Combining donepezil with choline alfoscerate for Alzheimer's treatment

A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase IV Trial to Evaluate the Efficacy and Safety of Choline Alfoscerate in Patients With Mild to Moderate Alzheimer's Disease

This study is testing if combining donepezil with choline alfoscerate can help people with mild to moderate Alzheimer's disease feel better compared to just taking donepezil alone.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 630 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: Daewoong Bio Inc. (Industry-sponsored)
• Locations: 4 sites (Changwon and 3 other locations)
• Trial ID: NCT05383183 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the efficacy and safety of combining donepezil, a cholinesterase inhibitor, with choline alfoscerate in patients with mild to moderate Alzheimer's disease. The study will compare the clinical outcomes of this combination therapy against donepezil monotherapy. By enhancing cholinergic neurotransmission, the trial seeks to determine if the combination provides a more favorable clinical profile. Participants will be monitored for improvements in cognitive function and overall health.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 50 to 85 diagnosed with mild to moderate Alzheimer's disease who have been stable on donepezil for at least three months.

Not a fit: Patients with severe Alzheimer's disease or those not currently taking donepezil may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer improved cognitive function and quality of life for patients with Alzheimer's disease.

How similar studies have performed: Previous studies have shown promising results with cholinesterase inhibitors, but this specific combination approach is relatively novel.

Eligibility criteria

Inclusion Criteria:

\<Screening Inclusion Criteria\>

1. 50 ≤ Age ≤ 85 at time of screening
2. Diagnosed as a probable Alzheimer Dementia patient according to the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria
3. 10 ≤ K-MMSE-2 score ≤ 26 at time of screening
4. 0.5 ≤ CDR score ≤ 2 at time of screening
5. Administration of donepezil 5 mg or 10 mg without dose change for at least 3 months at time of screening
6. Ability to walk or to move using a walking aid (i.e. senior walker, cane, or wheelchair)
7. Presence of a caregiver who regularly spends time with the patient and can accompany the patient to hospital visits

   - The caregiver must spend at least 8 hours per week with the patient
   * The caregiver should be able to supervise trial compliance and report subject status to the investigator
8. Sufficient visual acuity, hearing, language ability, motor function and comprehension, as judged by the investigator, to follow the examination procedure (auxiliary devices such as glasses and hearing aids are permitted)
9. Voluntarily decision to participate in this clinical trial from both the subject and the subject's legal representative

\<Randomization Inclusion Criteria\>

1. 10 ≤ K-MMSE-2 score ≤ 26 at time of randomization
2. Compliance with donepezil ≥ 80% during run-in

Exclusion Criteria:

\<Screening Exclusion Criteria\>

1. Dementia due to other causes including:

   - Probable vascular dementia according to NINDS-AIREN criteria
   * Infection of the central nervous system (eg HIV, syphilis, etc.)
   * Head trauma
   * Creutzfeld-Jacob disease
   * Pixie's disease
   * Huntington's disease
   * Parkinson's disease
   * Drug addiction and/or Alcoholism
2. Patients with other major structural brain diseases (strategic cerebral infarction, subdural hematoma, traffic hydrocephalus, brain tumor) and/or evidence (CT or MRI results performed within the past 12 months or at screening) as the cause of dementia (provided that (Excluding lacunar cerebral infarction with a diameter of less than 1 cm in the area judged not to be related to cognitive function)
3. 3 ≤ New Rating Scale for ARWMC (Age-Related White Matter Changes) score within 12 months of screening
4. Myocardial infarction, unstable angina pectoris, orthostatic hypotension or unexplained syncope within 12 months of screening, hospitalization for arrhythmia, or moderate to severe congestive heart failure (NYHA class III or IV), clinically Patients with significant structural heart disease (valvular disease, hypertrophic cardiomyopathy)
5. Serious mental disorders such as severe depression, schizophrenia, alcoholism, and drug dependence
6. History of malignant tumor within 5 years of screening. (However, enrollment is allowed if any of the following applies:)

   * More than 5 years since completion of treatment for tumor
   * Basal cell carcinoma, squamous cell carcinoma of the skin, or prostate cancer
7. Genetic problems such as galactose intolerance, lapp lactase deficiency or glucose galactose malabsorption
8. Gastrointestinal diseases (inflammatory bowel disease, etc.) that may affect the absorption of clinical investigational drugs
9. Administration of other dementia treatments (galantamine, rivastigmine, memantine) than donepezil within 3 months of screening
10. Administration of brain function improving drugs (citicoline, oxiracetam, piracetam, choline alfoscerate, Nicergoline, Nimodipine, ginko-biloba, acetyl-l carnitine, etc.) within 1 month of screening
11. Administration of dementia treatments, brain function improving agents, central nervous system stimulants, anticholinergics, tricyclic antidepressants, classic antipsychotics, and hypnotics (excluding short-acting hypnotics) other than experimental drugs during trial period
12. Administration of atypical antipsychotics, anxiolytics, antidepressants (except tricyclic antidepressants), thyroid hormones, short-acting hypnotics, hormone replacement therapy, vitamin E, vitamin B12 supplements, antiparkinsonian drugs, and cholinergic drugs during trial period (However, enrollment is allowed if all of the following apply:)

    - Administration without any changes in dosage within 2 months of randomization

    - Administration without any changes in dosage during trial period

    - except for PRN drugs
13. Hypersensitivity to clinical investigational drugs (choline alfoscerate, donepezil), its components, or piperidine derivatives
14. Possibility of dementia due to abnormalities in vitamin B12, folic acid, and thyroid stimulating hormone (TSH) levels
15. Abnormalities in blood tests at screening:

    - Liver dysfunction: AST or ALT ≥ 3 times the upper limit of normal range

    - Renal dysfunction: Creatinine clearance\* \< 25 mL/min/1.73 m2

    \*MDRD Formula Creatinine clearance (mL/min/1.73m2)= 175 × {serum Creatinine (mg/dL)}- 1.154 × (Age)-0.203 × 0.742 (for female only)
16. Uncontrolled hypertension (SBP\>180 mmHg)
17. Illitera
18. Pregnancy and lactation
19. In case of a woman, a patient who does not fall under any of the following:

    * Menopause for at least 2 years at time of screening
    * Contraceptive through surgical methods
20. Deemed inappropriate for enrollment by the investigator for other reasons \<Randomization Exclusion Criteria\>

1) Abnormalities in blood tests at time of randomization

* Liver dysfunction: AST or ALT ≥ 3 times the upper limit of normal range
* Renal dysfunction: Creatinine clearance\* \< 25 mL/min/1.73 m2 \*MDRD Formula Creatinine clearance (mL/min/1.73m2)= 175 × {serum Creatinine (mg/dL)}- 1.154 × (Age)-0.203 × 0.742 (for female only) 2) Uncontrolled hypertension (SBP\>180 mmHg) at the time of randomization 3) Administration of other investigational drugs within the past 3 months from the time of randomization 4) Deemed inappropriate for enrollment by the investigator for other reasons

Where this trial is running

Changwon and 3 other locations

• Changwon Fatima Hospital — Changwon, Korea, Republic of (Recruiting)
• Gachon University Gil Medical Center — Incheon, Korea, Republic of (Recruiting)
• CHA Bundang Medical Center — Seongnam, Korea, Republic of (Recruiting)
• The Catholic University of Korea Seoul ST.MARY'S Hospital — Seoul, Korea, Republic of (Not_yet_recruiting)

Study contacts

• Study coordinator: Yunjae Ahn

Conditions Alzheimer Disease