Clinical Trials Register

Summary
EudraCT Number:	2011-001254-29
Sponsor's Protocol Code Number:	I2R-MC-BIAM
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-28
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-001254-29

A.3

Full title of the trial

The Impact of LY2605541 versus Insulin Glargine for
Patients with Type 2 Diabetes Mellitus Advanced to
Multiple Injection Bolus Insulin with Insulin Lispro: a
Double-Blind, Randomized, 26-Week Study
The IMAGINE 4 Study

Effetti di LY2605541 e insulina Lispro rispetto a insulina glargine e insulina Lispro in pazienti con diabete mellito di tipo 2 in terapia insulinica multi-iniettiva: Studio in doppio cieco, randomizzato, di 26 settimane

A.3.1

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

A Study in Type 2 Diabetes

Studio su pazienti diabetici di tipo 2

A.3.2

Name or abbreviated title of the trial where available

IMAGINE 4

A.4.1

Sponsor's protocol code number

I2R-MC-BIAM

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	ELI LILLY
B.1.3.4	Country	Italy
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	Boehringer Ingelheim International GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Eli Lilly
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Erl Wood Manor, Sunninghill Road
B.5.3.2	Town/ city	Windlesham
B.5.3.3	Post code	GU20 6PH
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+441276483369
B.5.5	Fax number	+441276483378
B.5.6	E-mail	EU_Lilly_Clinical_Trials@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	LY2605541
D.3.2	Product code	LY2605541
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.3.9.2	Current sponsor code	LY2605541
D.3.9.3	Other descriptive name	Basal Insulin Lispro
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	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 Glargin
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 GLARGINE
D.3.9.1	CAS number	160337-95-1
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	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: 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	HUMALOG PEN*5PENNE 100U/ML 3ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ELI LILLY ITALIA SpA
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.3.4	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	Yes
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 2 Diabetes Mellitus

Pazienti diabetici di Tipo 2

E.1.1.1

Medical condition in easily understood language

Diabetes

Diabete

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10012613
E.1.2	Term	Diabetes mellitus non-insulin-dependent
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

The primary objective is to demonstrate that glycemic control, as measured by change in hemoglobin A1c (HbA1c) from baseline to 26 weeks, for LY2605541 is non-inferior compared with insulin glargine when each is combined with preprandial insulin lispro with or without metformin in patients with T2DM who have not achieved adequate glycemic control with at least 1 injection of insulin daily with or without OAMs. The non-inferiority margin is 0.4%.

L'obiettivo primario è quello di dimostrare che il controllo glicemico, come misurato dal cambiamento dell'emoglobina A1c (HbA1c) dal basale a 26 settimane, per LY2605541 non è inferiore rispetto all'insulina glargine, quando combinate con insulina lispro preprandiale con o senza metformina in pazienti con diabete mellito di tipo 2 che non hanno raggiunto un adeguato controllo glicemico con almeno 1 iniezione di insulina al giorno, con o senza OAM. Il margine di non inferiorità è di 0,4%.

E.2.2

Secondary objectives of the trial

The gated secondary objectives are to demonstrate that LY2605541 is superior to insulin glargine (each in combination with preprandial insulin lispro) for: 1. Nocturnal hypoglycemia rate during 26 weeks of treatment 2. Proportion of patients with HbA1c <7.0% at 26 weeks using last observation carried forward (LOCF) and no nocturnal hypoglycemia during the 26 weeks 3. HbA1c change from baseline after 26 weeks of treatment 4. Proportion of patients with HbA1c <7.0% after 26 weeks of treatment (LOCF) 5. Fasting serum glucose (FSG) by laboratory measurement after 26 weeks of treatment 6. Total hypoglycemia rate during the 26 weeks of treatment.

