Clinical Trials Register

Summary
EudraCT Number:	2011-000828-15
Sponsor's Protocol Code Number:	I4L-MC-ABEC
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:	2012-01-24
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

2011-000828-15

A.3

Full title of the trial

Protocol I4L-MC-ABEC(a) A ProspEctive, Randomized, DoubLE-Blind CoMparison of a Long-Acting Basal Insulin Analog LY2963016 to Lantus in Adult PatiENTs with Type 2 Diabetes Mellitus: The ELEMENT 2 Study

Studio prospettico, randomizzato, in doppio cieco, di confronto di un analogo dell' insulina basale a lunga azione LY2963016 con Lantus in pazienti adulti con diabete mellito di tipo 2

A.3.1

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

Studio prospettico, randomizzato, in doppio cieco, di confronto di un analogo dell’insulina basale a lunga azione LY2963016 con Lantus in pazienti adulti con diabete mellito di tipo 2

A.3.2

Name or abbreviated title of the trial where available

The Element 2 study

Studio: Element 2

A.4.1

Sponsor's protocol code number

I4L-MC-ABEC

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	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	Eli Lilly
B.5.2	Functional name of contact point	Clinical Trial Information Desk
B.5.3	Address:
B.5.3.1	Street Address	via gramsci 731
B.5.3.2	Town/ city	sesto fiorentino
B.5.3.3	Post code	50019
B.5.3.4	Country	Italy
B.5.4	Telephone number	0554257050
B.5.5	Fax number	0554257348
B.5.6	E-mail	eu_lilly_clinical_trial@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	biosimilar insuline glargine
D.3.2	Product code	LY2963016
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	160337951
D.3.9.2	Current sponsor code	LY2963016
D.3.9.3	Other descriptive name	biosimilar insulin glargine
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international 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	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	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	LANTUS*SC 10FL 100UI/ML 5ML
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS 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 GLARGINE
D.3.9.1	CAS number	160337951
D.3.9.3	Other descriptive name	insulin glargine
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international 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	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

diabete mellito tipo 2

E.1.1.1

Medical condition in easily understood language

type 2 diabetes mellitus

diabete mellito 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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10049746
E.1.2	Term	Insulin-requiring type II 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

The primary objective of this study is to test the hypothesis that LY2963016 administered once daily (QD) is noninferior to Lantus administered QD, as measured by change in hemoglobin A1c (HbA1c) from baseline to 24 weeks, when used in combination with OAMs

l’obiettivo primario di questo studio è di testare l’ipotesi che LY2963016 somministrato una volta al dì (QD) sia non inferiore a Lantus (QD), in base alla misurazione della variazione nell’emoglobina A1c (HbA1c) dal basale a 24 settimane, quando usato in combinazione con farmaci antiperglicemici orali (oral antihyperglycemic medications, OAM).

E.2.2

Secondary objectives of the trial

compare safety of LY2963016 relative to Lantus (eg, incidence of anti-insulin antibodies, hypoglycemia, adverse events [AEs]) when used in combination with OAMs. compare LY2963016 relative to Lantus for other efficacy variables (eg, change in HbA1c at 4, 8, 12, 16, and 20 weeks, 7-point selfmonitored blood glucose profiles [as plasma equivalent values], percentage of patients with HbA1c <7%, percentage of patients with HbA1c ≤6.5%). compare LY2963016 relative to Lantus with regard to intrapatient blood glucose (BG) variability, basal insulin dose, and weight, when used in combination with OAMs. test the hypothesis that Lantus is noninferior to LY2963016 (QD), as measured by change in HbA1c from baseline to 24 weeks, when used in combination with OAMs. compare LY2963016 relative to Lantus for patient-reported outcomes as measured by responses to the ALBSS and the ITSQ

Confrontare sicurezza di LY2963016 relativa a Lantus quando usato in combinazione con gli OAM. Confrontare LY2963016 rispetto a Lantus per altre variabili di efficacia (ad es., variazione di HbA1c a 8, 12, 16, e 20 settimane, profili auto-monitorati della glicemia [SMBG] a 7 punti [come valori plasma equivalenti], percentuale di pazienti con HbA1c <7%, percentuale di pazienti con HbA1c ≤6,5%). Confrontare LY2963016 rispetto a Lantus riguardo alla variabilità della glicemia (BG) intrapaziente, la dose basale di insulina e il peso, quando usati in combinazione con gli OAM. Testare l’ipotesi che Lantus sia non inferiore a LY2963016 (QD), in base alla misurazione della variazione di HbA1c dal basale a 24 settimane, quando usato in combinazione con gli OAM. Confrontare LY2963016 rispetto a Lantus per gli outcome riportati dai pazienti misurati in base alle risposte Indagine ALBSS e al ITQS

