Efficacy and Safety of DMB-I (INN: Latrepirdine) in Patients With Alzheimer Type Dementia

This is a multicenter randomized double-blind placebo-controlled two-stage study that is to assess efficacy and safety of DMB-I (INN: Latrepirdine) in patients with Alzheimer type dementia.

The study is planned to be conducted in approximately 15 clinical sites of the Russian Federation.

At Stage 1 (comparative stage, 26 weeks), the study will examine three treatment groups. Patients in Group 1 and Group 2 will receive Akatinol Memantine® in addition to the study therapy (DMB-I or Placebo). Patients in Group 3 will receive DMB-I alone. The study is double-blind for DMB-I and Placebo; Akatinol Memantine® will not be blinded.

Patients meeting all the eligibility criteria will be randomized into one of three treatment groups:

• DMB-I, 10 mg, 2 tablets 3 times daily + Akatinol Memantine®, 20 mg once daily - 175 patients (Group 1: DMB-I + Memantine).
• Placebo, 2 tablets 3 times daily + Akatinol Memantine®, 20 mg once daily - 175 patients (Group 2: Placebo + Memantine).
• DMB-I, 10 mg, 2 tablets 3 times daily - 100 patients (Group 3: DMB-I). Following completion of Stage 1, patients will continue participating in the open-label stage of the study (Stage 2) for additional 26 weeks to evaluate the long-term efficacy and safety of DMB-I. During this stage, patients in Group 1 (DMB-I + Memantine) will continue their study therapy unchanged. Patients in Group 2 (Placebo + Memantine) will discontinue Placebo and begin therapy with DMB-I (while continuing to take Akatinol Memantine®). Patients in Group 3 (DMB-I monotherapy) will also continue their therapy unchanged.

The total study duration for each patient is approximately 56 weeks broken down as follows:

Screening period: up to 2 weeks, Treatment period (Stage 1): 26 weeks, Treatment period (Stage 2): 26 weeks, Follow-up period: 2 weeks.

Inclusion criteria

• Inclusion Criteria (Group 1 and Group 2):

• Informed consent to participate in the study.
• Patients of any gender aged 60 to 90 years inclusive.
• Patients diagnosed with mild to moderate Alzheimer type dementia according to the NINCDS-ADRDA criteria, receiving basic treatment with memantine at a daily dose of 20 mg for at least 2 months.
• The MMSE score is in the range of 10-23 inclusive.
• The ADAS-Cog score is in the range of 20-54 inclusive.
• No signs of dementia of vascular origin according to CT/MRI data. Repeated Acute Cerebrovascular Accidents (focal infarctions) in brain areas that are critical for cognitive functions and behavior are the mandatory neuroimaging signs of vascular dementia.
• The Modified Hachinski Ischemic Scale (HIS) score is < 7.
• The presence of a caregiver who is in contact with the patient a significant part of the time, agrees to accompany the patient to all visits, monitor the intake of the study drug and fill out the patient's diary.
• An ability to comply with all Protocol requirements.
• Inclusion Criteria (Group 3):

• Informed consent to participate in the study.
• Patients of any gender aged 60 to 90 years inclusive.
• Patients diagnosed with mild to moderate Alzheimer type dementia according to the NINCDS-ADRDA criteria, who are not receiving dementia-contolling medications (memantine, donepezil, rivastigmine, or galantamine) at screening or for the last two (or more) months prior to screening; however, taking such medications for more than two months prior to screening does not limit a patient's participation in the study.
• The MMSE score is in the range of 10-23 inclusive.
• The ADAS-Cog score is in the range of 20-54 inclusive.
• No signs of dementia of vascular origin according to CT/MRI data. Repeated Acute Cerebrovascular Accidents (focal infarctions) in brain areas that are critical for cognitive functions and behavior are the mandatory neuroimaging signs of vascular dementia.
• The Modified Hachinski Ischemic Scale (HIS) score is < 7.
• The presence of a caregiver who is in contact with the patient a significant part of the time, agrees to accompany the patient to all visits, monitor the intake of the study drug and fill out the patient's diary.
• An ability to comply with all Protocol requirements.

Exclusion criteria

• Patients diagnosed with other diseases that cause dementia (severe hypothyroidism, anemia, brain tumor, neuroinfections, etc.) at screening.
• History of other neurodegenerative diseases of the brain, Parkinson's disease, multiple sclerosis, demyelinating diseases of the nervous system, hereditary degenerative diseases of the central nervous system, abnormalities of the nervous system, uncontrolled epilepsy, hallucinations, other neurological disorders seriously affecting motor or cognitive function, in the opinion of the investigator.
• History of intolerance to any of the components of the study drug.
• History of stroke.
• Active oncological process.
• The need for surgeries on the vessels of the neck or brain, including endovascular interventions, during the study.
• Signs of significant uncontrolled concomitant disease that, in the opinion of the Investigator, could prevent the patient from participating in the study, including:

• Respiratory system disorders;
• Cardiovascular system disorders;
• Severe renal impairment (glomerular filtration rate <30ml/min);
• Severe liver dysfunction (ALT, AST > 2 times the upper limit of normal);
• Endocrine system disorders;
• Gastrointestinal disorders.
• Systemic autoimmune diseases or vascular collagenoses requiring previous or current treatment with systemic drugs.
• Myocardial infarction within 12 months prior to screening.
• Known systemic infection (viral hepatitis, HIV, tuberculosis, syphilis).
• Life expectancy less than a year after randomization.
• Use of drugs that negatively affect cognitive function (tricyclic antidepressants, benzodiazepines, antipsychotics, hypnotics, etc.), as well as drugs of prohibited therapy (including Cerebrolysin, preparations of ginkgo biloba extract, any other drugs with nootropic, antioxidant, metabolic effects, as well as drugs used to treat dementia) within 1 month prior to screening.
• Moderate to severe depression (Hamilton scale score of 18 or more).
• Smoking.
• Episodes of alcohol or drug abuse within the last 6 months.
• Inability to comply with study procedures even with the assistance, in the opinion of the investigator.
• Participation in another clinical trial within the last 6 months.
• Episodes of other serious or unstable psychiatric conditions that make the patient unsuitable for participation in a clinical study, alter the validity of obtaining an informed consent, or may affect the patient's ability to participate in the trial.