Clinical Trials Register

Summary
EudraCT Number:	2017-002374-39
Sponsor's Protocol Code Number:	I8B-MC-ITSI
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:	2017-11-15
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

2017-002374-39

A.3

Full title of the trial

Protocol I8B-MC-ITSI
A Prospective, Randomized, Double-Blind, Crossover Comparison Evaluating Compatibility and Safety of LY900014 and Insulin Lispro with an External Continuous Subcutaneous Insulin Infusion System in Adult Patients with Type 1 Diabetes (PRONTO-Pump)

Protocolo I8B-MC-ITSI
Estudio prospectivo, aleatorizado, doble ciego y comparación cruzada, en el que se evalúan la compatibilidad y la seguridad de LY900014 y la insulina lispro con un sistema externo de infusión continua de insulina subcutánea en pacientes adultos con diabetes de tipo 1 (PRONTO-Pump)

A.3.1

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

A study to compare the compatibility and safety of LY900014 with insulin lispro given by insulin pump in patients with type 1 diabetes

Un estudio en personas con diabetes tipo 1 para determinar la compatibilidad y la seguridad de LY900014 y la insulina lispro con un sistema externo de infusión continua de insulina subcutánea

A.3.2

Name or abbreviated title of the trial where available

PRONTO-Pump

A.4.1

Sponsor's protocol code number

I8B-MC-ITSI

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 17 52
B.5.5	Fax number	003491663 34 81
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

Diabetes Mellitus, Type 1

Diabetes mellitus de tipo 1

E.1.1.1

Medical condition in easily understood language

Type 1 Diabetes

Diabetes de tipo 1

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	PT
E.1.2	Classification code	10012601
E.1.2	Term	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

1-To compare LY900014 and insulin lispro with respect to the rate of suspected infusion set occlusions defined as unexplained hyperglycemia with blood glucose > 300 mg/dL (16.7 mmol/L) that does not decrease by >50 mg/dL (2.8 mmol/L) following a correction insulin bolus delivered via the pump and that leads to an infusion set change

Comparar LY900014 y la insulina lispro respecto a la tasa de presuntas oclusiones del equipo de infusión, definidas como episodios de hiperglucemia idiopática con un valor de glucemia > 300 mg/dl (16,7 mmol/l) que no disminuya > 50 mg/dl (2,8 mmol/l) tras la administración de una dosis correctiva de insulina en bolo mediante la bomba y que motive el cambio del equipo de infusión.

E.2.2

Secondary objectives of the trial

To compare LY900014 and insulin lispro with respect to:
2.Incidence of suspected infusion set occlusions defined as unexplained hyperglycemia with blood glucose >300 mg/dL (16.7 mmol/L) that does not decrease by >50 mg/dL (2.8 mmol/L) following a correction insulin bolus delivered via the pump and that leads to an infusion set change
3.Rate and incidence of any suspected infusion set occlusions defined as unexplained hyperglycemia that leads to an infusion set change
4.Rate and incidence of premature infusion set changes by reason
5.Days until infusion set change
6.Total, basal, and bolus insulin dose
7.Interstitial glucose reduction rate from hyperglycemia following a non-meal-related correction insulin bolus delivered via the pump
8.Rate of severe hypoglycemic events

Comparar LY900014 y la insulina lispro respecto a:
2. Incidencia de las presuntas oclusiones del equipo de infusión, definidas como episodios de hiperglucemia idiopática con un valor de glucemia > 300 mg/dl (16,7 mmol/l) que no disminuya > 50 mg/dl (2,8 mmol/l) tras la administración de una dosis correctiva de insulina en bolo mediante la bomba y que motive el cambio del equipo de infusión.
3. Tasa e incidencia de cualquier presunta oclusión del equipo de infusión, definida como un episodio de hiperglucemia idiopática que motive el cambio del equipo de infusión.
4. Tasa e incidencia de los cambios precoces del equipo de infusión.
5. Días transcurridos hasta el cambio del equipo de infusión.
6. Dosis de insulina total, basal y en bolo.
7. Velocidad de disminución de la glucosa intersticial tras la administración de una dosis correctiva de insulina en bolo mediante la bomba que no guarde relación con las comidas.
8. Tasa de episodios hipoglucémicos graves.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-You are diagnosed with type 1 diabetes and have been using insulin continuously for at least 12 months
-You are 18 years of age or older
-You have been using an insulin pump with ‘rapid-acting insulin’ for at least 6 months and using the same rapid-acting insulin for at least the past 30 days
-You have experience using Continuous Glucose Monitoring (CGM) or Flash Glucose Monitoring (FGM) for at least 60 days during the past 12 months
-You have been using the MiniMed 530G or 630G (US) or the MiniMed 640G (EU) insulin pump for at least the past 30 days

-Le han diagnosticado diabetes de tipo 1 y ha tomado insulina de forma continua durante al menos 12 meses.
-Tiene al menos 18 años de edad.
-Ha utilizado una bomba de insulina con una "insulina de acción rápida" al menos durante 6 meses y la misma insulina de acción rápida, al menos durante los 30 últimos días.
-Tiene experiencia con los equipos de monitorización continua de la glucosa (MCG) o de monitorización instantánea de la glucosa (MIG) (los ha utilizado al menos durante 60 días en los 12 últimos meses).
-Ha utilizado una bomba de insulina MiniMed 530G o 630G (EE. UU.) o MiniMed 640G (UE) durante al menos los 30 últimos días.

