Mild to moderate Alzheimer's disease 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: LM11A-31-BHS
Product Code: LM11A-31-BHS
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LM11A-31-BHS
Current Sponsor code: LM11A-31-BHS
Other descriptive name: LM11A-31-BHS
Sponsors
Pharmatrophix Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women (non-childbearing potential) with a diagnosis of Alzheimer’s disease according to McKhann (2011) criteria 2. Age 50 - 85 years 3. MRI or CT assessment within six months before baseline, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3) 4. CSF AD specific biomarker profile; positive, defined as CSF Aß42 =65 years) yes F.1.3.1 Number of subjects for this age range 160
Exclusion criteria
Exclusion criteria: 1. Failure to perform screening or baseline examinations 2. Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period 3. Clinical, laboratory or neuro-imaging findings consistent with: • Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington’s disease, Creutzfeldt-Jakob Disease, Down's syndrome, etc.) • Other neurodegenerative condition (Parkinson’s disease, amyotrophic lateral sclerosis, etc.) • Cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions > one quarter of the total white matter) • Other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.) • Seizure disorder • Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.) 4. A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder 5. Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as: • Chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, Gamma GT, alkaline phosphatase > 2.5 ULN) • Respiratory insufficiency • Renal insufficiency (serum creatinine >2mg/dl) or creatinine clearance = 30 mL/min according to Cockcroft-Gault formula. In case of creatinine clearance =30mL/min, an alternative verification of the renal function must be completed using Cystatin C analysis. In case of normal level of Cystatin C, the patient can be included • Heart disease (myocardial infarction, unstable angina, heart failure, Cardiomyopathy within six months before screening) • Bradycardia (heart beat 95/min.) • Hypertension (>180/95) or hypotension (450 and females >470 msec) •Uncontrolled diabetes defined by HbA1c >8.5 • Malignancies within the last five years except skin malignancies (other than melanoma) or indolent prostate cancer • Metastases 6. Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.) 7. Women who are fertile and of childbearing potential 8. Chronic daily drug intake of = 14 days or expected for = 14 days: • Benzodiazepines, neuroleptics or major sedatives • Antiepileptics • Centrally active anti-hypertensive drugs (clonidine, l-methyl DOPA, guanidine, guanfacine, etc.) • Opioid containing analgesics 9. Nootropic drugs (except Ginkgo Biloba) 10. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV significantly above normal value at screening 11. Suspected or known allergy to any components of the study treatments 12. Enrollment in another investigational study or intake of investigational drug within the previous three months 13. Any condition,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of 200mg bid and 400mg bid doses of LM11A-31-BHS (free base) administered for a period of 26 weeks in comparison to placebo. Safety will be assessed through adverse event reporting, clinical laboratory, ECG and a standard range of patient physical evaluations including a suicide severity rating scale (C-SSRS). ;Secondary Objective: Exploratory investigation of relevant biomarkers for AD and drug mechanism including regional brain glucose metabolism (18F-FDG-PET) and CSF measures. The assessment of exploratory clinical endpoints including a composite of the specific cognitive tests performed (the NTB composite standardized Z score). The investigation of the pharmacokinetics of 200mg bid and 400mg bid doses of LM11A-31-BHS (free base) administered for a period of 26 weeks. PK parameters for LM11A-31 and its aminoethyl morpholine metabolite will be estimated using noncompartmental analysis (NCA). ;Primary end point(s): All safety evaluations will be summarized as interval or categorical summaries as appropriate. The overall incidence of adverse events, together with the top three most frequently reported adverse events, will be analyzed using a binary logistic model to demonstrate differences between the treatment groups and placebo. The end points include alls Adverse events (AEs), Serious adverse events (SAEs), Clinical Diagnostics, Vital signs (blood pressure, heart rate, respiratory rate, body temperature), ECG, Laboratory assessment (hematology, biochemistry, coagulation, serology and urinalysis), Columbia-Suicide Severity Rating Scale (C-SSRS), MRI scans (analyzed by a central reader);Timepoint(s) of evaluation of this end point: Changes between baseline and end of study visit (26 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Changes between baseline and end of study visit (26 weeks);Secondary end point(s): All exploratory efficacy variables will be analyzed at the endpoint (Final visit). The analyses will involve the change from baseline in the NTB composite summary Z score calculated after 6 months (26 weeks) of treatment. This will involve an Analysis Of Covariance Variance (ANCOVA) model incorporating the baseline score and country as covariates. Additional analyses will involve evaluation of the time course of treatment response over the treatment period, using a repeated measures mixed model Analysis of Covariance (ANCOVA) for evaluation. 18F-Pet Scan variables will be analyzed in a descriptive and exploratory manner. Categorical endpoints will be analyzed using a Cochran Mantel-Haenszel (CMH-row mean scores difference), chi-squared test or Logistic regression models (as appropriate). Exploratory/ Candidate Efficacy variables • CSF-Biomarkers (tau, ptau, Aß40, Aß42, AchE activity) • Regional brain glucose metabolism (18FDG-PET) • NTB: o Digit Span Test o Category Fluency Test o COWAT o Digit Symbol Substitution Test (DSST) • ADAS-cog 13 items • SPATIAL ORIENTATION AND LEARNING (Amunet) • Geriatric Depression Scale (GDS) • Clinical Global Impression Scale – Severity/Improvement (CGI-I/CGI-S) | — |
Countries
Austria, Czech Republic, Germany, Spain, Sweden
Contacts
Public ContactCRO
NeuroScios GmbH
Outcome results
None listed