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Efficacy and Safety of ChOline ALfoscerate in Patient With Mild to Moderate Alzheimer's Disease (COALA)

Primary Purpose

Alzheimer Disease

Status
Recruiting
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Choline Alfoscerate 400mg
Placebo
Sponsored by
Daewoong Bio Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Changwon Fatima HospitalRecruiting
  • Gachon University Gil Medical CenterRecruiting
  • CHA Bundang Medical CenterRecruiting
  • The Catholic University of Korea Seoul ST.MARY'S Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Choline Alfoscerate 1,200mg + Donepezil 5mg or 10mg

Placebo + Donepezil 5mg or 10mg

Arm Description

Oral administration of choline alfoscerate 400mg TID, donepezil QD (evening) for 48 weeks, no dosage change during trial period

Oral administration of placebo TID, donepezil QD (evening) for 48 weeks, no dosage change during trial period

Outcomes

Primary Outcome Measures

Changes in ADAS-Cog scores
ADAS-cog change at 12 and 24 weeks from baseline Changes in ADAS-Cog scores at 48 weeks from baseline

Secondary Outcome Measures

Changes in ADAS-Cog scores
Changes in ADAS-Cog scores at 12, 24 weeks from baseline
Changes in ADCOMS scores
Changes in ADCOMS scores at 12, 24 and 48 weeks from baseline
Changes in K-IADL scores
Changes in K-IADL scores at 12, 24 and 48 weeks from baseline
Changes in CDR-SB scores
Changes in CDR-SB scores at 12, 24 and 48 weeks from baseline
Changes in K-MMSE-2 scores
Changes in K-MMSE-2 scores at 12, 24 and 48 weeks from baseline

Full Information

First Posted
December 6, 2021
Last Updated
May 16, 2022
Sponsor
Daewoong Bio Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05383183
Brief Title
Efficacy and Safety of ChOline ALfoscerate in Patient With Mild to Moderate Alzheimer's Disease
Acronym
COALA
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 13, 2022 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
December 9, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Daewoong Bio Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to determine whether combination of donepezil, a cholinesterase inhibitor, with choline alfoscerate has a more favourable clinical profile than monotherapy with donepezil alone.
Detailed Description
Aging population is a characteristic feature of demographic trends in developed countries. Hence, Alzheimer's disease is recognized as one of today's major healthcare challanges, and its significance will increase even more as the longevity of the population increases. Pre-clinical investigations have suggested that association between ChE-Is (cholinesterase inhibitors) and the cholinergic precursor choline alfoscerate enhances cholinergic neurotransmission more effectively than single compounds alone. This clinical trial is designed to assess if combination of the ChE-I donepezil with choline alfoscerate has a more favorable clinical profile than monotherapy with donepezil alone.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
630 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Choline Alfoscerate 1,200mg + Donepezil 5mg or 10mg
Arm Type
Experimental
Arm Description
Oral administration of choline alfoscerate 400mg TID, donepezil QD (evening) for 48 weeks, no dosage change during trial period
Arm Title
Placebo + Donepezil 5mg or 10mg
Arm Type
Placebo Comparator
Arm Description
Oral administration of placebo TID, donepezil QD (evening) for 48 weeks, no dosage change during trial period
Intervention Type
Drug
Intervention Name(s)
Choline Alfoscerate 400mg
Intervention Description
Oral administration
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral administration
Primary Outcome Measure Information:
Title
Changes in ADAS-Cog scores
Description
ADAS-cog change at 12 and 24 weeks from baseline Changes in ADAS-Cog scores at 48 weeks from baseline
Time Frame
48 weeks from baseline
Secondary Outcome Measure Information:
Title
Changes in ADAS-Cog scores
Description
Changes in ADAS-Cog scores at 12, 24 weeks from baseline
Time Frame
Time Frame: 12, 24 weeks from baseline
Title
Changes in ADCOMS scores
Description
Changes in ADCOMS scores at 12, 24 and 48 weeks from baseline
Time Frame
12, 24, and 48 weeks from baseline
Title
Changes in K-IADL scores
Description
Changes in K-IADL scores at 12, 24 and 48 weeks from baseline
Time Frame
12, 24, and 48 weeks from baseline
Title
Changes in CDR-SB scores
Description
Changes in CDR-SB scores at 12, 24 and 48 weeks from baseline
Time Frame
12, 24, and 48 weeks from baseline
Title
Changes in K-MMSE-2 scores
Description
Changes in K-MMSE-2 scores at 12, 24 and 48 weeks from baseline
Time Frame
12, 24, and 48 weeks from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: <Screening Inclusion Criteria> 50 ≤ Age ≤ 85 at time of screening 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 10 ≤ K-MMSE-2 score ≤ 26 at time of screening 0.5 ≤ CDR score ≤ 2 at time of screening Administration of donepezil 5 mg or 10 mg without dose change for at least 3 months at time of screening Ability to walk or to move using a walking aid (i.e. senior walker, cane, or wheelchair) 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 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) Voluntarily decision to participate in this clinical trial from both the subject and the subject's legal representative <Randomization Inclusion Criteria> 10 ≤ K-MMSE-2 score ≤ 26 at time of randomization Compliance with donepezil ≥ 80% during run-in Exclusion Criteria: <Screening Exclusion Criteria> 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 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 ≤ New Rating Scale for ARWMC (Age-Related White Matter Changes) score within 12 months of screening 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) Serious mental disorders such as severe depression, schizophrenia, alcoholism, and drug dependence 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 Genetic problems such as galactose intolerance, lapp lactase deficiency or glucose galactose malabsorption Gastrointestinal diseases (inflammatory bowel disease, etc.) that may affect the absorption of clinical investigational drugs Administration of other dementia treatments (galantamine, rivastigmine, memantine) than donepezil within 3 months of screening Administration of brain function improving drugs (citicoline, oxiracetam, piracetam, choline alfoscerate, Nicergoline, Nimodipine, ginko-biloba, acetyl-l carnitine, etc.) within 1 month of screening 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 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 Hypersensitivity to clinical investigational drugs (choline alfoscerate, donepezil), its components, or piperidine derivatives Possibility of dementia due to abnormalities in vitamin B12, folic acid, and thyroid stimulating hormone (TSH) levels 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) Uncontrolled hypertension (SBP>180 mmHg) Illitera Pregnancy and lactation 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yunjae Ahn
Phone
+82-550-8191
Email
yjahn@daewoong-bio.co.kr
Facility Information:
Facility Name
Changwon Fatima Hospital
City
Changwon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jay-Cheol Kwon
Facility Name
Gachon University Gil Medical Center
City
Incheon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ki Hyung Park
Facility Name
CHA Bundang Medical Center
City
Seongnam
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hyun Sook Kim
Facility Name
The Catholic University of Korea Seoul ST.MARY'S Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong-Won Yang, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of ChOline ALfoscerate in Patient With Mild to Moderate Alzheimer's Disease

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