E.4

Principal exclusion criteria

You have had more than 1 emergency treatment for very low blood glucose in the last 6 months.
You have had more than 1 emergency treatment for poor 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 that prevents you from study participation.

Ha recibido tratamiento de urgencia en más de 1 ocasión para tratar valores muy bajos de glucemia en los últimos 6 meses.
Ha recibido tratamiento de urgencia en más de 1 ocasión por presentar 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.
Ha recibido o recibe tratamiento para determinados tipos de cáncer, lo que impediría su participación en el estudio.

E.5 End points

E.5.1

Primary end point(s)

1-Rate (events/patient/30 days) of suspected infusion set occlusions defined as unexplained hyperglycemia with blood glucose (SMBG) >300 mg/dL (16.7 mmol/L) that does not decrease by >50 mg/dL (2.8 mmol/L) following a correction bolus delivered via the pump and that leads to an infusion set change during the 6-week treatment period

1. Tasa (episodios/paciente/30 días) de presuntas oclusiones del equipo de infusión, definidas como episodios de hiperglucemia idiopática con un valor de glucemia (GDP) > 300 mg/dl (16,7 mmol/l) que no disminuya > 50 mg/dl (2,8 mmol/l) tras la administración de una dosis correctiva en bolo mediante la bomba y que motive el cambio del equipo de infusión durante el período de tratamiento de 6 semanas.

E.5.1.1

Timepoint(s) of evaluation of this end point

during the 6-week treatment period

Durante el período de tratamiento de 6 semanas.

E.5.2

Secondary end point(s)

2-Incidence (percent of patients with at least 1 event) of suspected infusion set occlusions defined as unexplained hyperglycemia with blood glucose (SMBG) >300 mg/dL (16.7 mmol/L) that does not decrease by >50 mg/dL (2.8 mmol/L) following a correction bolus delivered via the pump and that leads to an infusion set change during the 6-week treatment period
3-Rate (events/patient/30 days) and incidence of any suspected infusion set occlusions defined as unexplained hyperglycemia that leads to an infusion set change during the 6-week treatment period
4-Rate (events/patient/30 days) and incidence of premature infusion set changes by reason during the 6-week treatment period
5-Days until infusion set change during the 6 week treatment period
6-Bolus/total insulin dose ratio at the end of the 6-week treatment period
7-Interstitial glucose reduction rate (glucose reduction [mg/dL and mmol/L] per minute) within 4 hours following a non-meal-related correction insulin bolus via the pump, from hyperglycemia (interstitial glucose >180 mg/dL (10.0 mmol/L) to recovery (interstitial glucose ≤180 mg/dL), from up to 6 weeks of CGM use
8-Rate (events/patient/100 years) of severe hypoglycemic events during the 6-week treatment period

2. Incidencia (porcentaje de pacientes que presenten al menos 1 episodio) de presuntas oclusiones del equipo de infusión, definidas como episodios de hiperglucemia idiopática con un valor de glucemia (GDP) > 300 mg/dl (16,7 mmol/l) que no disminuya > 50 mg/dl (2,8 mmol/l) tras la administración de una dosis correctiva en bolo mediante la bomba y que motive el cambio del equipo de infusión durante el período de tratamiento de 6 semanas.
3. Tasa (episodios/paciente/30 días) e incidencia de cualquier presunta oclusión del equipo de infusión, definida como un episodio de hiperglucemia idiopática que motive el cambio del equipo de infusión durante el período de tratamiento de 6 semanas.
4. Tasa (episodios/paciente/30 días) e incidencia de los cambios precoces del equipo de infusión durante el período de tratamiento de 6 semanas, clasificados según la razón.
5. Días transcurridos hasta el cambio del equipo de infusión durante el período de tratamiento de 6 semanas.
7. Velocidad de disminución de la glucosa intersticial (disminución de la glucosa [mg/dl y mmol/l] por minuto) en el transcurso de las 4 horas posteriores a la administración de una dosis correctiva de insulina en bolo mediante la bomba que no guarde relación con las comidas, desde un estado hiperglucémico (concentración de glucosa intersticial > 180 mg/dl [10 mmol/l]), hasta el restablecimiento de los valores (concentración de glucosa intersticial ≤ 180 mg/dl), a partir de los datos de MCG durante un período de hasta 6 semanas.
8. Tasa (episodios/paciente/100 años) de episodios hipoglucémicos graves durante el período de tratamiento de 6 semanas.

E.5.2.1

Timepoint(s) of evaluation of this end point

2_during the 6-week treatment period
3_during the 6-week treatment period
4_during the 6-week treatment period
5_during the 6-week treatment period
6_ at the end of the 6-week treatment period
7_from up to 6 weeks of CGM use
8_during the 6-week treatment period

2_Durante el período de tratamiento de 6 semanas.
3_Durante el período de tratamiento de 6 semanas.
4_Durante el período de tratamiento de 6 semanas.
5_Durante el período de tratamiento de 6 semanas.
6_al final del período de tratamiento de 6 semanas.
7_a partir de los datos de MCG durante un período de hasta 6 semanas.
8_Durante el período de tratamiento de 6 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

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

Compatibility

Compatibilidad

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

E.8.1.6

Cross over

Yes

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

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

Spain

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 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:

F.1.3

Elderly (>=65 years)

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

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

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients will resume their previous diabetes therapy after completing
the trial.

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

2017-12-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-12-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-09-04

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IMP with orphan designation in the indication
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