Gli obiettivi secondari gated servono a dimostrare che LY2605541 è superiore all’insulina glargine (entrambe in combinazione con insulina lispro preprandiale) per: 1. Percentuale di ipoglicemia notturna durante le 26 settimane di trattamento 2. Proporzione di pazienti con HbA1c <7,0% a 26 settimane con ultima osservazione portata a termine (LOCF) e nessuna ipoglicemia notturna durante le 26 settimane 3. Variazione HbA1c dal basale dopo 26 settimane di trattamento 4. Proporzione di pazienti con HbA1c <7,0% dopo 26 settimane di trattamento (LOCF) 5. Glicemia a digiuno (FSG) mediante misurazione di laboratorio dopo 26 settimane di trattamento 6. Percentuale totale di ipoglicemia durante le 26 settimane di trattamento.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male or female patients diagnosed with T2DM (for at least 1 year), aged ≥18 years, with a body mass index ≤45.0 kg/m2. Patients should have HbA1c value ≥7.0% to <12.0% at screening; and be taking at least 1 injection of insulin per day with or without OAMs

Pazienti di sesso maschile o femminile con diagnosi di diabete mellito di tipo 2 (per almeno 1 anno), di età ≥ 18 anni, con un indice di massa corporea ≤ 45,0 kg / m 2. I pazienti devono avere un valore di HbA1c compreso tra ≥ 7,0% e < 12,0% allo screening e ricevere almeno 1 iniezione di insulina al giorno, con o senza OAM.

E.4

Principal exclusion criteria

. Patients should not have had any episode of severe hypoglycemia or have had 2 or more emergency room visits/ hospitalizations due to poor glucose control or 1 or more hospitalizations for episodes of ketoacidosis or hyperosmolar state/coma within 6 months prior to Visit 1.

. I pazienti non devono aver avuto alcun episodio di ipoglicemia grave o non essersi sottoposti a 2 o più visite al pronto soccorso/ricoveri a causa di scarso controllo glicemico o 1 o più ricoveri per episodi di chetoacidosi o stato iperosmolare/coma entro 6 mesi prima della Visita 1.

E.5 End points

E.5.1

Primary end point(s)

HbA1c change from baseline, HbA1c, nocturnal and overall hypoglycemia, FSG from central laboratory, FBG from SMBG, FBG intra-patient variability (SMBG) as measured by standard deviation, proportion of patients with HbA1c < 7.0% without nocturnal hypoglycemia, proportion of patients with HbA1c <7.0% and ≤6.5%, SMBG 9-point profiles, body weight change, and basal and bolus insulin dose.

Modifica dell'HbA1c rispetto al basale, ipoglicemia HbA1c notturna e generale, FSG dal laboratorio centrale, FBG da SMBG, variabilità intra-paziente FBG (SMBG) come misurato dalla deviazione standard, proporzione di pazienti con HbA1c < 7,0% senza ipoglicemia notturna, proporzione di pazienti con HbA1c < 7,0% e profili a 9 punti SMBG ≤ 6,5%, variazione del peso corporeo e dose di insulina al basale e bolo.

E.5.1.1

Timepoint(s) of evaluation of this end point

26 weeks

26 settimane

E.5.2

Secondary end point(s)

TEAEs, SAEs, selected adjudicated cardiovascular events, AEs of special interest, antibodies to LY2605541, treatment exposure, chemistry panel measures, lipid panel measures, hematology panel measures, urinalysis measures, and vital signs.

TEAE, eventi avversi gravi, eventi cardiovascolari aggiudicati selezionati, eventi avversi di particolare interesse, anticorpi anti LY2605541, esposizione al trattamento, misure del pannello chimico, misure del pannello lipidico, misure del pannello ematologico, valori delle analisi delle urine e segni vitali.

E.5.2.1

Timepoint(s) of evaluation of this end point

26 weeks

26 settimane

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

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

Australia

Brazil

Croatia

Israel

Japan

Mexico

Russian Federation

Taiwan

Turkey

United States

E.8.7

Trial has a data monitoring committee

Yes

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

Number of subjects for this age range:

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:

994

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

331

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

575

F.4.2.2

In the whole clinical trial

1325

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)

The Sponsor will not provide patients with ongoing supplies of study
medication after they have completed the study treatment period
because LY2605541 is experimental, while insulin glargine is readily
available.

Lo Sponsor non fornisce il farmaco alla fine dello studio in quanto Glargine è già sul mercato e LY non lo sarà alla fine dello studio.

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

2012-01-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-13

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

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