Clinical Trials Register

Summary
EudraCT Number:	2016-004136-38
Sponsor's Protocol Code Number:	LEVOSOFT_2016
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-07
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2016-004136-38

A.3

Full title of the trial

PROSPECTIC, RANDOMIZED, NATIONAL MULTICENTRIC STUDY, FINALIZED TO ASSESS THE STABILITY OF TSH LEVELS IN THYROIDECTOMISED PATIENTS IN THERAPY WITH TWO FORMULATIONS OF LEVOTYROXIN (TABLETS AND SOFT-GEL)

STUDIO PROSPETTICO, RANDOMIZZATO, MULTICENTRICO NAZIONALE, FINALIZZATO A VALUTARE LA STABILITA’ DEI LIVELLI DI TSH IN PAZIENTI TIROIDECTOMIZZATI ED IN TERAPIA CON DUE FORMULAZIONI DI LEVOTIROXINA (COMPRESSA E SOFT-GEL)

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

LEVOSOFT_2016

A.4.1

Sponsor's protocol code number

LEVOSOFT_2016

A.5.4

Other Identifiers

Name:

LEVOSOFT_2016

Number:

LEVOSOFT_2016

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	AZIENDA OSPEDALIERA UNIVERSITARIA SENESE
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	IBSA Farmaceutici Italia S.r.l.
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	fondi della struttura sanitaria cod. interno25
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Azienda Ospedaliera Universitaria Senese
B.5.2	Functional name of contact point	UOC Endocrinologia
B.5.3	Address:
B.5.3.1	Street Address	Viale Bracci 16
B.5.3.2	Town/ city	Siena
B.5.3.3	Post code	53100
B.5.3.4	Country	Italy
B.5.4	Telephone number	0577585520
B.5.5	Fax number	0577586187
B.5.6	E-mail	m.g.castagna@ao-siena.toscana.it

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	TICHE - "88 MICROGRAMMI CAPSULE MOLLI" 100 CAPSULE IN BLISTER PVC-PCTFE/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	IBSA FARMACEUTICI ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Tiche
D.3.2	Product code	[042508135]
D.3.4	Pharmaceutical form	Capsule, soft
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	00179301
D.3.9.2	Current sponsor code	042508135
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	88
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	TICHE - "100 MICROGRAMMI CAPSULE MOLLI" 100 CAPSULE IN BLISTER PVC-PCTFE/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	IBSA FARMACEUTICI ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	tiche
D.3.2	Product code	[042508162]
D.3.4	Pharmaceutical form	Capsule, soft
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	00179301
D.3.9.2	Current sponsor code	042508162
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 3
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	TICHE - "75 MICROGRAMMI CAPSULE MOLLI" 100 CAPSULE IN BLISTER PVC-PCTFE/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	IBSA FARMACEUTICI ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Tiche
D.3.2	Product code	[042508109]
D.3.4	Pharmaceutical form	Capsule, soft
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	00179301
D.3.9.2	Current sponsor code	042508109
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 4
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	TICHE - "112 MICROGRAMMI CAPSULE MOLLI" 100 CAPSULE IN BLISTER PVC-PCTFE/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	IBSA FARMACEUTICI ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	tiche
D.3.2	Product code	[042508212]
D.3.4	Pharmaceutical form	Capsule, soft
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	00179301
D.3.9.2	Current sponsor code	042508198
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	112
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 5
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	TICHE - "125 MICROGRAMMI CAPSULE MOLLI" 100 CAPSULE IN BLISTER PVC-PCTFE/AL
D.2.1.1.2	Name of the Marketing Authorisation holder	IBSA FARMACEUTICI ITALIA S.R.L.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	tiche
D.3.2	Product code	[042508248]
D.3.4	Pharmaceutical form	Capsule, soft
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	00179301
D.3.9.2	Current sponsor code	042508046
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	125
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 6
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	EUTIROX - 25 MICROGRAMMI COMPRESSE 50 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BRACCO S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	eutirox
D.3.2	Product code	[024402048]
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	00179301
D.3.9.2	Current sponsor code	024402048
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 7
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	EUTIROX - 75 MICROGRAMMI COMPRESSE 50 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BRACCO S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	eutirox
D.3.2	Product code	[024402051]
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	00179301
D.3.9.2	Current sponsor code	024402051
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 8
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	EUTIROX - 100 MICROGRAMMI COMPRESSE 50 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BRACCO S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	eutirox
D.3.2	Product code	[024402137]
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	00179301
D.3.9.2	Current sponsor code	024402137
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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: 9
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	EUTIROX - 125 MICROGRAMMI COMPRESSE 50 COMPRESSE
D.2.1.1.2	Name of the Marketing Authorisation holder	BRACCO S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	eutirox
D.3.2	Product code	[024402063]
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	00179301
D.3.9.2	Current sponsor code	024402063
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	125
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

