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
Overview
- Phase
- Phase 2
- Intervention
- PM012 Placebo
- Conditions
- Mild Alzheimer Disease
- Sponsor
- Mediforum Ltd., Co.
- Enrollment
- 312
- Locations
- 1
- Primary Endpoint
- ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female patients aged ≥ 50 and ≤ 85 years.
- •Patients clinically diagnosed as probable Alzheimer's disease based on DSM-IV and NINCDS-ADRDA criteria.
- •Patients between MMSE score of 20\~26 at screening visit.
- •Patients with Global CDR score of 0.5 or 1 at the screening visit.
- •Patients administered with donepezil 5㎎ stably for over 3 months or who have never been administered donepezil.
- •Patients who can perform cognitive or other necessary tests.
- •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).
- •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.
- •Patients who have signed the informed consent on his/her own will
Exclusion Criteria
- •Patients with hypersensitivity to the investigational product or components contained in the investigational product.
- •Patients with hypersensitivity to piperidine derivatives.
- •Patients with possible, probable or definite vascular dementia according to the NINDS-AIREN criteria.
- •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.
- •Patients who are illiterate.
- •Patients with severe hearing or visual disabilities so that efficacy assessment is impossible.
- •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.
- •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).
- •Patients with genetic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
- •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.
Arms & Interventions
Aricept 5 mg
Aricept 5 mg + Placebo of PM012 eight tablets, daily during 12 weeks (oral)
Intervention: PM012 Placebo
Aricept 5 mg
Aricept 5 mg + Placebo of PM012 eight tablets, daily during 12 weeks (oral)
Intervention: Donepezil
PM012 2,600 mg
PM012 2,600 mg + Placebo of PM012 four tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: PM012
PM012 2,600 mg
PM012 2,600 mg + Placebo of PM012 four tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: PM012 Placebo
PM012 2,600 mg
PM012 2,600 mg + Placebo of PM012 four tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: Donepezil placebo
PM012 3,900 mg
PM012 3,900 mg + Placebo of PM012 two tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: PM012
PM012 3,900 mg
PM012 3,900 mg + Placebo of PM012 two tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: PM012 Placebo
PM012 3,900 mg
PM012 3,900 mg + Placebo of PM012 two tablets +Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: Donepezil placebo
PM012 5,200 mg
PM012 5,200 mg + Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: PM012
PM012 5,200 mg
PM012 5,200 mg + Placebo of Aricept one tablet, daily during 12 weeks (oral)
Intervention: Donepezil placebo
Outcomes
Primary Outcomes
ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)
Time Frame: At 12 weeks post-dose
* 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)
Time Frame: At 12 weeks post-dose
* 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 Outcomes
- ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale)(At 8 weeks post-dose)
- ADCS-MCI-ADLI (Alzheimer's Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living Inventory)(At 8 weeks post-dose)
- CDR (Clinical Dementia Rating)(At 8 weeks and 12 weeks post-dose)
- MMSE (Mini Mental State Examination)(At 8 weeks and 12 weeks post-dose)
- NPI (Neuropsychiatric Inventory)(At 8 weeks and 12 weeks post-dose)
- Number of participants with adverse events, with abnormal physical exam findings and abnormal laboratory tests results.(At 12 weeks post-dose)