Clinical Trials Register

Summary
EudraCT Number:	2015-005357-12
Sponsor's Protocol Code Number:	I8B-MC-ITRN
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:	2017-04-04
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

2015-005357-12

A.3

Full title of the trial

Protocol I8B-MC-ITRN
A Prospective, Randomized, Double-Blind Comparison of LY900014 to Insulin Lispro, Both in Combination with Insulin Glargine or Insulin Degludec in Adults with Type 2 Diabetes

Protocolo I8B-MC-ITRN
Estudio prospectivo, aleatorizado y doble ciego en el que se compara LY900014 con insulina lispro, ambos en combinación con insulina glargina o insulina degludec, en adultos con diabetes de tipo 2 PRONTO-T2D

A.3.1

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

A study in people with type 2 diabetes to determine how well a meal-time
insulin, LY900014, controls diabetes compared to Humalog (insulin lispro)
when both are used along with a long-acting insulin

Estudio en personascon diabetes tipo 2 para determinar cómo de bien controla la diabetes la insulina prandial LY900014 en comparación con Humalog (insulina lispro) cuando ambas son usadas junto con una insulina de acción prolongada

A.3.2

Name or abbreviated title of the trial where available

PRONTO-T2D

A.4.1

Sponsor's protocol code number

I8B-MC-ITRN

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	Lilly S.A.
B.1.3.4	Country	Spain
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	Eli Lilly and Company
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	Lilly S.A.
B.5.2	Functional name of contact point	Gracia Montes
B.5.3	Address:
B.5.3.1	Street Address	Avenida de la Industria 30
B.5.3.2	Town/ city	Alcobendas (Madrid)
B.5.3.3	Post code	28108
B.5.3.4	Country	Spain
B.5.4	Telephone number	003491623 12 18
B.5.5	Fax number	003491623 12 18
B.5.6	E-mail	ensayosclinicos@lilly.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	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	insulin lispro (ultra rapid formulation)
D.3.2	Product code	LY900014
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULIN LISPRO
D.3.9.1	CAS number	133107-64-9
D.3.9.4	EV Substance Code	SUB08198MIG
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	100
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.2.1.1.1	Trade name	Humalog
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland B.V.
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	INSULIN LISPRO
D.3.9.1	CAS number	133107-64-9
D.3.9.4	EV Substance Code	SUB08198MIG
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	100
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.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 II Diabetes Mellitus

Diabetes Mellitus tipo II

E.1.1.1

Medical condition in easily understood language

Type 2 Diabetes

Diabetes Tipo II

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	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10020639
E.1.2	Term	Hyperglycemia
E.1.2	System Organ Class	100000004861

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 test the hypothesis that LY900014 is noninferior to insulin lispro on glycemic control (NIM = 0.4% for HbA1c) in patients with T2D, when administered as prandial insulin (0 to 2 minutes prior to the meal), in combination with basal insulin glargine or insulin degludec for 26 weeks.

Contrastar la hipótesis según la cual LY900014 no es inferior a la insulina lispro desde el punto de vista del control glucémico (margen de no inferioridad [MNI] = 0,4 % para la HbA1c) en pacientes con DT2, cuando se administra como insulina prandial (en los 2 minutos anteriores a la comida), en combinación con una insulina basal (insulina glargina o insulina degludec), durante 26 semanas.

E.2.2

Secondary objectives of the trial

Secondary objectives include testing the hypothesis that LY is superior to insulin lispro in controlling 1 and 2 hour postprandial glucose (PPG) excursions, when administered as prandial insulin. To test the hypothesis that LY is superior to insulin lispro on improving glycemic control (HbA1c) when administered as prandial insulin.

Los objetivos secundarios incluyen la evaluación de la hipótesis según la cual LY es superior a la insulina lispro desde el punto de vista del control de las fluctuaciones de la glucosa posprandial (GPP) al cabo de 1 y 2 horas, cuando se administra como insulina prandial. Contrastar la hipótesis de que LY es superior a la insulina lispro desde el punto de vista de la mejoría del control glucémico (HbA1c), cuando se administra como insulina prandial.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

You can take part in this study if:
· You were diagnosed with type 2 diabetes at least one year ago.
· You are 18 years old or older.
· You are already being treated with insulin allowed for study participation.
· Your blood glucose levels are within allowed limits for study participation.

Puede participar en este estudio si:
· Le han diagnosticado diabetes de tipo 2 hace al menos un año.
· Tiene 18 años como mínimo.
· Ya recibe una insulina de las permitidas para participar en el estudio.
· Sus valores de glucemia se encuentran dentro de los límites aceptables para participar en el estudio.

