Clinical Trials Register

Summary
EudraCT Number:	2014-004494-16
Sponsor's Protocol Code Number:	L-CP07-177
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

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A. Protocol Information

A.2

EudraCT number

2014-004494-16

A.3

Full title of the trial

A 36 Month, Multi-Center, Open-Label Extension Study to Evaluate the
Safety of Leuprolide Acetate 11.25 mg 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-CP07-177

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	+441628773355
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.3.4	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

“The objective of this study was to assess the long-term safety of continued treatment with 11.25 mg and 30 mg 3M depot formulations of leuprolide acetate over 36 months of treatment in children with CPP. This included the maintenance of LH suppression and the effects on pubertal symptoms, sex steroid levels, and bone age.”

E.2.2

Secondary objectives of the trial

Maintenance of LH suppression and the effects on pubertal symptoms, sex steroid levels and bone age.

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 Regional, 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 completed the Treatment Period of the lead-in study, L-CP07-167, and has
documented LH suppression as evidenced by peak-stimulated LH < 4 mIU/mL at
the Month 6 study visit of the lead-in study. (Note: Subjects who were enrolled
and administered the Day 1 injection in this study and are subsequently found to
not be suppressed at Month 6 of the lead-in study, will no longer be eligible to
receive future injections of investigational product and will be prematurely
discontinued from the study.
3. Demonstrated suppression of the physical signs of puberty at Month 6 of the
lead-in study (defined as regression or no progression of breast development
according to Pubertal staging (in girls) or regression or no progression in testicular
volume and genital staging according to Pubertal staging (in boys).
4. Subject is expected to receive at least 12 months of therapy to treat CPP after study
entry.
5. 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.

E.4

Principal exclusion criteria

1. Diagnosis of incomplete precocious puberty, peripheral precocious puberty, or
evidence of any abnormal pituitary, hypothalamic, adrenal, thyroid and gonadal
function other than premature secretion of gonadotropins not adequately
controlled, unstable intracranial tumors (unresponsive to treatment/expanding)
except hamartoma.
2. Bone age ≥ 14.00 years for girls and ≥ 15.00 years for boys (based on the Month 6
lead-in study, L-CP07-167, radiographic results).
3. Subject has an abnormal laboratory value that suggests 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.
4. Chronic illness requiring treatment that may interfere with growth, i.e., chronic
steroid use, renal failure, moderate to severe scoliosis.
5. Current therapy with medroxyprogesterone acetate.
6. Current therapy with growth hormone.
7. Current therapy with insulin-like growth factor-1 (IGF-1).
8. Current use of an estrogen preparation.
9. 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.
10. Subject has a positive pregnancy test.

E.5 End points

E.5.1

Primary end point(s)

There are no primary or secondary efficacy endpoints in this safety extension study.
The following maintenance of suppression endpoints will be summarized for all subjects
in each treatment group (11.25 mg leuprolide acetate or 30 mg leuprolide acetate).
Baseline refers to the last measurement prior to the first injection in the lead-in study,
L-CP07-167.
● Suppression of LH as determined by peak stimulated LH < 4 mIU/mL
measured at Day 1, Month 6, 12, 24 and 36.
● Suppression of basal sex steroids (E2 < 20 pg/mL in girls and T < 30 ng/dL in
boys) measured at Day 1, Months 3, 6, 9, 12, 18, 24, 30 and 36.
● Peak stimulated LH concentrations at Day 1, Months 6, 12, 24 and 36.
● Suppression of the physical signs of puberty at Day 1, Months 3, 6, 9, 12, 18,
24, 30 and 36 (subjects entering Study L-CP07-167 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 at Day 1, Months 6, 12, 18, 24, 30 and
36 within each of the subgroups of subjects naïve to GnRHa treatment at
baseline and previously treated.
● The ratio of change from baseline in bone age/change from baseline in
chronological age at Day 1, Months 12, 24 and 36 within each of the
subgroups of subjects naïve to GnRHa treatment at baseline and previously
treated.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 1, Months 6, 12, 18, 24, 30

E.5.2

Secondary end point(s)

• There are no secondary efficacy endpoints in this safety extension study, see endpoints listed above

E.5.2.1

Timepoint(s) of evaluation of this end point

• There are no secondary efficacy endpoints in this safety extension study, see endpoints listed above

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

E.6.6

Pharmacokinetic

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

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

LPLV

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)

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 36 month treatment period will enter the Safety Follow-Up
Period and be provided Lupron Depot PED monthly from the end of treatment visit at
Month 36 through their scheduled Week 12 F/U Visit, as deemed appropriate by the
treating endocrinologist.

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

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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:
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