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A Phase 2 Clinical Study to Explore the Optimal Dosage/Administration of PM012 Tablet in Alzheimer's Disease (PM012-2b)

Primary Purpose

Mild Alzheimer Disease

Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
PM012
PM012 Placebo
Donepezil
Donepezil placebo
Sponsored by
Mediforum Ltd., Co.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Alzheimer Disease focused on measuring Alzheimer's Disease, Dementia, Brain Diseases, Central Nervous System Disease, Nervous System Disease

Eligibility Criteria

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

Inclusion Criteria: 1) Male and female patients aged ≥ 50 and ≤ 85 years. 2) Patients clinically diagnosed as probable Alzheimer's disease based on DSM-IV and NINCDS-ADRDA criteria. 3) Patients between MMSE score of 20~26 at screening visit. 4) Patients with Global CDR score of 0.5 or 1 at the screening visit. 5) Patients administered with donepezil 5㎎ stably for over 3 months or who have never been administered donepezil. 6) Patients who can perform cognitive or other necessary tests. 7) Patients who have a caretaker who can accompany the patient for all clinical visits and for the primary efficacy evaluation (a caretaker is a family member or someone trustworthy who provides care for daily activities, spending more than 8 hours per week with patients). 8) Patients who have consented to participate in medically acceptable contraception* * Effective contraception methods: Infertility surgery of the patient or his/her spouse (vasectomy, tubal ligation), placement of an intrauterine contraceptive device, double barrier method (concomitant use of spermicides and condoms, and contraceptive diaphragms, vaginal sponges, or cervical caps). Oral contraceptives and intermittent celibacy (absolute celibacy is allowed) are not acknowledged as effective contraceptive methods. 9) Patients who have signed the informed consent on his/her own will Exclusion Criteria: 1) Patients with hypersensitivity to the investigational product or components contained in the investigational product. 2) Patients with hypersensitivity to piperidine derivatives. 3) Patients with possible, probable or definite vascular dementia according to the NINDS-AIREN criteria. 4) History (cerebrovascular disease, structural or developmental malformations, epilepsy, contagious, degenerative, or infectious/demyelinating CNS status) and/or evidence (CT or MRI results performed at screening or within 12 months) of other CNS diseases as the major cause of dementia. 5) Patients who are illiterate. 6) Patients with severe hearing or visual disabilities so that efficacy assessment is impossible. 7) Abnormal test results for vitamin B12, serologic testing for syphilis, or thyroid stimulating hormone (TSH) that may have contributed to or may be the cause of patient's dementia. 8) Patients with a history of significant psychiatric disease such as schizophrenia or bipolar disorder that may interfere with participation in the trial as viewed by the investigator, or patients with current major depression disorder (Short Form GDS ≥ 7) (However, patients who depressed due to Alzheimer's disease can participate in this trial by the investigator). 9) Patients with genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 10) Patients with a history of known or suspected seizure including febrile seizure, or recent history of loss of consciousness or a history of significant head trauma with loss of consciousness. 11) Patients with gastrointestinal, endocrinological, or cardiovascular disorders that is not controlled by diet or drugs. 12) Patients with cardiac diseases such as myocardial infarction, valvular heart disease, or arrhythmia within 3 months prior to screening. 13) Patients with asthma or obstructive pulmonary diseases that is not controlled by drugs. 14) Patients with extrapyramidal disorders (Parkinson's disease, Parkinsonism, etc). 15) Patients with dementia due to Creutzfeldt-Jakob disease, Pick's disease, or Huntington's disease. 16) Patients with uncontrolled diabetes (HbA1c > 8.0%) or insulin dependent diabetes. 17) Patients with a history of alcohol or other substance abuse. 18) Patients with hypertension with systolic pressure over 165mmHg or diastolic pressure over 96mmHg. 19) Patients with severe renal dysfunction (Serum creatinine over 2.0㎎/dl). 20) Patients with severe liver dysfunction (ALT, AST, total bilirubin more than 2.5-fold the upper normal limit). 21) Patient who has been administered drugs that Dementia drugs(Donepezil, Galantamine, Memantine, Rivastigmine tartrate) within 3 months prior to screening (However, patients who have been administered donepezil 5mg stably for over 3 months are excluded). 22) Patient who has required to take restricted drugs other than investigational products during the clinical trial period. 23) patient who has unabled to take concomitant drugs during the clinical trial period under the following conditions : It was taken without dose change 2 months before randomization, and was taken without dose change during the clinical trial period (except for drugs allowed to be taken as needed). 24) Patients with a history of clinically significant drug hypersensitivity reaction. 25) Patients who have been administered investigational products from another clinical trial within 3 months prior to participation in this trial. 26) Patients who are deemed unfit to participate in this trial by the investigator.

