Multicenter, randomized, double-blind, and placebo-controlled clinical trial to assess the efficacy and safety of donepezil versus placebo in mild cognitive impairment associated with Parkinson's disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Sep 2023 → ongoing

Decision date (initial)

2024-06-12

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-510959-35-00

EudraCT number

2022-001751-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Assessing the safety and efficacy on cognitive performance of donepezil over 12 months

Secondary objectives 5

1. Evaluate the effects of donepezil administered over 12 months on various cognitive tests and domains by analyzing changes in Trail Making Test A (TMT-A), Digit Span forward (DSd), Trail Making Test B (TMT-B), Phonemic Fluency (FF), Reduced Boston Naming Test (BNTr), Semantic Fluency (FS), Free and Cued Selective Reminding Test (FCSRT), Rey-Osterrieth Complex Figure Test (ROCF), recall of ROCF (rROCF), and Judgment of Line Orientation (JLO) from baseline to 12 months.
2. Assess the effects of donepezil administered over 12 months on anxiety, depression, apathy, psychosis, sleep, and autonomic dysfunction by analyzing changes in the Hospital Anxiety and Depression Scale (HADS), Starkstein Apathy Scale (AS), Neuropsychiatric Inventory (NPI), and MDS UPDRS parts I and II from baseline to 12 months.
3. Examine the impact of donepezil administered over 12 months on quality of life by analyzing changes in the Schwab & England Scale (S&E) and 8-item Parkinson's Disease Questionnaire (PDQ-8) from baseline to 12 months.
4. Evaluate the effects of donepezil administered over 12 months on the severity and overall clinical status of the patient by analyzing changes in the Clinical Global Impressions-Severity of Illness scale (CGI-S) and CGI-Global Improvement (CGI-I) from baseline to 12 months.
5. Assess the effects of donepezil administered over 12 months on subjective cognitive status by analyzing changes in the Patient Global Impression of Change scale (PGIC) from baseline to 12 months.

Conditions and MedDRA coding

Parkinson's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age between 50 and 80 years (inclusive).
2. Diagnosis of Parkinson's disease based on MDS criteria
3. Neuroimaging compatible with Parkinson's disease
4. Hoehn and Yahr stage (H&Y) I-III (inclusive).
5. Persistent subjective cognitive complaints in the 6 months prior to screening.
6. Diagnosis of Parkinson's disease-related mild cognitive impairment (PD-MCI) according to MDS PD-MCI criteria: Level I: MoCA ≤24 and ≥20(46) and Level II: 2/10 neuropsychological tests altered with a cutoff of 1.5 Standard Deviations(47,48).
7. Duration of PD-MCI for at least 3 months prior to screening.
8. Stable dopaminergic treatment in the 4 weeks prior to screening.

Exclusion criteria 13

1. Criteria for dementia associated with Parkinson's disease
2. Severe motor complications (moderate to severe motor fluctuations defined as a score >1 on item 42 of Part IV of the MDS UPDRS; or disabling dyskinesias defined as a score >1 on item 36 of Part IV of the MDS UPDRS).
3. History of Deep Brain Stimulation.
4. Active psychosis or treatment with antipsychotic medications, major hallucinations, HADS score ≥11, active impulse control disorder, or other severe active behavioral disorders.
5. Active treatment with anticholinergics, acetylcholinesterase inhibitors, or other systemic cholinergic enhancers, neuroleptics, potent CYP3A4 or 2D6 inhibitors, enzyme inducers, or drugs prolonging the QTc interval (see section 6.7).
6. Hypersensitivity or intolerance to donepezil, piperidine derivatives, lactose, or any of the excipients of the active drug.
7. History or impression, at the investigator's discretion, of poor therapeutic compliance.
8. Unstable medical or surgical condition, or life expectancy of <1 year.
9. Brain condition that may contribute to cognitive decline (history of stroke, brain tumor, neurosurgical intervention, etc.), including the presence of grade III leukoaraiosis on brain neuroimaging.
10. Insufficient proficiency in Spanish or the local language, illiteracy, sensory impairments (vision, hearing), legal incapacity, or any other mental, physical, or social condition that impedes giving informed consent or completing assessments adequately.
11. History of symptomatic orthostatic hypotension.
12. Pregnancy, desire for conception, refusal to use appropriate contraceptives during the study period and up to 6 months after, or lactation (see section 9.6).
13. Any significant abnormalities in medical history, examination, vital signs, laboratory tests, or ECG that, at the investigator's discretion, contraindicate participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Parkinson's Disease-Cognitive Rating Scale (PD-CRS)
2. Parkinson's Disease-Cognitive Functional Rating Scale (PD-CFRS)

Secondary endpoints 17

1. Trail Making Test A (TMT-A)
2. Digit Span directo (DSd)
3. Trail Making Test B (TMT-B)
4. Phonemic fluency
5. Boston Nomination Test reduced (BNTr)
6. Semantic fluency
7. Free and Cued Selective Reminding Test (FCSRT)
8. Figura compleja de Rey-Osterrieth (ROCF) y recuerdo de ROCF (rROCF)
9. Judgement of Line Orientation (JLO)
10. Hospital Anxiety and Depression Scale (HADS)
11. Starkstein Apathy Scale (AS)
12. Neuropsychiatric Inventory (NPI)
13. MDS UPDRS-I y -II
14. Schwab & England scale (S&E):
15. 8-item Parkinson’s Disease Questionnaire (PDQ-8)
16. Clinical Global Impressions (CGI-S y CGI-I)
17. Patients Global Impression of Change (PGIC)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Sponsor organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Address

Calle De San Quintin 77-79

City

Barcelona

Postcode

08041

Country

Spain

Scientific contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

UICEC Sant Pau

Public contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

UICEC Sant Pau

Locations

1 EU/EEA country · 21 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 4 files

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

Application history

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