Clinical Trials Register

Summary
EudraCT Number:	2015-001850-13
Sponsor's Protocol Code Number:	GLP-1/MCI
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-12-18
Trial 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

2015-001850-13

A.3

Full title of the trial

Long-acting exenatide: a tool to stop cognitive decline in patients with mild cognitive impairment with or without dysglycemia?

Exenatide a lunga durata di azione: un possibile strumento nel rallentamento della progressione del declino cognitivo in pazienti con o senza disglicemia?

A.3.1

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

Study of the possible effects of an anti-diabetic drug (GLP-1 agonist) in slowing cognitive dysfunction in subjects with or without reduced glucose tolerance.

Studio dei possibili effetti di un farmaco anti-diabetico (GLP-1 agonista) nel rallentamento della disfunzione cognitiva in soggetti con o senza ridotta tolleranza agli zuccheri.

A.3.2

Name or abbreviated title of the trial where available

Effects of exenatide on subjects with moderate cognitive impairment

Effetti dell¿ exenatide su soggetti con disfunzione cognitiva moderata

A.4.1

Sponsor's protocol code number

GLP-1/MCI

A.5.4

Other Identifiers

Name:

GLP-1/MCI

Number:

GLP-1/MCI

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	AZIENDA OSPEDALIERO-UNIVERSITARIA DI PARMA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	DRINN Project
B.4.2	Country	Italy
B.4.1	Name of organisation providing support	FONDI DI DIPARTIMENTO
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	Azienda Ospedaliero-Universitaria di Parma
B.5.2	Functional name of contact point	Segreteria Scientifica del Comitato
B.5.3	Address:
B.5.3.1	Street Address	via Gramsci 14
B.5.3.2	Town/ city	Parma
B.5.3.3	Post code	43126
B.5.3.4	Country	Italy
B.5.4	Telephone number	0521703013
B.5.5	Fax number	0521704702
B.5.6	E-mail	gideluca@ao.pr.it

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	BYDUREON -SC 4 PEN 2 MG 0.65ML
D.2.1.1.2	Name of the Marketing Authorisation holder	Astrazeneca
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.3.1	Product name	EXENATIDE
D.3.4	Pharmaceutical form	Powder and solvent for suspension 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	EXENATIDE
D.3.9.1	CAS number	141758-74-9
D.3.9.2	Current sponsor code	NON APPLICABILE
D.3.9.3	Other descriptive name	NON APPLICABILE
D.3.9.4	EV Substance Code	SUB21818
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Moderate cognitive impairment

Ridotta funzionalit¿ cognitiva

E.1.1.1

Medical condition in easily understood language

Moderate cognitive impairment

Ridotta funzionalit¿ cognitiva

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10009846
E.1.2	Term	Cognitive impairment
E.1.2	System Organ Class	100000004852

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 target GLP1-receptor in MCI patients with or without dysglycemia with a convenient (once weekly administration) long acting GLP1-receptor agonist to assess the efficacy in preventing/slowing the progression of cognitive dysfunction in subjects

Attivare il recettore del GLP-1 in pazienti con o senza ridotta tolleranza glucidica e disfunzione cognitiva moderata mediante l¿utilizzo di un farmaco analogo GLP-1 a lunga durata di azione (1 somministrazione sottocutanea/settimana) in al fine di verificarne l¿efficacia nel prevenire/ritardare la progressione della disfunzione cognitiva.

E.2.2

Secondary objectives of the trial

NOT APPLICABLE

NON APPLICABILE

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-patients capable of giving informed consent; diagnosis of MCI according to the Petersen clinical criteria (Petersen criteria: presence of subjective memory loss, preferably corroborated by an informant; demonstration of a memory impairment by cognitive testing; preserved general intellectual functioning as estimated by performance on a vocabulary test; intact ability to perform activities of daily living and absence of dementia); the expected corrected scores at the MMSE are from 24 to 27. ( , ).; age >50<80 yrs; stable medication for the past 3 months; Caucasian ethnicity.

• Pazienti capaci di fornire il consenso informato
• Diagnosi di MCI secondo i criteri clinici di Petersen (presenza soggettiva di perdita della memoria preferibilmente confermata da un famigliare, dimostrazione di alterazione ad un test cognitivo, funzioni intellettive generali preservate stimate con la valutazione con un test di vocabolario, conservata abilità a svolgere attività relative alla vita di tutti i giorni ed assenza di demenza). Gli score attesi corretti con il MMSE sono dal 24 to 27.
• età >50<80 anni
• terapia farmacologica stabile negli ultimi 3 mesi
• etnia caucasica

E.4

Principal exclusion criteria

-age <50>80 yrs; incapability to give informed consent; -diabetes defined according to American Diabetes Association (ADA) criteria; -clinically significant liver or kidney dysfunction defined as s-ALT > 2 times upper reference or estimated creatinine-clearance (eGFR) < 60 mL / min/1.73m2, assessed by with CKD-EPI formula ( ); endocrinological diseases other than well controlled hypothyroidism, - personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia (MEN) syndrome, severe gastro-intestinal diseases (i.e gastroparesis, dumping syndromes),- current or history of chronic or acute pancreatitis; - any contraindication to the use of exenatide as per the Summary of Product Characteristics;- known abuse of alcohol or drugs; - ferro-magnetic prosthesis, - pacemaker or other metals incorporated in the body;- significant neurologic disease other than MCI (i.e. Parkinson's disease, multiple system atrophy, normal pressure hydrocephalus, progressive supranuclear palsy, subarachnoid hemorrhage, brain neoplasms, Huntington disease, epilepsy or head trauma);- BMI =22 Kg/m2 in subject = 70 yrs, MRI/CT showing unambiguous etiological evidence of cerebrovascular disease with regard to MCI; - severe sensory defects; - current presence of clinically significant psychiatric disorder;- warfarin treatment, clinically significant systemic condition; - history of cancer within the last 5 yrs; - known allergy to exenatide or any of the other components.