Sites / Locations

  • MediforumRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Arm Label

Aricept 5 mg

PM012 2,600 mg

PM012 3,900 mg

PM012 5,200 mg

Arm Description

Aricept 5 mg + Placebo of PM012 eight tablets, daily during 12 weeks (oral)

PM012 2,600 mg + Placebo of PM012 four tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)

PM012 3,900 mg + Placebo of PM012 two tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)

PM012 5,200 mg + Placebo of Aricept one tablet, daily during 12 weeks (oral)

Outcomes

Primary Outcome Measures

ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)
To compare the efficacy of dose groups and active comparator group based on cognitive functions assessed through ADAS-cog at 12 weeks post-dose. The total score ranges from 0 (no function) to 70 (maximal function), and the higher the score, the greater the cognitive impairment.
ADCS-MCI-ADLI (Alzheimer's Disease Cooperative Study-Mild Cognitive Impairment- Activities of Daily Living Inventory)
To compare the efficacy of dose groups and active comparator group based on activities of daily living assessed through ADCS-MCI-ADLI at 12 weeks post-dose The total score ranges from 0 to 53, and the lower the score, the more the participant needs help with daily living.

Secondary Outcome Measures

ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)
To compare the efficacy of dose groups and active comparator group based on cognitive functions assessed through ADAS-cog at 8 weeks post-dose. The total score ranges from 0 (no function) to 70 (maximal function), and the higher the score, the greater the cognitive impairment.
ADCS-MCI-ADLI (Alzheimer's Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living Inventory)
To compare the efficacy of dose groups and active comparator group based on activities of daily living assessed through ADCS-MCI-ADLI at 8 weeks post-dose. The total score ranges from 0 to 53, and the lower the score, the more need to help with daily living.
CDR (Clinical Dementia Rating)
To compare the efficacy of dose groups and active comparator group based on overall function assessed through CDR at 8 weeks and 12 weeks post-dose. Scores are on a scale of 0 - 5, with 0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia, 4 = profound dementia, and 5 = terminal dementia.
MMSE (Mini Mental State Examination)
To compare the efficacy of dose groups and active comparator group based on cognitive functions assessed through MMSE at 8 weeks and 12 weeks post-dose. The total score ranges from 0 to 30 and the lower the score, the more the cognitive problems.
NPI (Neuropsychiatric Inventory)
To compare the efficacy of dose groups and active comparator group based on behavioral change assessed through NPI at 8 weeks and 12 weeks post-dose. The total score ranges from 0 to 144 and the higher the score, the more neuropsychiatric symptoms.
Number of participants with adverse events, with abnormal physical exam findings and abnormal laboratory tests results.
- To compare the safety of dose groups and active comparator group based on adverse events and clinical laboratory tests at 12 weeks post-dose.

Full Information

First Posted
March 17, 2023
Last Updated
April 13, 2023
Sponsor
Mediforum Ltd., Co.
Collaborators
LSK Global Pharma Services Co. Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05811000
Brief Title
A Phase 2 Clinical Study to Explore the Optimal Dosage/Administration of PM012 Tablet in Alzheimer's Disease
Acronym
PM012-2b
Official Title
A Phase 2 Clinical Study to Explore the Optimal Dosage/Administration of PM012 Tablet in Alzheimer's Disease: Double-Blind, Randomized Between Placebo Control Group and Dose Groups, Parallel-Design, Multicenter Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 27, 2020 (Actual)
Primary Completion Date
February 24, 2021 (Actual)
Study Completion Date
August 13, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mediforum Ltd., Co.
Collaborators
LSK Global Pharma Services Co. Ltd.

