Clinical Trials Register

Summary
EudraCT Number:	2015-001832-39
Sponsor's Protocol Code Number:	LPS14060
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-09-11
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

Spain - AEMPS

A.2

EudraCT number

2015-001832-39

A.3

Full title of the trial

A twenty-six week, randomized, open-label, 2-arm parallel group real world pragmatic trial to assess the clinical and health outcomes benefit of transition to Toujeo compared to standard of care insulin, in basal insulin treated patients with uncontrolled type 2 diabetes mellitus, with six month extension.

Ensayo mundo real pragmático, de 26 semanas con 6 meses de extensión, aleatorizado, abierto, de 2 brazos paralelos, para evaluar los resultados de los beneficios clínicos y de salud de la transición a Toujeo® en comparación a las insulinas de tratamiento estándar, en pacientes con Diabetes Mellitus Tipo 2 inadecuadamente controlada tratados con insulina basal

A.3.1

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

A ?Real World? Trial to determine efficacy and health outcomes of TOUJEO compared to ?standard of care? basal insulin in patients already using basal insulin.

Ensayo "mundo real" para detarminar la eficacia y los resultados de salud de Toujeo® en comparación con las insulinas del tratamiento basal estándar en pacientes ya tratados con insulina basal

A.3.2

Name or abbreviated title of the trial where available

REGAIN CONTROL

A.4.1

Sponsor's protocol code number

LPS14060

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	sanofi-aventis Groupe
B.1.3.4	Country	France
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	sanofi-aventis Groupe
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	sanofi-aventis, s.a.
B.5.2	Functional name of contact point	Unidad Estudios Clínicos
B.5.3	Address:
B.5.3.1	Street Address	c/ Josep Pla nº2, 4ª planta
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08019
B.5.3.4	Country	Spain
B.5.4	Telephone number	93 485 94 00
B.5.6	E-mail	ES-unidadestudiosclinicos@sanofi.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	Toujeo
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis Deutschland GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Insulin glargine
D.3.2	Product code	HOE901 - U300
D.3.4	Pharmaceutical form	Solution for injection in pre-filled pen
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	INSULIN GLARGINE
D.3.9.1	CAS number	160337-95-1
D.3.9.2	Current sponsor code	HOE901 - U300
D.3.9.4	EV Substance Code	SUB08196MIG
D.3.10	Strength
D.3.10.1	Concentration unit	U/ml unit(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	300
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	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.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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

Type 2 diabetes mellitus

Diabetes Mellitus Tipo 2

E.1.1.1

Medical condition in easily understood language

Type 2 diabetes mellitus

Diabetes Mellitus Tipo 2

E.1.1.2

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	PT
E.1.2	Classification code	10067585
E.1.2	Term	Type 2 diabetes mellitus
E.1.2	System Organ Class	10027433 - Metabolism and nutrition 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 demonstrate non-inferiority of Toujeo versus ?standard of care? basal insulin therapy as measured by glycated hemoglobin (HbA1c) change.

Demostrar la no inferioridad de Toujeo frente a un tratamiento con insulina basal ?de referencia?, determinada en función del cambio en la HbA1c entre el momento basal y el Mes 6.

E.2.2

Secondary objectives of the trial

? To demonstrate superiority of Toujeo versus ?standard of care? basal insulin if non-inferiority criterion is met, measured by HbA1c change.
? To compare Toujeo to other "standard of care" basal insulin in terms of patient persistence with assigned basal insulin therapy with or without intensification.
? Risk of hypoglycemia including documented, symptomatic hypoglycemia (?70 mg/dL) or severe (according to ADA Working Group).
? Change in fasting plasma glucose (FPG).
? Change in body weight.
? Differences in patient reported outcomes measured by Diabetes Treatment Satisfaction Questionnaire Status and Change versions (DTSQs and DTSQc).
? Change in hypoglycemia control subscale of Treatment Satisfaction Questionnaire (TSQ).
? Healthcare resource utilization including hospitalizations and emergency department or other health care provider visits and healthcare costs.