IATROGENIC HYPOTHYROIDISM IN THYROIDECTOMIZED PATIENTS

IPOTIROIDISMO IATROGENO IN PAZIENTI TIROIDECTOMIZZATI

E.1.1.1

Medical condition in easily understood language

HYPOTHYROIDISM IN THYROIDECTOMIZED PATIENTS

IPOTIROIDISMO IN PAZIENTI TIROIDECTOMIZZATI

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	20.0
E.1.2	Level	HLT
E.1.2	Classification code	10043741
E.1.2	Term	Thyroid hypofunction disorders
E.1.2	System Organ Class	100000004860

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The starting hypothesis is that the soft-gel formulation of levo-thyroxine for its different properties of
Pharmacokinetics can ensure greater stability of TSH levels compared to the tablet formulation
in time. To this end, the stability of the thyroid hormonal profile will be evaluated prospectively and randomly
in patients undergoing total thyroidectomy and in substitution therapy with levo-thyroxine in relation to the different
formulations of levothyroxine administered (tablet and soft-gel).formulations of levothyroxine administered (tablet and soft-gel)

L'ipotesi di partenza è che la formulazione soft-gel della levo-tiroxina per le sue diverse proprietà di
farmacocinetica possa garantire, rispetto alla formulazione in compresse, una maggiore stabilità dei livelli di TSH
nel tempo. A tal fine verrà valutata in maniera prospettica e randomizzata la stabilità del profilo ormonale tiroideo
in pazienti sottoposti a tiroidectomia totale ed in terapia sostitutiva con levo-tiroxina in relazione alle diverse
formulazioni di levotiroxina somministrata (compressa e soft-gel).

E.2.2

Secondary objectives of the trial

NOT PROVIDED

NON PREVISTO

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria for the study population
Patients can only be included in the study if they meet the following criteria:
Patients must be able to understand and communicate with the investigator, comply with the study's requests and provide written, signed and dated informed consent before carrying out any assessment
. Patients undergoing total thyroidectomy for benign or malignant thyroid disease in clinical remission, who do not require levothyroxine suppressive therapy, but only replacement therapy
TSH values ¿¿=0.5 mU / l and =2.5 mU / l stable for at least 2 months, in therapy with levothyroxine in tablets at the last hormonal evaluation
Age over 18 and under 70.

Inclusion criteria for the control group
Patients can only be included in the study if they meet the following criteria:
Patients must be able to understand and communicate with the investigator, comply with the study requests and provide written, signed and dated informed consent prior to the execution of each evaluation (NB: the control group subjects will be given specific information and will come subjected to informed consent).

Criteri di inclusione per la popolazione in studio
I Pazienti potranno essere inclusi nello studio solo se rispondono ai criteri di seguito riportati:
I pazienti devono essere in grado di intendere e comunicare con lo sperimentatore, ottemperare le richieste dello studio e fornire consenso informato scritto, firmato e datato prima dell’esecuzione di ogni valutazione
. Pazienti sottoposti a tiroidectomia totale per patologia benigna o maligna della tiroide in remissione clinica, che non richiedano terapia soppressiva con levotiroxina, ma solo terapia sostitutiva
Valori di TSH =0.5 mU/l e =2.5 mU/l stabili da almeno 2mesi, in terapia con levotiroxina in compresse all’ultima valutazione ormonale
Età maggiore di 18 anni e inferiore a 70 anni.

Criteri di inclusione per il gruppo di controllo
I Pazienti potranno essere inclusi nello studio solo se rispondono ai criteri di seguito riportati:
I pazienti devono essere in grado di intendere e comunicare con lo sperimentatore, ottemperare le richieste dello studio e fornire consenso informato scritto, firmato e datato prima dell’esecuzione di ogni valutazione (NB: ai soggetti del gruppo di controllo verranno fornite informazioni specifiche e verrò sottoposto consenso informato ad hoc).

E.4

Principal exclusion criteria

Exclusion criteria for the study population
Patients cannot be included in the study if only one of the following exclusion criteria is present:
Interfering drug therapy (estrogen-progestins, sucralfate, proton pump inhibitors, calcium carbonate, carbamazepine, phenytoin, phenobarbital, iron).
Malabsorption diseases (celiac disease, Chron's disease, chronic autoimmune gastritis
Patient with malignant pathology and with evidence of persistence of disease.

Exclusion criteria for the control group
Pharmacological therapy interfering on the pituitary-thyroid axis (dopamine, dobutamine, somatostatin, glucocorticoids, treatment with GH, bexarotene, metformin).
TSH values ¿¿<1.0 mU / l and> 4.0 mU / l at enrollment and during follow-up
Patient with malignant thyroid disease and / or autoimmune thyroid disease.