4. Oversight

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

5. Study Description

Brief Summary
To evaluate the safety and efficacy of PM012 tablets for Alzheimer's disease, dose-finding study will be performed on phase 2b, and the established dose will be used for the non-inferiority phase 3 trial to evaluate the investigational product's safety and efficacy: Double blind, randomized, active drug comparative, multi-center, parallel-group clinical trial
Detailed Description
This study is to establish an effective therapeutic dose in Korean patients with a mild degree of Alzheimer's disease, by comparing the safety and efficacy of the investigational product PM012 tablet administered to the 2,600 mg /day group, 3,900 mg /day group, and 5,200 mg /day group, with the active drug Aricept 5 mg (donepezil hydrochloride) from Daewoong Pharmaceuticals administered to the active control group, for 12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Alzheimer Disease
Keywords
Alzheimer's Disease, Dementia, Brain Diseases, Central Nervous System Disease, Nervous System Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
312 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Aricept 5 mg
Arm Type
Active Comparator
Arm Description
Aricept 5 mg + Placebo of PM012 eight tablets, daily during 12 weeks (oral)
Arm Title
PM012 2,600 mg
Arm Type
Experimental
Arm Description
PM012 2,600 mg + Placebo of PM012 four tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Arm Title
PM012 3,900 mg
Arm Type
Experimental
Arm Description
PM012 3,900 mg + Placebo of PM012 two tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Arm Title
PM012 5,200 mg
Arm Type
Experimental
Arm Description
PM012 5,200 mg + Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention Type
Drug
Intervention Name(s)
PM012
Intervention Description
PM012 650 mg tablet drug
Intervention Type
Drug
Intervention Name(s)
PM012 Placebo
Intervention Description
PM012 tablet placebo
Intervention Type
Drug
Intervention Name(s)
Donepezil
Intervention Description
Aricept 5 mg (donepezil hydrochloride) drug
Intervention Type
Drug
Intervention Name(s)
Donepezil placebo
Intervention Description
Aricept 5 mg (donepezil hydrochloride) placebo
Primary Outcome Measure Information:
Title
ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)
Description
To compare the efficacy of dose groups and active comparator group based on cognitive functions assessed through ADAS-cog at 12 weeks post-dose. The total score ranges from 0 (no function) to 70 (maximal function), and the higher the score, the greater the cognitive impairment.
Time Frame
At 12 weeks post-dose
Title
ADCS-MCI-ADLI (Alzheimer's Disease Cooperative Study-Mild Cognitive Impairment- Activities of Daily Living Inventory)
Description
To compare the efficacy of dose groups and active comparator group based on activities of daily living assessed through ADCS-MCI-ADLI at 12 weeks post-dose The total score ranges from 0 to 53, and the lower the score, the more the participant needs help with daily living.
Time Frame
At 12 weeks post-dose
Secondary Outcome Measure Information:
Title
ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)
Description
To compare the efficacy of dose groups and active comparator group based on cognitive functions assessed through ADAS-cog at 8 weeks post-dose. The total score ranges from 0 (no function) to 70 (maximal function), and the higher the score, the greater the cognitive impairment.
Time Frame
At 8 weeks post-dose
Title
ADCS-MCI-ADLI (Alzheimer's Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living Inventory)
Description
To compare the efficacy of dose groups and active comparator group based on activities of daily living assessed through ADCS-MCI-ADLI at 8 weeks post-dose. The total score ranges from 0 to 53, and the lower the score, the more need to help with daily living.
Time Frame
At 8 weeks post-dose
Title
CDR (Clinical Dementia Rating)
Description
To compare the efficacy of dose groups and active comparator group based on overall function assessed through CDR at 8 weeks and 12 weeks post-dose. Scores are on a scale of 0 - 5, with 0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia, 4 = profound dementia, and 5 = terminal dementia.
Time Frame
At 8 weeks and 12 weeks post-dose
Title
MMSE (Mini Mental State Examination)
Description
To compare the efficacy of dose groups and active comparator group based on cognitive functions assessed through MMSE at 8 weeks and 12 weeks post-dose. The total score ranges from 0 to 30 and the lower the score, the more the cognitive problems.
Time Frame
At 8 weeks and 12 weeks post-dose
Title
NPI (Neuropsychiatric Inventory)
Description
To compare the efficacy of dose groups and active comparator group based on behavioral change assessed through NPI at 8 weeks and 12 weeks post-dose. The total score ranges from 0 to 144 and the higher the score, the more neuropsychiatric symptoms.
Time Frame
At 8 weeks and 12 weeks post-dose
Title
Number of participants with adverse events, with abnormal physical exam findings and abnormal laboratory tests results.
Description
- To compare the safety of dose groups and active comparator group based on adverse events and clinical laboratory tests at 12 weeks post-dose.
Time Frame
At 12 weeks post-dose

