CHOLINE-2 - Donepezil Versus Non-drug Treatment in Alzheimer's Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

10 Feb 2022 → ongoing

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ASSOCIATION FRANCE ALZHEIMER ET MALADIES APPARENTEES

External identifiers

EU CT number

2024-515038-34-00

EudraCT number

2021-001788-26

ClinicalTrials.gov

NCT04661280

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the cognitive efficiency at 6 months of daily intake of
donepezil compared to the usual non-drug management by course of
treatment.

Secondary objectives 1

1. Efficacy at 6 months on the different clinical scales used: ADAS-Cog, CDR, ADCS-ADL, quality of life, ZARIT.

Conditions and MedDRA coding

Interest of adding donepezil to the non-medicinal care pathway recommended in France for Alzheimer's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Diagnosis of Alzheimer's disease according to the 2014 IWG-2 criteria.
2. Covered by social security.
3. Age ≥ 50 years old.
4. Lack of legal protection measure (guardianship, curatorship).
5. MMSE score ≥ 10 on inclusion.
6. Aβ42 in the CSF or abnormal Aβ40 / Aβ42 ratio according to the local cut-offs of the different centers.
7. Phosphorylated tau in the CSF abnormal according to the local cut-offs of the different centers.
8. Presence of a family companion or a person at home who can ensure compliance with treatment in the event of an MMSE score <20.
9. Sufficient command of the French language for the taking of neuropsychological tests.

Exclusion criteria 15

1. Other cause of major neurocognitive impairment.
2. Previous symptomatic treatment of Alzheimer's disease
3. Known hypersensitivity to donepezil hydrochloride or to any of the excipients listed in the SPC.
4. Cardiological contraindication after possible advice from a cardiologist, at the initiative of the investigator, including bradycardia, sinus disease or other supraventricular conduction abnormalities such as sinoauricular or atrioventricular block.
5. Family or personal history of QTc prolongation, or a Fridericiacorrected QT interval (QTcF) > 450 msec for men and > 470 msec for women.
6. Use of concomitant medications known to prolong the QTc interval,
7. History of relevant pre-existing cardiac pathology (e.g. uncompensated heart failure, recent myocardial infarction, bradyarrhythmias) or electrolyte disorders (hypokalaemia, hypomagnesaemia).
8. Patients at particular risk of ulceration, history of ulcer disease, or receiving concomitant treatment with non-steroidal anti-inflammatory drugs.
9. Patients at risk of urinary retention.
10. History of epileptic disease.
11. History of neuroleptic malignant syndrome
12. History of asthma or obstructive bronchopulmonary disease.
13. Severe hepatic impairment
14. Taking any of the following medications: > CYP3A4 inhibitors, such as ketonozale. > 2D6 inhibitors, such as quinidine. > CYP3A4 inhibitors such as itraconazole and erythromycin. > CYP2D6 inhibitors, such as fluoxetine. > Enzyme inducers such as rifampin, phenytoin, carbamazepine. > Class IA antiarrhythmics (e.g. quinidine); > Class III antiarrhythmics (e.g. amiodarone, sotalol). > Other antipsychotics (e.g. phenothiazine derivatives, sertindole, pimozide, ziprasidone). > Certain antibiotics (e.g. clarithromycin, erythromycin, levofloxacin, moxifloxacin).
15. Participation in other interventional research

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in MMSE score between inclusion and 6 months, in the arm treated with donepezil and the usual course of care arm.

Secondary endpoints 1

1. Difference at 6 months in scores, ADAS-Cog, CDR, ADCS-ADL, quality of life, ZARIT.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Julien DUMURGIER

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Julien DUMURGIER

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications