Clinical Trials Register

Summary
EudraCT Number:	2015-002462-24
Sponsor's Protocol Code Number:	T4drops-01
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-11-13
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

Greece - EOF

A.2

EudraCT number

2015-002462-24

A.3

Full title of the trial

Clinical study of the efficacy of liquid (drops) versus classic (tablets) formulations of Levothyroxine in replacement therapy of congenital hypothyroidism in infancy and childhood

Μελέτη της αποτελεσματικότητας της θεραπείας υποκατάστασης με θυροξίνη σε υγρή μορφή (σταγόνες) έναντι της κλασικής μορφής (δισκίων) στην αντιμετώπιση νηπίων και παιδιών με Συγγενή Υποθυρεοειδισμό

A.3.1

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

Comparison of the efficacy of levothyroxine preparations in tablet form and liquid form (drops)

Σύγκριση αποτελεσματικότητας σκευασμάτων θυροξίνης σε μορφή δισκίων και σε υγρή μορφή (σταγόνες)

A.3.2

Name or abbreviated title of the trial where available

UPH-T4DROPS-2015-01

A.4.1

Sponsor's protocol code number

T4drops-01

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	UNI-PHARMA SA
B.1.3.4	Country	Greece
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	UNI-PHARMA SA
B.4.2	Country	Greece
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Uni-Pharma SA
B.5.2	Functional name of contact point	Regulatory Affairs department
B.5.3	Address:
B.5.3.1	Street Address	14th Km National Road 1
B.5.3.2	Town/ city	Kifissia/Athens
B.5.3.3	Post code	14564
B.5.3.4	Country	Greece
B.5.4	Telephone number	302108072512374
B.5.5	Fax number	302108078907
B.5.6	E-mail	unipharma@uni-pharma.gr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	T4 tablets, any strength
D.2.1.1.2	Name of the Marketing Authorisation holder	UNI-PHARMA SA
D.2.1.2	Country which granted the Marketing Authorisation	Greece
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	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOTHYROXINE SODIUM
D.3.9.1	CAS number	55-03-8
D.3.9.4	EV Substance Code	SUB08495MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	12 to 200
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	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	T4 Oral drops, solution 100 μg/ml
D.3.4	Pharmaceutical form	Oral drops, solution
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEVOTHYROXINE SODIUM
D.3.9.1	CAS number	55-03-8
D.3.9.4	EV Substance Code	SUB08495MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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

Hypothyroidism in children.

Υποθυρεοειδισμός σε παιδιατρικούς ασθενείς.

E.1.1.1

Medical condition in easily understood language

Replacement of natural thyroid hormones in children, when thyroid gland does not produce enough.

Υποκατάσταση των ορμονών του θυρεοειδούς σε παιδιά, όταν ο θυρεοειδής αδένας δεν παράγει αρκετές.

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	18.1
E.1.2	Level	PT
E.1.2	Classification code	10021114
E.1.2	Term	Hypothyroidism
E.1.2	System Organ Class	10014698 - Endocrine disorders

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 compare the efficacy of a new levothyroxine liquid formulation (T4® Oral drops, solution 100 ug / ml) versus the classic form (T4® Tablets) in infants and children who suffer from congenital hypothyroidism, during the study. The aim is to avoid a statistical difference between the results of hormonal measurements to the respective intervals between the two groups.

Η σύγκριση της αποτελεσματικότητας ενός νέου σκευάσματος θυροξίνης σε υγρή μορφή (T4® Πόσιμες σταγόνες, διάλυμα 100μg/ml) έναντι της κλασικής μορφής (T4® Δισκία) σε νήπια και παιδιά που πάσχουν από Συγγενή Υποθυρεοειδισμό, κατά τη διάρκεια της μελέτης. Στόχος είναι να μην προκύψει στατιστική διαφορά των αποτελεσμάτων των ορμονολογικών μετρήσεων στις αντίστοιχες χρονικές στιγμές μεταξύ των δύο ομάδων.

E.2.2

Secondary objectives of the trial

• Measurement of the percentage of patients who had to increase or reduce the dose when changing from tablets to liquid form.
• Comparison of the study groups regarding the patients who had to increase or reduce the dose during treatment.

• Μέτρηση του ποσοστού των ασθενών στους οποίους χρειάστηκε να γίνει αύξηση ή μείωση της δόσης κατά την αντικατάσταση από τα δισκία στην υγρή μορφή.
• Σύγκριση των ομάδων μελέτης όσον αφορά τους ασθενείς στους οποίους χρειάστηκε να γίνει αύξηση ή μείωση της δόσης κατά τη διάρκεια της θεραπείας.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written parental informed consent.
2. Patients of both genders.
3. Patients with similar age and parents with similar socio-economic level so as the level of understanding before the consent to be the same.
4. Age of 4-8 years old.
5. Patients with diagnosed congenital hypothyroidism.
6. Patients already on replacement therapy with T4® Tablets.
7. TSH values 0.5-5 μU/mL.

1. Έγγραφη συγκατάθεση από τους γονείς.
2. Ασθενείς και των δύο φύλων.
3. Ασθενείς με ανάλογη ηλικία και γονείς με ανάλογο κοινωνικο-οικονομικό επίπεδο ώστε το επίπεδο κατανόησης της μελέτης πριν τη συγκατάθεση να είναι το ίδιο.
4. Ηλικία 4-8 ετών.
5. Ασθενείς με διαγνωσμένο συγγενή υποθυρεοειδισμό.
6. Ασθενείς οι οποίοι ήδη λαμβάνουν θεραπεία υποκατάστασης με σκεύασμα T4® Δισκία.
7. Τιμές TSH 0,5-5 μU/mL.

E.4

Principal exclusion criteria

1. Age less than 4 years, or more than 8 years.
2. Absence of a written consent from parents.
3. New patients not already receiving replacement therapy.
4. Patients not controlled regarding thyroid hormones.
5. TSH values off limits 0.5-5 μU / mL.
6. Patients receiving as replacement therapy a formulation other than T4® Tablets.
7. Insufficient compliance in patients already receiving replacement therapy, as evidenced by TSH values greater than 5 μU / mL.
8. Hyperthyroidism of any etiology.
9. Co-occurring cardiovascular diseases or other chronic diseases or syndromes.
10. Patients with adrenal insufficiency.

1. Ηλικία μικρότερη από 4 έτη ή μεγαλύτερη από 8 έτη.
2. Απουσία έγγραφης συγκατάθεσης από γονείς.
3. Νέοι ασθενείς που δε λαμβάνουν ήδη θεραπεία υποκατάστασης.
4. Ασθενείς μη ρυθμισμένοι όσον αφορά τις ορμόνες του θυρεοειδούς.
5. Τιμές TSH εκτός ορίων 0,5-5 μU/mL.
6. Ασθενείς οι οποίοι λαμβάνουν θεραπεία υποκατάστασης με σκεύασμα διαφορετικό εκτός των T4® Δισκίων.
7. Ανεπαρκής συμμόρφωση σε ασθενείς που ήδη λαμβάνουν θεραπεία υποκατάστασης, όπως προκύπτει από τιμές TSH άνω των 5 μU/mL.
8. Υπερθυρεοειδισμός οποιασδήποτε αιτιολογίας.
9. Συνυπάρχοντα καρδιαγγειακά νοσήματα ή άλλες χρόνιες νόσοι ή σύνδρομα.
10. Ασθενείς με επινεφριδιακή ανεπάρκεια.

E.5 End points

E.5.1

Primary end point(s)

To compare during the study the efficacy of a new levothyroxine liquid formulation (T4® Oral drops, solution 100μg/ml) versus the classic form (T4® Tablets) in infants and children with congenital hypothyroidism.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months from the inclusion of the last patient in the study

6 μήνες από την ένταξη του τελευταίου ασθενούς στη μελέτη

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months from the inclusion of the last patient in the study

6 μήνες από την ένταξη του τελευταίου ασθενούς στη μελέτη

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

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

Yes

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

Yes

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)

Yes

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS-Participation of 100 patients

LVLS-Με την εισαγωγή 100 ασθενών

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

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:

100

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:

100

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

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Pediatric patients

Παιδιατρικοί ασθενείς

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

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)

None

Ουδέν

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

2015-11-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-12

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

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