Study to Explore the Optimal Dosage/Administration in Alzheimer's Disease

Study Overview
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Brief Summary
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The investigators intend to perform exploratory evaluation of the treatment effectiveness and safety of PM012 Tablet of PuriMED Co., Ltd. at 2 doses in Korean patients with mild to moderate dementia of Alzheimer's type. To achieve this, this study aims to compare each dose with placebo control for the efficacy and safety to explore the clinically optimal dose of PM012 Tablet for therapeutic confirmatory (phase 3) clinical studies.

Detailed Description
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Period of study -48 months from the date of KFDA approval of the protocol Study subjects -Patients with mild to moderate Alzheimer's disease Study objectives Primary objective To compare the efficacy of 2 doses of PM012 Tablet and placebo based on cognitive effect assessed by ADAS-cog at Week 12 post-dose Secondary objectives To compare the efficacy of 2 doses of PM012 Tablet and placebo based on cognitive effect assessed by ADAS-cog at Week 8 post-dose To compare the efficacy of 2 doses of PM012 Tablet and placebo based on overall functional effect assessed by CDR at Weeks 8 and 12 post-dose To compare the efficacy of 2 doses of PM012 Tablet and placebo based on activities of daily living assessed by K-IADL at Weeks 8 and 12 post-dose To compare the efficacy of 2 doses of PM012 Tablet and placebo based on behavioral changes assessed by NPI at Weeks 8 and 12 post-dose To compare the efficacy of 2 doses of PM012 Tablet and placebo based on cognitive effect assessed by K-MMSE at Weeks 8 and 12 post-dose To compare the efficacy of 2 doses of PM012 Tablet and placebo based on improvement on VAS assessed by Senile Dementia Pattern Identification Diagnosis System at Weeks 8 and 12 post-dose Study drug / Comparator -650-mg PM012 Tablet by PuriMED Co., Ltd. / Placebo Dosage/ Administration and Method of administration Placebo group Morning:Placebo 2T, Evening:Placebo 2T Dose group 1 Morning:Placebo 1T+Study drug 1T, Evening:Placebo 1T+Study drug 1T Dose group 2 Morning:Study drug 2T, Evening:Study drug 2T Study drug is 650-mg PM012 tablet The drug will be taken with water within 30 minutes after breakfast and supper. Even if no meal is taken, dosing will not be omitted and the drug should be taken with enough amount of water. Treatment duration -12 weeks Number of subjects placebo group Efficacy population:42, Drop-out(20%)included:53 Dose group 1 Efficacy population:42, Drop-out(20%)included:53 Dose group 2 Efficacy population:42, Drop-out(20%)included:53 Total Efficacy population:126, Drop-out(20%)included:159 Study method This study is designed to be a multicenter, randomized, double-blind, parallel placebo group and 2 dose groups, phase 2 clinical study in patients with dementia of Alzheimer's type aged ≥ 50 and ≤ 85 years. Once a subject voluntarily provides the written consent to participate in the study, he/she will be randomized only if meeting the inclusion criteria and exclusion criteria through screening test. Randomized subjects will receive the study drug or the placebo for 12 weeks.

Official Title
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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

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: PM012
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1)Male and female patients aged ≥ 50 and ≤ 85 years 2)Clinically diagnosed with probable Alzheimer's disease based on DSM-IV and NINCDS-ADRDA criteria 3)K-MMSE score of 12 26 at screening visit 4)For females: 2 years of confirmed menopause or surgical sterilization. 5)Able to walk (including the use of aids) 6)Able to perform procedures for cognitive and other tests 7)Residing with a life-long guardian willing to accompany the subject's on all visits, oversee his/her compliance with the procedures specified in the protocol and the study drug, and report his/her condition. 8)Having signed him/herself or his/her legally acceptable representative having signed the written informed consent form Exclusion Criteria: 1)Possible, probable, or definite vascular dementia by NINDS-AIREN criteria 2)History and/or evidence (result of CT or MRI performed within the past 12 months or at screening) of other CNS disease (cerebrovascular disease, structural or developmental anomaly, epilepsy, contagious, degenerative or infectious/demyelinating CNS condition) as a cause of dementia 3)Delusion, delirium, epilepsy and other neurological pathology on neurological examination 4)Abnormal test result on vitamin B12, syphilis serology, and thyroid stimulating hormone (TSH) tests that are thought to contribute to the subject's dementia severity or be a cause of dementia 5)History of significant psychiatric disease such as schizophrenia or bipolar affective disorder that may interfere with the participation in this study in the opinion of the investigator, or current depression (GDS ≥ 18) 6)Past history of known or suspected seizures including febrile convulsion, unexplained recent unconsciousness or past history of significant head trauma with unconsciousness. 7)Gastrointestinal, endocrine and cardiovascular disease not controlled by diet or pharmacologic therapy 8)Cardiac disease such as myocardial infarction or valvular disease of heart, arrhythmia within 3 months of the study start 9)Diabetes mellitus not controlled by hypoglycemic agent or insulin-dependent diabetes mellitus 10)Past history of alcohol or other drug abuse 11)Having taken acetylcholinesterase inhibitor or memantine within the past 3 months 12)Hypertension with systolic blood pressure of > 165 mmHg or diastolic blood pressure of > 96 mmHg 13)Severe renal impairment (serum creatinine ≥ 1.7 mg/dl) 14)Severe hepatic impairment (ALT, AST, or bilirubin ≥ 2.0 x upper limit of normal) 15)Is taking or expected to take disallowed concomitant medication 16)History of clinically significant drug hypersensitivity 17)Is ineligible to participate in this study in the judgment of the investigator

