Zydena on Cognitive Function of Alzheimer's Disease Patients

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

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.

Study Overview

• Status: Unknown
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Zydena (Udenafil) 50mg + Donepezil 5mg or 10mg; Drug: Placebo + Donepezil 5mg or 10mg; Drug: Zydena (Udenafil) 100mg + Donepezil 5mg or 10mg

• Study Type: Interventional
• Enrollment (Anticipated): 210
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Enda Go, Clinical Research Coordinator; Phone Number: 82-2-3410-2868; Email: ed.ko@samsung.com
• Study Contact Backup: Name: Duk L. Na, MD. PhD; Phone Number: 3599 82-2-3410-3599; Email: dukna@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samguns Medical Center
    • Contact: Enda Go, Clinical Research Coordinator; Phone Number: 82-2-3410-2868; Email: ed.ko@samsung.com
    • Principal Investigator: Duk L. Na, MD. PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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®)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zydena 50mg; Zydena (Udenafil) 50mg + Donepezil 5mg or 10mg	Drug: Zydena (Udenafil) 50mg + Donepezil 5mg or 10mg; Other Names: Zydena 50mg
Placebo Comparator: Placebo; Placebo + Donepezil 5mg or 10mg	Drug: Placebo + Donepezil 5mg or 10mg; Other Names: Placebo
Active Comparator: Zydena 100mg; Zydena (Udenafil) 100mg + Donepezil 5mg or 10mg	Drug: Zydena (Udenafil) 100mg + Donepezil 5mg or 10mg; Other Names: Zydena 100mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Dong-A Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: September 9, 2013
• First Submitted That Met QC Criteria: September 9, 2013
• First Posted (Estimate): September 12, 2013

Study Record Updates

• Last Update Posted (Estimate): September 12, 2013
• Last Update Submitted That Met QC Criteria: September 9, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Nootropic Agents; Phosphodiesterase 5 Inhibitors; Cholinesterase Inhibitors; Donepezil; Udenafil
• Other Study ID Numbers: 2012-03-065 (Other Identifier: Samsung Medical Center)