Sufficient clinical and paraclinical information for the diagnosis of Alzheimer’s Disease (AD) according to the international diagnosis criteria from McKhann G. M. et al. 2011 MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852 MedDRA version: 20.0 Level: LLT Classification code 10066571 Term: Progression of Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: NanoLithium® NP03
Pharmaceutical Form: Oral emulsion
Pharmaceutical form of the placebo: Oral emulsion
Route of administration of the placebo: Buccal use
Sponsors
MEDESIS PHARMA SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1) Male and female patients between 50 and 87 years of age; I2) Sufficient clinical and paraclinical information for the diagnosis of AD according to the international diagnosis criteria from McKhann G. M. et al. 2011; I3) NPI scale>2; I4) Patients with moderate-to-severe AD with a MMSE score from 10 and 22 included; I5) Symptomatic treatments of AD (acetylcholinesterase inhibitors and Memantine) and psychotics drugs (anxiolytics, thymic, neuroleptics) are allowed but need to be maintained during at least 4 weeks before inclusion and over the follow-up; I6) Female patient of childbearing potential must be willing to use an efficient birth control method during the study I7) Male patient must be willing to use male contraception (condom) during the study I8) Patients who have signed the informed consent form; I9) Patients affiliated to French social security. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: E1) Patients with genetic forms of AD (known genetic mutation); E2) Patients with major physical or neurosensory problems likely to interfere with the tests, contraindication, or refusal to perform functional brain imaging examinations; E3) Pathologies involving short term vital prognosis (progressive cancer, unstable heart failure, severe liver, kidney, or respiratory diseases); E4) Primary chronic psychosis or psychotic episodes not associated with the AD pathology; E5) Absence of caregivers to complete psychological and behavioral scales and/or questionnaires; E6) Patients with illiteracy and inability to perform psychological and behavioral evaluations; E7) Pregnancy or breast-feeding; E8) Addiction to alcohol or drugs; E9) Epilepsy or others neurodegenerative disorders; E10) Vitamin B12 or folic acid deficiency without supplementation; E11) Patients participating in another drug trial; E12) Thyroid disorders non treated; E13) Patients living in institution; E14) Patients deprived of liberty by law or administrative decision; E15) Major protected by law.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective (at 12 weeks): To evaluate the clinical efficacy of NanoLithium® NP03 versus placebo, on the progression of the behavioral and psychological symptoms of dementia (BPSD) between baseline and after 12 weeks of treatment in patients with moderate-to-severe AD. ;Secondary Objective: Secondary objectives (at 12 weeks, after the double-blind phase and at 48 weeks, after the open label 36-week phase): - To assess the clinical safety of NanoLithium® NP03 during 48 weeks in patients with AD from moderate-to-severe AD. - To evaluate the efficacy of NanoLithium® NP03 on: - the progression of the cognitive performances, - the progression of the BPSD, - the progression of the cortical hypometabolism in parieto-temporal regions. - To determine the potential disease-modifying effect of the NanoLithium® NP03 on the progression of AD pathophysiological biological peripheral biomarkers (amyloid, neurofilaments, Tau biomarkers, BNDF in plasma) and non-specific biomarkers (inflammation cytokines measured with cytokines assays). - To assess the effect of NanoLithium® NP03 on the progression of sleep/wake cycles. - To assess treatment compliance.;Primary end point(s): The primary endpoint will be the change from baseline to end of double-blind period (W12) of the NPI score in the NanoLithium® NP03 arm and in the placebo arm. ;Timepoint(s) of evaluation of this end point: NPI score | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary safety endpoints will be: - The number and types of adverse effects during the study and causal role of the study treatment - To assess the safety of the NanoLithium® NP03 after 48 weeks of treatment on common biological tests, clinical and neurological assessments Secondary efficacy endpoints will be assessed after 12 weeks of treatment (end of the double-blind period), and after 48 weeks of treatment (end of open-label period). The following endpoints will be used: - Behavioral and psychosocial troubles - Cognitive performances - Cerebral metabolic rate for glucose measured by the PET-FDG - Pathophysiological peripheral biomarkers (amyloid biomarkers, neurofilaments, Tau protein, BDNF) and non-specific biomarkers - Actigraphy-sleep/wake measures (sleep duration, sleep efficacy, daytime activity) and score of sleep/wake questionnaires - Drug treatment compliance will be assessed by the number of buccal deposits;Timepoint(s) of evaluation of this end point: - To assess the safety of the NanoLithium® NP03 after 48 weeks of treatment on common biological tests, clinical and neurological assessments: o Associated pathologies o Clinical laboratory evaluation: biochemistry, hematology, lithium blood levels o Vital signs: hear rate, diastolic blood pressure, systolic blood pressure o ECG o General clinical examination: weight, height, Body Mass Index (BMI) o Neurological clinical examination: cognitive signs, focal neurological signs, motricity - Behavioral and psychosocial troubles: o NPI-NH score o BDI score o Apathic score - Cognitive performances o MMSE score o Isaacs Set Test score o Trail Making Test A and B score o ADAS-Cog score o CDR score o IADL score | — |
Countries
France
Contacts
Public ContactChief Executive Officer
MEDESIS Pharma SA
Outcome results
None listed