Zydena on Cognitive Function of Alzheimer's Disease Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Zydena (Udenafil) has positive effect on cognitive function in patients with Alzheimer's disease. This study is a randomized, double blind, placebo-controlled multicenter study.

Official Title
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Efficacy of Zydena (Udenafil) on Cognitive Function of Alzheimer's Disease Patients: A Randomized, Double Blind, Placebo-controlled Multicenter Study

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Zydena (Udenafil) 50mg + Donepezil 5mg or 10mg
* Drug: Placebo + Donepezil 5mg or 10mg
* Drug: Zydena (Udenafil) 100mg + Donepezil 5mg or 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent; Male or female subjects 50 to 90 years of age; Diagnosis of probable Alzheimer's disease according to National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria; A Mini-Mental State Examination (MMSE) score of ≥10 and ≤26; Global Clinical Dementia Rating ≥ 0.5; Mild to moderate (not severe) white matter hyperintensities on brain MRI performed within three years from screening; Good enough hearing and visual function to complete neuropsychological tests Caregivers living with patients or spending 10 or more hours a week with patients; Stable dose of donepezil (5mg to 10mg) for at least 60 days; If patients have been on memantine, it should be washed out for at least 60 days; Medications including anxiolytics, antipsychotics, and hypnotics may be taken if the dose has been stable for at least two weeks Exclusion Criteria: History of stroke within 6 months; Previous diagnosis of severe (more than 80%) intracranial artery stenosis; History of heart failure, ischemic heart disease (myocardial infarction, unstable angina, and stable angina), hypertrophic cardiomyopathy, and life-threatening arrhythmia; Previous history of coronary artery bypass graft surgery; Severe symptom of orthostatic hypotension (orthostatic syncope or presyncope), especially when patients take alpha-adrenergic blocker (Alfuzosin, Doxazosin, Naftopidil, Tamsulosin, Terazosin, Arotinolol, Carvedilol, Labetalol, Trazodone, typical and atypical antipsychotics); Uncontrolled diabetes mellitus; Proliferative diabetic retinopathy; Severe hypotension (blood pressure less than 90/50mmHg) or severe hypertension (blood pressure more than 170/100mmHg); Hepatic dysfunction (AST or ALT more than three times of upper normal limit) or renal dysfunction (serum creatinine more than 2.5mg/dL); Retinitis pigmentosa; Previous history of active peptic ulceration within one year before screening; Hematodyscrasia susceptible to priapism including sickle cell anemia, multiple myeloma, leukemia, and various bleeding disorders; History of drug abuse; Medication including nitrates/nitric oxide donor (ex: nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, amyl nitrate/nitrite, and Sodium nitroprusside), androgen (ex: testosterone), anti-androgen, and anticoagulants; Current cancer chemotherapy; Usage of PDE5i (Zydena, Viagra®, Levitra®, or Cialis®) within two weeks before study start; History of hypersensitive reaction to PDE5i (Zydena, Viagra®, Levitra®, or Cialis®)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 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 |
| --- | --- |
| Active Comparator: Zydena 50mg<br>Zydena (Udenafil) 50mg + Donepezil 5mg or 10mg | Drug: Zydena (Udenafil) 50mg + Donepezil 5mg or 10mg<br> <br> * Other names: Zydena 50mg;|
| Placebo Comparator: Placebo<br>Placebo + Donepezil 5mg or 10mg | Drug: Placebo + Donepezil 5mg or 10mg<br> <br> * Other names: Placebo;|
| Active Comparator: Zydena 100mg<br>Zydena (Udenafil) 100mg + Donepezil 5mg or 10mg | Drug: Zydena (Udenafil) 100mg + Donepezil 5mg or 10mg<br> <br> * Other names: Zydena 100mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive function | measured by ADAS-cog | from baseline to Week 12 and Week 24 after the administration of the medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive function | Measured by MMSE, Clinical Dementia Rating Sum of Boxes, ADCS-ADL, COWAT, Digit Symbol Coding, Trail Making Test-E | from baseline to Week 12 and Week 24 | 
| Change in behavioral symptoms | Measured by Neuropsychiatric Inventory | from baseline to Week 12 and Week 24 | 
| Change in brain function | Measured by FDG-PET | from baseline to Week 12 and Week 24 |