Clinical Trials Register

Summary
EudraCT Number:	2014-002263-15
Sponsor's Protocol Code Number:	LIXISL07016
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2014-06-24
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

2014-002263-15

A.3

Full title of the trial

Effects of GLP-1 Receptor Agonist Lixisenatide on Post-prandial Lipid Profile in Obese Type 2 Diabetic Patients

Effetti della Lixisenatide, agonista del recettore GLP-1, sul profilo lipidico post-prandiale in pazienti obesi con diabete di tipo 2

A.3.1

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

Effects of GLP-1 Receptor Agonist Lixisenatide on Post-prandial Lipid Profile in Obese Type 2 Diabetic Patients

Effetti della Lixisenatide sul profilo lipidico post-prandiale in pazienti obesi con diabete di tipo 2

A.4.1

Sponsor's protocol code number

LIXISL07016

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 S.p.A
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	sanofi aventis
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	quintiles spa
B.5.2	Functional name of contact point	gianfrancesco sartini
B.5.3	Address:
B.5.3.1	Street Address	Via Roma 108
B.5.3.2	Town/ city	Cassina De’ Pecchi (MI)
B.5.3.3	Post code	20060
B.5.3.4	Country	Italy
B.5.4	Telephone number	003902957941
B.5.6	E-mail	gianfrancesco.sartini@quintiles.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	Lyxumia
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis recherche & developpment
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.3.1	Product name	Lyxumia
D.3.2	Product code	AVE0010
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	LIXISENATIDE
D.3.9.1	CAS number	320367-13-3
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	LIXISENATIDE
D.3.9.4	EV Substance Code	SUB32251
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LIXISENATIDE
D.3.9.1	CAS number	320367-13-3
D.3.9.2	Current sponsor code	na
D.3.9.3	Other descriptive name	LIXISENATIDE
D.3.9.4	EV Substance Code	SUB32251
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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

Effect of GLP-1 receptor agonist lixisenatide on post-prandial lipid profile in obese patients

Effetti della Lixisenatide, agonista del recettore GLP-1, sul profilo lipidico post-prandiale in pazienti obesi con diabete di tipo 2

E.1.1.1

Medical condition in easily understood language

diabets

diabete

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

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 evaluate the ability of lixisenatide to modulate post-prandial hyperlipidemia: in particular the effects on plasma changes in triglycerides in obese Type II diabetes patients.

E.2.2

Secondary objectives of the trial

to evaluate:
The effect of lixisenatide on the following post prandial lipids: plasma cholesterol, APO B48; free fatty acid, lipoprotein distribution and LDL oxidation.
The effect of lixisenatide on post-prandial plasma glucose, insulin and C-peptide and glucagon
The effect of lixisenatide on low-grade inflammation (cytokines and stress oxidative markers), present in NIDDM and obesity.
The effect of lixisenatide on microvascular dysfunction.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients, 18-70 years of age
2. Diagnosis of Type 2 diabetes mellitus (T2DM) treated with Metformin (≥ 1.5 g/day) and Obesity (BMI > 30 kg/m2) and the following other abnormalities:
• Abdominal obesity (waist circumference > 102 cm in men and > 88 cm in women), according to NCEP-ATP III (2001)
• HbA1c ≥ 7 and ≤ 8.5 %. After Sponsor approval, providers might reasonably suggest more stringent HbA1c values (such as 6.5%) for selected individual patients, if this can be managed without significant hypoglycemia or other treatment adverse effects.. Appropriate patients might include those with short duration of diabetes, long life expectancy, and no significant CVD
• Hypertriglyceridemia (fasting triglyceride levels between 150 mg/dl and 600 mg/dl), cholesterol <300 mg/dl, and/or low high-density lipoprotein (HDL) cholesterol (i.e. serum HDL-cholesterol <40 mg/dl in men and < 50 mg/dl in women)
3. Signed written informed consent