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group<br>• Drug : Placebo 2 tablet The drug will be taken with water within 30 minutes after breakfast and supper. Even if no meal is taken, dosing will not be omitted and the drug should be taken with enough amount of water. | Drug: Placebo<br>* The drug will be taken with water within 30 minutes after breakfast and supper. 650mg/1 tablet, PO, 12weeks<br>* Other names: Placebo (for PM012);|
| Experimental: Dose group 1<br>Drug : Placebo 1 tablet + Study drug 1 tablet Study drug(650-mg PM012 tablet) The drug will be taken with water within 30 minutes after breakfast and supper. Even if no meal is taken, dosing will not be omitted and the drug should be taken with enough amount of water. | Drug: PM012<br>* The drug will be taken with water within 30 minutes after breakfast and supper. 650mg/1 tablet, PO, 12weeks<br>* Other names: 650-mg PM012 tablet;Drug: Placebo<br>* The drug will be taken with water within 30 minutes after breakfast and supper. 650mg/1 tablet, PO, 12weeks<br>* Other names: Placebo (for PM012);|
| Experimental: Dose group 2<br>Drug : Study drug 2 tablet Study drug (650-mg PM012 tablet) The drug will be taken with water within 30 minutes after breakfast and supper. Even if no meal is taken, dosing will not be omitted and the drug should be taken with enough amount of water. | Drug: PM012<br>* The drug will be taken with water within 30 minutes after breakfast and supper. 650mg/1 tablet, PO, 12weeks<br>* Other names: 650-mg PM012 tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAS-cog | * To compare the efficacy of 2 doses of PM012 Tablet and placebo based on cognitive effect assessed by ADAS-cog at Week 12 post-dose | Week 12 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAS-cog | * To compare the efficacy of 2 doses of PM012 Tablet and placebo based on cognitive effect assessed by ADAS-cog at Week 8 post-dose | Weeks 8 post-dose | 
| CDR | * To compare the efficacy of 2 doses of PM012 Tablet and placebo based on overall functional effect assessed by CDR at Weeks 8 and 12 post-dose | Weeks 8 and 12 post-dose | 
| K-IADL | * To compare the efficacy of 2 doses of PM012 Tablet and placebo based on activities of daily living assessed by K-IADL at Weeks 8 and 12 post-dose | Weeks 8 and 12 post-dose | 
| NPI | * To compare the efficacy of 2 doses of PM012 Tablet and placebo based on behavioral changes assessed by NPI at Weeks 8 and 12 post-dose | Weeks 8 and 12 post-dose | 
| K-MMSE | * To compare the efficacy of 2 doses of PM012 Tablet and placebo based on cognitive effect assessed by K-MMSE at Weeks 8 and 12 post-dose | Weeks 8 and 12 post-dose | 
| VAS | * To compare the efficacy of 2 doses of PM012 Tablet and placebo based on improvement on VAS assessed by Senile Dementia Pattern Identification Diagnosis System at Weeks 8 and 12 post-dose | at Weeks 8 and 12 post-dose | 
| AE | * To compare the safety based on treatment-emergent adverse events, laboratory tests (hematology/blood chemistry, urinalysis), physical examination, vital signs | while the subject is receiving the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease