimulated LH concentrations at Months 1, 2, 3 and 6.
● Suppression of the physical signs of puberty at Month 6 (subjects entering the
study with Pubertal staging 5 will be excluded from this analysis), defined as:
○ Regression or no progression of breast development according to Pubertal
staging (in girls).
○ Regression or no progression in testicular volume and genital staging
according to Pubertal staging (boys).
● Change from baseline in growth rate after 6-months of treatment within each
of the subgroups of subjects naïve to GnRHa treatment and previously treated.
● The ratio of change from baseline in bone age/change from baseline in
chronological age after 6 months of treatment within each of the subgroups of
subjects naïve to GnRHa treatment and previously treated.

E.5.2.1

Timepoint(s) of evaluation of this end point

months 1,2,3 and 6

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

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

Yes

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Puerto Rico

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.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

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.4.2

For a multinational trial

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)

Subjects who complete the 6-month treatment period will either enter the Follow-up
Period and resume standard of care as deemed appropriate by the treating
endocrinologist, or if eligible, will enter a separate extension study.

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials