Study to Evaluate the Efficacy and Safety of KDS2010 in Patients With Alzheimer's Disease With Mild Cognitive Impairment and Mild Dementia Due to Alzheimer's Disease

Exclusion Criteria

• •Cognitive impairment or dementia due to causes other than Alzheimer's disease
• •* Vascular dementia, central nervous system infections (e.g., HIV, syphilis, etc.), head trauma, Creutzfeldt-Jakob disease, Pick's disease, Huntington's disease, Parkinson's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor, thyroid disorders, parathyroid disorders, Vitamin B12 deficiency, folic acid deficiency, other metabolic and nutritional deficiencies, etc.
• •* Alcohol or drug abuse, dependence
• •Subjects with cognitive impairment due to hypothyroidism, nutritional deficiencies, Vitamin B12 or folic acid deficiency as assessed during screening
• •Subjects confirmed during screening to have had the following medical history:
• •* Malignant tumors within five years prior to screening except for basal cell carcinoma, cutaneous squamous cell carcinoma, thyroid cancer, or carcinoma in situ that has not recurred in over three years and is considered successfully treated by the investigator
• •* History of alcohol or drug abuse within two years prior to screening
• •* Loss of consciousness of unknown cause, or seizure within the past 52 weeks before screening
• •* Unstable and clinically significant cardiovascular diseases despite appropriate treatment (acute coronary syndrome (ACS), tachycardia, clinically significant arrhythmias, cardiomyopathy, angina of at least CSS III, heart failure of NYHA II-IV, or clinically significant valvular heart disease) within 24 weeks before baseline
• •* Severe or active infectious diseases requiring antibiotics or antivirals within four weeks before baseline
• •* A history of stroke involving a major vascular area, transient ischemic attack (TIA), epilepsy, or severe head trauma with loss of consciousness
• •* Hypersensitivity or allergy to any components of the investigational product
• •Subjects confirmed during screening to have had the following accompanying disease:
• •* Clinically significant neurological diseases or serious pathological findings affecting cognitive function as confirmed by brain imaging studies within 52 weeks prior to screening, including multiple sclerosis, normal pressure hydrocephalus, brain tumor (however, exceptions are allowed for lesions diagnosed as benign and with a maximum diameter of less than 1 cm), spinal cord infarction, major hemorrhage (defined as having a diameter \> 1 cm in MRI) or subdural hemorrhage, cerebral vascular malformation, communicating hydrocephalus, inflammatory demyelinating diseases, etc.
• •* Uncontrolled hypertension despite appropriate treatment at screening or baseline (SBP ≥160 mmHg or DBP ≥100 mmHg)
• •* Dizziness or fainting when standing due to orthostatic hypotension that may affect the evaluation according to the judgment of the investigator
• •* Uncontrolled diabetes (HbA1c \> 9%) during screening, despite appropriate treatment
• •* Bleeding disorders (Platelet \<50,000/mm³) during screening, despite appropriate treatment
• •* Patients with severe hepatic impairment (Child-pugh class C) at screening
• •* Following laboratory test values at screening:
• •* AST or ALT \> 2.5 x ULN
• •* total bilirubin \> 1.5 x ULN (however, in case of Gilbert syndrome, \> 3.0 mg/dL)
• •* MDRD eGFR \< 30 mL/min/1.73 m²
• •* QTcF interval \>450 msecs (12-lead ECG) during screening
• •* Gastrointestinal diseases that may affect oral administration or absorption (celiac disease, Crohn's disease, intestinal resection, etc.)
• •* Gastrointestinal diseases, including gastric and duodenal ulcers, that may affect the safety evaluation according to the judgment of the investigator
• •* Psychiatric diagnosis or symptoms that may interfere with the study (uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder, etc.), as assessed by the investigator
• •* Positive responses to items 4 or 5 on the Columbia University Suicide Severity Rating Scale (C-SSRS) during screening
• •* Other conditions deemed by the investigator to potentially affect the outcome of the study
• •Subjects who have undergone or require treatment with the following:
• •* AD disease-modifying agents (aducanumab, lecanemab, donanemab, gantenerumab, solanezumab, blarcamesine, simufilam, tricaprilin, valiltramiprosate, etc.) within 12 weeks before screening
• •* Medications that may improve cognitive abilities or affect AD treatment (AChEIs, donepezil, galantamine, rivastigmine, tacrine, memantine, etc.) within 12 weeks before screening, except if the subject has been on a stable dose for at least 12 weeks before baseline and maintains the same composition/dosage/method of administration during the study period
• •* CNS-active drugs or those affecting cognitive function antidepressants other than serotonergic drugs \[e.g., bupropion\], sedatives \[e.g., carbamazepine\], dopamine antagonists \[e.g., antipsychotics, metoclopramide\], amfepramone, mazindol) within 12 weeks before screening
• •* Central anticholinergics and sedating H1-antihistamines within 12 weeks before screening.
• •However, exceptions are allowed for one-time use of the drugs, such as second-generation H1 antihistamines (e.g., cetirizine, levocetirizine, etc.) or peripheral anticholinergics with no central action (e.g., trospium for treating overactive bladder). But the use is prohibited for at least 3 days from the date of cognitive function evaluation.
• •Other investigational products or clinical trial devices within four weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
• •Monoamine oxidase inhibitors (MAOIs) and linezolid within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
• •Opioids (pethidine, tramadol, tapentadol, etc.) within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
• •Cyclobenzaprine and St. John's wort within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
• •The following serotonergic drugs within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out),
• •* selective serotonin (5HT1) agonists
• •* lithium
• •* lamotrigine
• •* ritonavir
• •* dapoxetine
• •* Selective serotonin reuptake inhibitors (SSRIs)
• •* dapoxetine
• •* Serotonin-norepinephrine reuptake inhibitors (SNRIs)
• •* Tricyclic or tetracyclic antidepressants
• •* triazolopyridine antidepressant However, amitriptyline ≤ 50 mg/day, trazodone ≤ 100 mg/day, citalopram ≤ 20 mg/day, and sertraline ≤ 100 mg/day are allowed without washout.
• •Use of sympathomimetics (ephedrine, methylphenidate, amphetamine, methamphetamine, lisdexamfetamine, etc.) during the screening period
• •Use of Dextromethorphan during the screening period
• •Use of CYP3A4 strong inducer, CYP3A4 strong inhibitor, CYP2D6 strong inducer, and CYP2D6 strong inhibitor during the screening period
• •* Inability to undergo MRI or PET scans
• •* Pregnant or breastfeeding women
• •* Fertile women or men who are unwilling to use effective contraception\* from the date of written consent until 12 weeks after the last administration of the investigational product
• •\*Effective contraception is defined as follows, and at least one method should be used:
• •* Hormonal contraception (oral, injectable, implantable, etc.)
• •* Intrauterine device (IUD) or system (IUS)
• •* Sterilization or surgical procedures (vasectomy, bilateral tubal ligation/surgery, hysterectomy)
• •* Dual contraception methods: Simultaneous use of barrier methods (male condoms) with the methods listed above
• •* Absolute abstinence: Total abstinence from sexual intercourse is recognized if the investigator deems the subject's age, occupation, lifestyle, or sexual orientation assures contraception. However, periodic abstinence (calendar method, mucus method, and symptothermal method), withdrawal, and coitus interruptus are not recognized as effective contraception methods.
• •* Other conditions deemed by the investigator to be unsuitable for participation in the study