Superioridad de Toujeo frente a una insulina basal ?de referencia? si se cumple el criterio de no inferioridad, determinada en función del cambio en la HbA1c entre el momento basal y el Mes 6;
Persistencia del paciente con el tratamiento asignado de insulina basal durante todo el periodo, es decir, desde el inicio hasta el final del ensayo con o sin intensificación;
Riesgo de hipoglucemia, incluida la hipoglucemia documentada sintomática (? 70 mg/dl) o severa
Cambio en la HbA1c en el Mes 12;
Cambio en la glucosa plasmática en ayunas (GPA);
Cambio en el peso corporal;
Diferencias en los resultados notificados por el paciente (PRO) medidos a través de las versiones de Estado y Cambio (DTSQs y DTSQc);
Cambio en la subescala del control Hipoglucémico en el Cuestionario sobre la Satisfacción con el Tratamiento;
Utilización de recursos sanitarios, incluidas las hospitalizaciones y las visitas a urgencias o a otro profesional sanitario y los costes sanitarios.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

? Patients with type 2 diabetes insufficiently controlled (HbA1c >7%) with current (? 6 months) ?standard of care? basal insulin therapy (including Lantus insulin glargine U100, Levemir, NPH or Tresiba or new basal insulin products including biosimilar) with or without oral agents (metformin, sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT-2 inhibitor, glinides) and with or without use of a GLP-1 receptor agonist,
? Fasting plasma glucose (FPG) >130 mg/dL (7.2 mmol/L),
? Adult patients who have signed an Informed Consent Form (ICF) and privacy form(s).

? Se incluirá en este estudio a pacientes con diabetes de tipo 2 controlada de manera insuficiente (hemoglobina glucosilada [HbA1c] >7 %) que sigan (? 6 meses) un tratamiento ?de referencia? con insulina basal (entre las que se incluyen la insulina glargina U100 Lantus, Levemir, PNH, Tresiba u otros productos de insulina basal nuevos, inclusive las biosimilares) con o sin fármacos orales (metformina, SU, tiazolidinedionas, inhibidores de la DPP-4, inhibidores del SGLT-2, glinidas) y con o sin agonistas del receptor del GLP-1;
? Glucosa plasmática en ayunas (GPA) > 130 mg/dl (7,2 mmol/l);
? Pacientes adultos que hayan firmado un Consentimiento Informado.

E.4

Principal exclusion criteria

? HbA1c ?7%, no upper bound,
? Age <18 years,
? Type 1 diabetes mellitus,
? Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening, or any major systemic disease resulting in short life expectancy that in the opinion of the Investigator would restrict or limit the patient?s successful participation for the duration of the study,
? Use of any product containing short or rapid acting insulin since the time of diagnosis with type 2 diabetes mellitus other than temporary use during a pregnancy or hospitalization, (such as Humulin®-R, , Humalog®, Novolog®, Apidra®, Afrezza®, pre-mix insulin and including biosimilar preparation of these products, or other rapid acting insulins which may become available.)
? Use of any product containing short or rapid acting insulin occurring within 3 months prior to the time of screening, such as Humulin-R, Humalog, Novolog, Apidra, Afrezza, pre-mix insulin and including biosimilar preparations of these products, or other rapid acting insulins which may become available.)
? Use of oral hypoglycemic agents other than those noted in the inclusion criteria, GLP-1 receptor agonists not approved for use with insulin, or any investigational agent (drug, biologic, device) within 3 months prior to the time of screening.
? All contraindications to ?standard of care? insulin therapy or warnings/precautions of use as displayed in the respective National Product labeling for these products.
? Pregnancy or lactation,
? Women of childbearing potential with no effective contraceptive method.

Criterios de exclusión relacionados con el diseño del estudio

? HbA1c ? 7 %, sin límitesuperior;
? Edad < 18 años;
? Diabetes mellitus de tipo 1;
? Cualquier anomalía clínicamente significativa detectada en la exploración física, las pruebas analíticas o las constantes vitales en el momento de la selección, o cualquier enfermedad sistémica importante que dé lugar a una esperanza de vida corta y que, a juicio del Investigador, pueda restringir o limitar la participación satisfactoria del paciente a lo largo del estudio;
? Uso de cualquier producto que contenga insulina de acción corta o rápida desde el momento del diagnóstico de DMT2 que no haya sido para un uso temporal durante un embarazo u hospitalización (como Humulin®-R, Humalog®, Novolog®, Apidra®, Afrezza®, insulina premezclada y productos biosimilares inclusive, o bien otras insulinas de acción rápida que puedan aparecer en el mercado);
? Uso de cualquier producto que contenga insulina de acción corta o rápida durante los 3 meses previos al momento de la selección, como Humulin-R, Humalog, Novolog, Apidra, Afrezza, insulina premezclada y preparaciones biosimilares de estos productos, o bien otras insulinas de acción rápida que puedan aparecer en el mercado;
? Uso de hipoglucemiantes orales distintos de los indicados entre los criterios de inclusión, agonistas del receptor del GLP-1 no aprobados para su uso con insulina, o cualquier producto en investigación (farmacológico, biológico o dispositivo) durante los 3 meses previos al momento de la selección.