• età <50>80 anni:
• incapacità di fornire il consenso informato;
• diabete definito secondo i criteri dell’ American Diabetes Association (ADA)
• alterazioni epatiche (valori di transaminasi >2 volte rispetto ai limiti) o renali (GFR <60 ml/min con la formula di CKFD-EPI)
• storia pregressa o attuale di pancreatite
• qualsiasi controindicazione all’utilizzo di exenatide come da scheda tecnica del farmaco
• abuso di sostanze alcoliche o di droghe
• pacemaker or protesi metalliche che controindichino l’esecuzione della RMN
• evidenze alla RMN/TAC che suggeriscono una alterazione cerebrovascolare alla base della MCI
• difetti sensoriali severi
• presenza di disordini psichiatrici severi
• storia di patologia tumorale
• patologie endocrine ad eccezione di ipotiroidismo ben compensato con la terapia; storia personale o familiare di carcinoma midollare della tiroide o MEN
• patologie gastrointestinali severe quali gastroparesi o dumping syndorme
• patologie neurologiche quali Parkinson, idrocefalo, sclerosi multipla, tumori cerebrali, trauma cranico, epilessia, corea di Huntington, paralisi sopranucleare progressiva ed emorragia subaracnoidea,
• BMI =22 kg/m2 in soggetti con età > 70 anni
• allergia nota ad exenatide o ad uno dei suoi componenti
• terapia anticoagulante con warfarin

E.5 End points

E.5.1

Primary end point(s)

Improvement of ADAS-cog Alzheimer’s Disease Assessment Scale defined as absolute and percent change of ADAS-cog score at 16 (V2) and at 32 weeks (V3) after randomization compared to baseline. This test is recommended for second stage or more detailed assessments and/or for research evaluations. The ADAS-Cog consists of 7 performance items and 4 clinician-rated items covering memory, orientation, language and praxis. The total score is a sum of that obtained in each single task of the ADAS-Cog. Scores range from 70 (severe impairment) to 0 (no impairment).

miglioramento dell’ADAS-cog Alzheimer disease assessment scale definito come cambiamento percentuale ed assoluto dello score a 16 (V2) e a 32 settimane (V3) rispetto alla valutazione basale. Questo test è utilizzato come sistema valutativo di secondo livello ai fini di ricerca. Consiste nella valutazione di 7 aree riguardanti la memoria, l’orientamento, il linguaggio e la prassi. Il punteggio varia da 70 (alterazioni severe) fino a 0 (nessuna alterazione).

E.5.1.1

Timepoint(s) of evaluation of this end point

at 16 and 32 weeks after randomization compared to baseline

Alla 16 e 32 settimana rispetto alla misurazione basale

E.5.2

Secondary end point(s)

1. Pharmacodynamics by assessing absolute change in metabolic (fasting glycemia and HbA1C) and hormonal hormone profile levels (insulin and active GLP-1) .at 16 (V2) and at 32 weeks (V3) compared to baseline.
2. Improvements in other cognitive functions tests namely,
¿ Mini Mental State Evaluation (MMSE) and the quality score of MMSE , Phonemic verbal fluency test ; Semantic verbal fluency test ; Geriatric Depression Scale (GDS); Clinical Dementia Rating Scale (CDR); Neuropsychiatric Inventory (NPI); Activities of Daily Living (ADL); Instrumental Activities of Daily Living (IADL) measured as absolute and percent change in each test score at 16 (V2) and at 32 weeks (V3) compared to baseline
3. Absolute and percent change of each acquisition modality of connectivity of brain networks as assessed by functional MRI (fMRI) at 16 (V2) and at 32 weeks (V3) compared to baseline.

- Farmacodinamica valutando il cambiamento assoluto nei profilo metabolico (glicemia, HbA1C) ed ormonale (insulinemia, glucagonemia, GLP-1 attivo) a 16 (V2) e a 32 settimane (V3) rispetto alla valutazione basale
- Miglioramento nello score degli altri test di funzione cognitiva: Mini Mental State Evaluation (MMSE) and the quality score of MMSE, Phonemic verbal fluency test; Semantic verbal fluency test; Geriatric Depression Scale (GDS); Clinical Dementia Rating Scale (CDR); Neuropsychiatric Inventory (NPI); Activities of Daily Living (ADL); Instrumental Activities of Daily Living (IADL).
- Cambiamento percentuale ed assoluto di ciascuna modalit¿ di acquisizione del connettoma valutato mediante la RMI funzionale a 16 (V2) e a 32 settimane (V3) rispetto alla valutazione basale.

E.5.2.1

Timepoint(s) of evaluation of this end point

at 16 and 32 weeks after randomization compared to baseline

Alla 16 e 32 settimana rispetto alla misurazione basale

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

NESSUN TRATTAMENTO

NO TREATMENT

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.8.4.1

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

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

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

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)

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

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

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)

USUAL CARE

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

2015-09-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-07-14

P. End of Trial
P.	End of Trial Status	Ongoing

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