E.4

Principal exclusion criteria

You cannot take part in this study if:
· You have had emergency treatment for very low blood glucose or poor blood glucose control in the last 6 months.
· You are taking certain diabetes medications that are not allowed for study participation.
· You have major problems with your heart, kidneys, liver, or you have a blood disorder.
You have had or are now being treated for certain types of cancer.

No puede participar en este estudio si:
· Ha recibido tratamiento de urgencia por presentar valores de glucemia muy bajos o mal control glucémico en los últimos 6 meses.
· Toma medicamentos para la diabetes que no están permitidos para participar en el estudio.
· Tiene algún trastorno cardiaco, renal o hepático importante o padece algún trastorno hematológico.

E.5 End points

E.5.1

Primary end point(s)

Difference between LY900014 and insulin lispro in change from baseline to Week 26 in HbA1c

Diferencia entre LY900014 y la insulina lispro en la variación de la concentración de HbA1c desde el período basal hasta la semana 26.

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks

26 semanas

E.5.2

Secondary end point(s)

1. Difference between LY900014 and insulin lispro in the 1-hour or 2-hour PPG excursion (serum glucose measured 1 hour or 2 hours after the start of the meal minus fasting serum glucose) from an MMTT at Week 26
2. Difference between LY900014 and insulin lispro in change from baseline to Week 26 in HbA1c
3. Rate (events/patient/100 years) of severe hypoglycemic events from baseline through Week 26
4. Rate (events/patient/year and/or events/patient/30 days) and incidence (percent of patients with at least 1 event) of documented symptomatic postmeal hypoglycemia within 1 and 2 hours after start of a meal from baseline through Week 26
5. Rate (events/patient/year and/or events/patient/30 days) and incidence (percent of patients with at least 1 event) of documented symptomatic hypoglycemic events from baseline through Week 26
6. Change from baseline 1,5-AG values at Week 26
7. Change from baseline 10-point SMBG values at Week 26
8. Change from baseline in total, basal and prandial insulin dose at Week 26
9. Change from baseline ITSQ regimen inconvenience and lifestyle flexibility domain scores at Week 26
10. The proportion of patients with HbA1c <7% and ≤6.5% at Week 26

1. Diferencia entre LY900014 y la insulina lispro en las fluctuaciones de la GPP al cabo de 1 y 2 horas (concentración sérica de glucosa determinada 1 o 2 horas después del inicio de la comida menos la concentración sérica de glucosa en ayunas), de acuerdo con una PTCM en la semana 26.
2. Diferencia entre LY900014 y la insulina lispro en la variación de la concentración de HbA1c desde el período basal hasta la semana 26.
3. Tasa (episodios/paciente/100 años) de episodios hipoglucémicos graves desde el período basal hasta la semana 26.
4. Tasa (episodios/paciente/año, episodios/paciente/30 días o ambos) e incidencia (porcentaje de pacientes con al menos 1 episodio) de hipoglucemia posprandial sintomática documentada en el transcurso de la primera y las dos primeras horas posteriores al inicio de una comida, desde el período basal hasta la semana 26.
5. Tasa (episodios/paciente/año, episodios/paciente/30 días o ambos) e incidencia (porcentaje de pacientes con al menos 1 episodio) de hipoglucemia sintomática documentada, desde el período basal hasta la semana 26.6. Variación de los valores de 1,5-AG en la semana 26 respecto al período basal.
7. Variación entre el período basal y la semana 26 en los perfiles de 10 puntos de GCP.
8. Variación entre el período basal y la semana 26 en la dosis de insulina prandial, basal y total.
9. Variación en la semana 26 respecto al periodo basal de las puntuaciones de los dominios del cuestionario ITSQ relativos a la flexibilidad del estilo de vida y las interferencias que ocasiona el tratamiento.
10. Porcentaje de pacientes que presentan una concentración de HbA1c < 7 % y ≤ 6,5 % en la semana 26.

E.5.2.1

Timepoint(s) of evaluation of this end point

26 weeks

26 semanas

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Czech Republic

Germany

Hungary

India

Italy

Japan

Korea, Republic of

Mexico

Puerto Rico

Russian Federation

Slovakia

Spain

Taiwan

United States

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

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:

536

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

134

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

245

F.4.2.2

In the whole clinical trial

1050

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)

Patients will resume their previous diabetes therapy after completing the trial

Tras completar el ensayo, los pacientes reanudarán el tratamiento contra la diabetes que recibieran antes de este.

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

2017-06-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-03-13

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