Criterios de exclusión relacionados con el comparador activo y/o los tratamientos de base obligatorios

? Todas las contraindicaciones de los tratamientos de insulina ?de referencia? o las advertencias o precauciones de uso que aparezcan en la ficha técnica nacional de los productos correspondientes.

Criterios de exclusión relacionados con el conocimiento actual del compuesto de Sanofi

? Embarazo o lactancia;
? Mujeres en edad fértil que no usan un método anticonceptivo eficaz.

E.5 End points

E.5.1

Primary end point(s)

Percent change in HbA1c

Cambio en la HbA1c (%)

E.5.1.1

Timepoint(s) of evaluation of this end point

From baseline to 6 months

entre el momento basal y el Mes 6.

E.5.2

Secondary end point(s)

1- Proportion of patients who remain on assigned basal insulin therapy before intensification (persistent with assigned therapy)
2- Proportion of patients who remain on assigned basal insulin therapy whether intensification occurred or not
3- Proportion of patients who achieve target HbA1c (<6.5%, <7%, <7.5%,<8.0%)
4- Proportion of patients with HbA1c target (thresholds listed above) (attainment of metabolic benefit) without documented (blood glucose [BG] ? 70 mg/dl, [3.9 mmol/L]) symptomatic or severe
5- Proportion of patients with HbA1c target (thresholds listed above) (attainment of metabolic benefit) without documented (BG <54 mg/dl, [3.0 mmol/L]) symptomatic or severe hypoglycemia
6- Percent change in HbA1c
7- Percentage of patients whose HbA1c decreased at least 0.5%
8- Percentage of patients whose HbA1c decreased at least 0.5%
9- Percentage of patients requiring intensification and time to intensification,
10- Change in fasting plasma glucose

1- Proporción de pacientes que continúan con el tratamiento asignado de insulina basal antes de la intensificación (persistentes con el tratamiento asignado)
2- Proporción de pacientes que continúan con el tratamiento asignado de insulina basal en el Mes 6 y en el Mes 12, tanto si se produce intensificación como si no;
3- Proporción de pacientes que logran el objetivo de HbA1c de < 6,5 %, < 7 %, < 7,5 %, < 8,0 %) en el Mes 6 y en el Mes 12;
4- Proporción de pacientes que alcanzan el objetivo de HbA1c (umbrales antes mencionados) (consecución de beneficio metabólico) en el Mes 6 y en el Mes 12 sin hipoglucemia sintomática o severa documentada (glucemia ? 70 mg/dl [3,9 mmol/l]) (según la definición del Grupo de trabajo de la ADA sobre la Hipoglucemia) (1) en cualquier momento del día y de la noche (0:00-5:59);
5- Proporción de pacientes que alcanzan el objetivo de HbA1c (umbrales antes mencionados) (consecución de beneficio metabólico) en el Mes 6 y en el Mes 12 sin hipoglucemia sintomática o severa documentada (glucemia < 54 mg/dl [3,0 mmol/l]) (según la definición del Grupo de Trabajo de la ADA sobre la Hipoglucemia) (1) en cualquier momento del día y de la noche (0:00-5:59);
6- Cambio en la HbA1c (%)
7- Porcentaje de pacientes cuya HbA1c ha descendido al menos un 0,5 %
8- Porcentaje de pacientes cuya HbA1c ha descendido al menos un 0,5 %
9- Porcentaje de pacientes que requieren intensificación
10- Cambio en la glucosa plasmática en ayunas

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 2, 3, 4, 5 : at Month 6 and Month 12
6 : From baseline to Month 12
7 : at Month 6 and Month 12
8 : at Month 6 and maintained at Month 12
9 : at Month 6 and Month 12
10 : From baseline to Month 6 and Month 12

1-5: en el Mes 6 y en el Mes 12;
6: entre el momento basal y el Mes 12;
7: en el Mes 6 y en el Mes 12;
8: al Mes 6 y se ha mantenido al Mes 12;
9: en el Mes 6 y en el Mes 12, y tiempo transcurrido hasta la intensificación.
10- entre el momento basal y el Mes 6 y el Mes 12.

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

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)

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

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

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

122

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

Última visita del último paciente

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 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:

400

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

180

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

Yes

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

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

580

F.4.2.2

In the whole clinical trial

580

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

Ninguno

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

2015-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-10-20

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