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: 1) Male and female patients aged ≥ 50 and ≤ 85 years. 2) Patients clinically diagnosed as probable Alzheimer's disease based on DSM-IV and NINCDS-ADRDA criteria. 3) Patients between MMSE score of 20~26 at screening visit. 4) Patients with Global CDR score of 0.5 or 1 at the screening visit. 5) Patients administered with donepezil 5㎎ stably for over 3 months or who have never been administered donepezil. 6) Patients who can perform cognitive or other necessary tests. 7) Patients who have a caretaker who can accompany the patient for all clinical visits and for the primary efficacy evaluation (a caretaker is a family member or someone trustworthy who provides care for daily activities, spending more than 8 hours per week with patients). 8) Patients who have consented to participate in medically acceptable contraception* * Effective contraception methods: Infertility surgery of the patient or his/her spouse (vasectomy, tubal ligation), placement of an intrauterine contraceptive device, double barrier method (concomitant use of spermicides and condoms, and contraceptive diaphragms, vaginal sponges, or cervical caps). Oral contraceptives and intermittent celibacy (absolute celibacy is allowed) are not acknowledged as effective contraceptive methods. 9) Patients who have signed the informed consent on his/her own will Exclusion Criteria: 1) Patients with hypersensitivity to the investigational product or components contained in the investigational product. 2) Patients with hypersensitivity to piperidine derivatives. 3) Patients with possible, probable or definite vascular dementia according to the NINDS-AIREN criteria. 4) History (cerebrovascular disease, structural or developmental malformations, epilepsy, contagious, degenerative, or infectious/demyelinating CNS status) and/or evidence (CT or MRI results performed at screening or within 12 months) of other CNS diseases as the major cause of dementia. 5) Patients who are illiterate. 6) Patients with severe hearing or visual disabilities so that efficacy assessment is impossible. 7) Abnormal test results for vitamin B12, serologic testing for syphilis, or thyroid stimulating hormone (TSH) that may have contributed to or may be the cause of patient's dementia. 8) Patients with a history of significant psychiatric disease such as schizophrenia or bipolar disorder that may interfere with participation in the trial as viewed by the investigator, or patients with current major depression disorder (Short Form GDS ≥ 7) (However, patients who depressed due to Alzheimer's disease can participate in this trial by the investigator). 9) Patients with genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 10) Patients with a history of known or suspected seizure including febrile seizure, or recent history of loss of consciousness or a history of significant head trauma with loss of consciousness. 11) Patients with gastrointestinal, endocrinological, or cardiovascular disorders that is not controlled by diet or drugs. 12) Patients with cardiac diseases such as myocardial infarction, valvular heart disease, or arrhythmia within 3 months prior to screening. 13) Patients with asthma or obstructive pulmonary diseases that is not controlled by drugs. 14) Patients with extrapyramidal disorders (Parkinson's disease, Parkinsonism, etc). 15) Patients with dementia due to Creutzfeldt-Jakob disease, Pick's disease, or Huntington's disease. 16) Patients with uncontrolled diabetes (HbA1c > 8.0%) or insulin dependent diabetes. 17) Patients with a history of alcohol or other substance abuse. 18) Patients with hypertension with systolic pressure over 165mmHg or diastolic pressure over 96mmHg. 19) Patients with severe renal dysfunction (Serum creatinine over 2.0㎎/dl). 20) Patients with severe liver dysfunction (ALT, AST, total bilirubin more than 2.5-fold the upper normal limit). 21) Patient who has been administered drugs that Dementia drugs(Donepezil, Galantamine, Memantine, Rivastigmine tartrate) within 3 months prior to screening (However, patients who have been administered donepezil 5mg stably for over 3 months are excluded). 22) Patient who has required to take restricted drugs other than investigational products during the clinical trial period. 23) patient who has unabled to take concomitant drugs during the clinical trial period under the following conditions : It was taken without dose change 2 months before randomization, and was taken without dose change during the clinical trial period (except for drugs allowed to be taken as needed). 24) Patients with a history of clinically significant drug hypersensitivity reaction. 25) Patients who have been administered investigational products from another clinical trial within 3 months prior to participation in this trial. 26) Patients who are deemed unfit to participate in this trial by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dai Won Yoo
Phone
+82.10.9412.9189
Email
stiger9189@gmediforum.com
Facility Information:
Facility Name
Mediforum
City
Seoul
State/Province
Seongdon-gu
ZIP/Postal Code
04784
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dai Won Yoo
Phone
+82.10.9412.9189
Email
stiger9189@gmediforum.com

12. IPD Sharing Statement

Links:
URL
https://pubmed.ncbi.nlm.nih.gov/22458507/
Description
Safety and efficacy assessment of standardized herbal formula PM012
URL
https://pubmed.ncbi.nlm.nih.gov/26446019/
Description
Standardized Herbal Formula PM012 Decreases Cognitive Impairment and Promotes Neurogenesis in the 3xTg AD Mouse Model of Alzheimer's Disease

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A Phase 2 Clinical Study to Explore the Optimal Dosage/Administration of PM012 Tablet in Alzheimer's Disease

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