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

[1] Have T2DM based on WHO classification. [2] Are ≥18 years of age. [3] Have been receiving 2 or more OAMs at stable doses for the 12 weeks prior to Visit 1, with or without Lantus. [4] Have an HbA1c ≥7.0% and ≤11.0% if insulin naïve; if previously on Lantus, then HbA1c ≤11.0%. [5] (BMI) ≤45 kg/m2. [6] As determined by the investigator, are capable and willing to do the following: • perform SMBG • complete patient diaries as required • use covered insulin vial and syringe according to study instructions • are receptive to diabetes education • comply with required study treatment and study visits. [7] Have given written informed consent to participate in this study in accordance with local regulations.

I pazienti con T2DM di età ≥18 con indice di massa corporea ≤45 e in terapia con 2 o più OAM (con o senza Lantus) da almeno 12 settimane prima della Visita 1 saranno inclusi nello studio. Pazienti con HbA1c ≥7,0 e ≤ 11,0 se naïve all’insulina; se nel pre-studio Lantus, HbA1c ≤11,0. Saranno esclusi i pazienti con malattia epatica, cardiaca o gastrointestinale significativa. Saranno esclusi i pazienti con cancro attivo o con tumore nei precedenti 5 anni (con eccezione del carcinoma a cellule basali o carcinoma in situ). Saranno anche esclusi i pazienti con resistenza eccessiva all’insulina (cioè, dose totale di insulina ≥1,5U/kg) o con ipersensibilità al Lantus o ai suoi eccipienti.

E.4

Principal exclusion criteria

[8] Have used any other insulin except Lantus, including commercial and investigational insulins within the previous 30 days. [9] Have been exposed to a biosimilar insulin glargine within the previous 90 days. [10] Have a history of taking basal bolus therapy or who, in the investigator's opinion, require mealtime insulin in order to achieve target control. [11] Have used short-acting glucagon like peptide (GLP-1) agonist (eg, exenatide) or long-acting GLP-1 agonist (eg, liraglutide) within the previous 90 days. [12] Have used pramlintide within the previous 30 days. [13] Have excessive insulin resistance at study entry (total insulin dose ≥1.5 U/kg). [14] Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study. [15] Have known hypersensitivity or allergy to Lantus or its excipients. [16] Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intra-articular, intraocular, and inhaled preparations) or have received such therapy within 4 weeks immediately preceding Visit 1. [17] Have obvious signs or symptoms, or laboratory evidence, of liver disease [ALT]; or [AST] greater than 2.5 times the upper limit of the reference range; or albumin value above or below the normal reference range [18] Have one of the following concomitant diseases: significant cardiac or gastrointestinal disease [19] Have a history of renal transplantation, are currently receiving renal dialysis or have a serum creatinine greater than 2.0 mg/dL [20] Have had a blood transfusion or severe blood loss within 3 months prior to Visit 1 or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia. [21] Patients with active cancer or personal history of cancer within the previous 5 years [27] Are pregnant or intend to become pregnant during the course of the study or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable. [28] Women who are breastfeeding.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

24-week treatment and 4- week post-treatment follow-up study in adult patients with type 2 diabetes mellitus (T2DM).

24 settimane di trattamento e 4 settimane di follow-up post- trattamento

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

24-week treatment and 4- week post-treatment follow-up study in adult patients with type 2 diabetes mellitus (T2DM).

24 settimane di trattamento e 4 settimane di follow-up post- trattamento

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

Yes

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

Korea, Republic of

Mexico

Russian Federation

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:

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

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

355

F.4.2.2

In the whole clinical trial

792

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 approximately 4-weeks poststudy endpoint, patients will have a final office visit (Visit 801), when end-of-study assessments will be performed.

A circa 4 settimane dopo l'endpoint di studio , i pazienti avranno una visita finale in ambulatorio (Visita 801), dove saranno eseguite le valutazioni di fine 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

2011-08-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-06-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-09-18

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