E.4

Principal exclusion criteria

1. At screening: age < legal age of majority
2. Type 1 diabetes mellitus
3. Smoking
4. History of hypoglycaemia unawareness
5. Thyroid disease even if under appropriate hormonal replacement therapy or thyroid suppressant (TSH > 5 mU/l with clinical symptoms of hypothyroidism)
6. Hepatic disease (AST or ALT > 2 times the upper limit of normal)
7. Renal disease (serum creatinine > 1.7 times the upper limit of normal).
8. A history of coronary heart disease, cerebrovascular disease or peripheral arterial disease in the 6 months before enrolment and/or concomitant treatment with calcium antagonists, Beta blockers and/or nitrates.
9. Women of childbearing potential with no effective contraceptive method, pregnancy or lactation. Women of childbearing potential (pre-menopausal, or women not surgically sterile for at least 3 months prior to the time of screening) must have a confirmed negative pregnancy test at screening visit. They must use an effective contraceptive method throughout the study.
10. History of malignancies
11. Known history of drug or alcohol abuse within 6 months prior to the time of screening
12. Uncontrolled or inadequately controlled hypertension at the time of screening with a resting systolic or diastolic blood pressure >180 mmHg or >95 mmHg, respectively
13. Triglycerides > 600 mg/dl
14. History of chronic pancreatitis or of idiopathic acute pancreatitis
15. History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
16. Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within 3 months prior to the time of screening
17. Any other clinically significant abnormality identified on physical examination, laboratory tests, ECG or vital signs at the time of screening that in the judgment of the investigator or any sub- investigator would make implementation of the protocol or interpretation of the study results difficult or would preclude the safe participation of the subject in this protocol.
18. Use of any glucose-lowering agent(s) other than metformin in the 3 months prior to screening
19. Treatment with metformin at a daily dose < 1.5 g/day
20. Use of lipid lowering therapy and/or weight lowering drugs within 3 months prior to screening
21. Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one consecutive week or more within 3 months prior to the time of screening
22. Use of any investigational drug within 3 months prior to screening
23. Patients considered by the investigator or any sub investigator as inappropriate for this study for any medical, psychological, social, or geographical reason (e.g. patients that do not take their breakfast in the morning, patients unable to fully understand the nature, scope, and possible consequences of the study; patients unable to fully understand patient’s study documents; impossibility to meet specific protocol requirements, such as scheduled visits; being unable or unwilling to do blood glucose monitoring using the sponsor-provided blood glucose meter at home; likelihood of requiring treatment with drugs not permitted by the clinical study protocol, night shift workers, etc)
24. Patient is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
25. Patient who withdraws consent during the screening.
26. Any contra-indication to metformin according to local labelling
27. Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (i.e. worsening) and not controlled (i.e. prolonged nausea and vomiting) gastroesophageal reflux disease within 6 months prior to the time of screening
28. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease
29. Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g. multiple endocrine neoplasia syndromes)
30. Any previous treatment with lixisenatide (e.g. participation in a previous study with lixisenatide)
31. Allergic reaction to any GLP-1 receptor agonist in the past (e.g. exenatide, liraglutide) or to metacresol.

E.5 End points

E.5.1

Primary end point(s)

• Effect of lixisenatide on plasma changes on tryglycerides after 10 weeks of treatment (AUC0-480 min)

E.5.1.1

Timepoint(s) of evaluation of this end point

10 weeks

E.5.2

Secondary end point(s)

• Effect of lixisenatide on plasma changes of:
- triglycerides, on the 2nd day of treatment (AUC0-480 min)
- plasma cholesterol, APO B48 on the 2nd day and after 10 weeks of treatment
- free fatty acid on the 2nd day and after 10 weeks of treatment
- lipoprotein distribution on the 2nd day and after 10 weeks of treatment
- LDL oxidation on the 2nd day and after 10 weeks of treatment
- post-prandial plasma glucose, insulin and C-peptide, glucagon (AUC0-480 min)
• Effect of lixisenatide on low grade inflammation (cytokines and stress oxidative markers) on the 2nd day and after 10 weeks of treatment
• Effect of lixisenatide on microvascular dysfunction on the 2nd day and after 10 weeks of treatment.

E.5.2.1

Timepoint(s) of evaluation of this end point

10 weeks

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

Yes

E.8.4

The trial involves multiple sites in the 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

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

12 months

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

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.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)

standard terapy

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

2014-10-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-10-09

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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