Criteri di esclusione per la popolazione in studio
I Pazienti non potranno essere inclusi nello studio se sarà presente anche solamente uno solo dei criteri di esclusione di seguito riportati:
Terapia farmacologia interferente (estro-progestinici, sucralfato, inibitori di pompa protonica, calcio carbonato, carbamazepina, fenitoina, fenobarbitale, ferro).
Malattie da malassorbimento (malattia celiaca, morbo di Chron, gastrite cronica autoimmune
Paziente con patologia maligna e con evidenza di persistenza di malattia.

Criteri di esclusione per il gruppo di controllo
Terapia farmacologia interferente sull’asse ipofisi-tiroide (dopamina, dobutamina, somatostatina, glucocorticoidi, trattamento con GH, bexarotene, metformina).
Valori di TSH < 1.0 mU/l e >4.0 mU/l all’arruolamento e in corso di follow-up
Paziente con patologia maligna della tiroide e/o con patologia autoimmune della tiroide.

E.5 End points

E.5.1

Primary end point(s)

To define the impact of the two different levo-thyroxine formulations on the stability of TSH in subjects with
surgical hypothyroidism in substitution therapy. The values ¿¿of TSH in each individual subject will be considered not
stable if the average difference between the different values ¿¿obtained with respect to the value of TSH at enrollment, will be above
of the critical difference for TSH. The percentage rate of patients with non-stable TSH will then be defined
each group (soft-gel and tablet formulation). In addition it will be evaluated, in the two groups of patients in therapy
with levo-thyroxine, the percentage rate of non-target TSH. This latest evaluation will allow us to define the
clinical significance of the variability of TSH levels observed.
If significant changes in TSH levels are found in the two study groups, the comparison will be performed
between subjects of the "S" Group of the Group "C", in order to verify which of the two formulations of levo-thyroxine is
able to ensure greater stability of TSH levels. The comparison will be made on the percentage rate of
patients with stable / non-stable TSH values ¿¿and the percentage rate of non-target / target patients observed in the two
groups.

Definire l'impatto delle due diverse formulazioni di levo-tiroxina sulla stabilità della TSH in soggetti con
ipotiroidismo chirurgico in terapia sostitutiva. I valori di TSH in ogni singolo soggetto verranno considerati non
stabili se la differenza media tra i diversi valori ottenuti rispetto al valore di TSH all'arruolamento, sarà al di sopra
della differenza critica per il TSH. Verrà quindi definito il tasso percentuale di pazienti con TSH non stabile in
ciascun gruppo (formulazione soft-gel e compressa). In aggiunta verrà valutato, nei due gruppi di pazienti in terapia
con levo-tiroxina, il tasso percentuale di TSH non a target. Questa ultima valutazione permetterà di definire il
significato clinico della variabilità dei livelli di TSH osservata.
Nel caso si riscontrino variazioni significative dei livelli di TSH nei due gruppi di studio, verrà eseguito il confronto
tra soggetti del Gruppo “S” del del Gruppo “C”, al fine di verificar quale tra le due formulazione di levo-tiroxina è
grado di garantire una maggiore stabilità dei livelli di TSH. Il confronto verrà effettuato sul tasso percentuale di
pazienti con valori di TSH stabili/non stabili e sul tasso percentuale di pazienti non a target/target osservato nei due
gruppi.

E.5.1.1

Timepoint(s) of evaluation of this end point

4 months

4 mesi

E.5.2

Secondary end point(s)

Changes in TSH over time will also be evaluated in the control group (patients with nodular goiter in
euthyroidism) to define the variability of TSH in subjects not under pharmacological treatment with levo-thyroxine.
A comparison will be made between the median value of variability observed in the control group and in the two
study groups in order to verify if the variations of the levels of TSH eventually observed are to be referred to
physiological variation of TSH rather than a different absorption of levo-thyroxine of the two different
formulations; Le variazioni del TSH nel tempo verranno valutate anche nel gruppo di controllo (pazienti con gozzo nodulare in
eutiroidismo) per definire la variabilità del TSH in soggetti non in trattamento farmacologico con levo-tiroxina.
Verrà effettuata una comparazione tra il valore mediano di variabilità osservato nel gruppo di controllo e nei due
gruppi di studio al fine di verificare se le variazioni dei livelli di TSH eventualmente osservate siano da riferire alla
fisiologica variazione del TSH piuttosto che ad un differente assorbimento della levo-tiroxina delle due diverse
formulazioni.

E.5.2.1

Timepoint(s) of evaluation of this end point

4 months

4 mesi

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

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

Yes

E.6.13.1

Other scope of the trial description

non-inferiority study

NON INFERIORITA'

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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.8.4.1

Number of sites anticipated in 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

Information not present in EudraCT

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

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:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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.4.1

In the member state

270

F.4.2

For a multinational trial

F.4.2.1

In the EEA

270

F.4.2.2

In the whole clinical trial

270

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)

At the end of the trial patients will proceed with the normal follow-up visits.

I pazienti arruolati nello studio, al termine della sperimentazione procederanno con le normali visite di follow up.

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

2018-07-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-05-21

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

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Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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