Alzheimer's Disease (mild to moderate) MedDRA version: 13.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: tideglusib
Product Code: NP031112-F06-037
Pharmaceutical Form: Powder for oral suspension
INN or Proposed INN: tideglusib
CAS Number: 865854-05-3
Current Sponsor code: NP031112-F06-037
O
Sponsors
Noscira S.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men and women (of non-childbearing potential) with a diagnosis of probable Alzheimer’s disease, according to the NINCDS-ADRDA clinical criteria of AD and DSM-IV criteria of dementia. 2. Age of 50 to 85 years (patients out of this range could be included after a previous assessment by the Investigator and approved by the sponsor). 3. Brain MRI study within 12 months before the Baseline visit supporting the clinical diagnosis (e.g. diffuse, symmetric, brain atrophy predominating in medial temporal regions) and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 2). 4. Mild to moderate stage of Alzheimer’s disease according to MMSE score 14 to 26. 5. Evidence of cognitive and/or functional decline in the past 6 months (in comparison with previous assessments) based either on a formal rating scale or a structured interview. 6. No relevant depression as indicated by score in Geriatric Depression Scale below or equal to 10. 7. Female patients must be either surgically sterilized or at least one year postmenopausal (confirmed by FSH >20, for women not surgically sterilized). Male patients must be willing to use barrier contraception (condom) during the study and for six months after the last treatment administration if their partners are women of child-bearing potential. 8. Good general health, hydration and nutrition status for participating in this clinical trial 9. Patients living at home or in long stay residential or care settings not requiring continuous and extensive nursing care; able to walk independently with or without a walking aid (e.g. cane or walker) 10. Ability to swallow a water suspension. 11. The patient and the caregiver are fluent in the language used for administration of the rating scales and cognitive tests and have sufficient visual, hearing, reading and writing skills to perform all the planned assessments. 12. Well-tolerated treatment with one of the approved Acetylcholinesterase-Inhibitors (Donepezil, Galantamine or Rivastigmine) and/or Memantine in a stable dose for at least 4 months prior to baseline evaluations. Any of these drugs must be anticipated not to be started or adjusted during the ongoing study. 13. A caregiver/nurse is available and is living in the same household or interacts with the patient at least 10 hours/week to assure the correct storage, preparation and administration of the study drug, as well as to provide information about patient’s physical and behavioral symptoms and changes. 14. Patients and caregivers must be able to understand and agree to comply with the prescribed dosage regimens and procedures, attend regularly scheduled visits and reliably communicate effectively with the investigator team. 15. Signed informed consent by patient (and/or legal representative if applicable) and caregiver prior to the initiation of any study-specific procedure. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range ;Inclusion criteria: 1. Men and women (of non-childbearing potential) with a diagnosis of probable Alzheimer’s disease, according to the NINCDS-ADRDA clinical criteria of AD and DSM-IV criteria of dementia. 2. Age of 50 to 85 years (patients out of this range could be included after a previous assessment by the Investigator and approved by the sponsor). 3. Brain MRI study within 12 months before the Baseline visit supporting the clinical diagnosis (e.g. diffuse, symmetric, brain atrophy predominating in medial temporal regions) and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 2). 4. Mild to moderate stage of Alzheimer’s disease according to MMSE score 14 to 26. 5. Evidence of cognitive and/or functional decline in the past 6 months (in comparison with previous assessments) based either on a formal rating scale or a structured interview. 6. No relevant depression as indicated by score in Geriatric Depression Scale below or equal to 10. 7. Female patients must be either surgically sterilized or at least one year postmenopausal (confirmed by FSH >20, for women not surgically sterilized). Male patients must be willing to use barrier contraception (condom) during the study and for six months after the last treatment administration if their partners are women of child-bearing potential. 8. Good general health, hydration and nutrition status for participating in this clinical trial 9. Patients living at home or in long stay residential or care settings not requiring continuous and extensive nursing care; able to walk independently with or without a walking aid (e.g. cane or walker) 10. Ability to swallow a water suspension. 11. The patient and the caregiver are fluent in the language used for administration of the rating scales and cognitive tests and have sufficient visual, hearing, reading and writing skills to perform all the planned assessments. 12. Well-tolerated treatment with one of the approved Acetylcholinesterase-Inhibitors (Donepezil, Galantamine or Rivastigmine) and/or Memantine in a stable dose for at least 4 months prior to baseline evaluations. Any of these drugs must be anticipated not to be started or adjusted during the ongoing study. 13. A caregiver/nurse is available and is living in the same household or interacts with the patient at least 10 hours/week to assure the correct storage, preparation and administration of the study drug, as well as to provide information about patient’s physical and behavioral symptoms and changes. 14. Patients and caregivers must be able to understand and agree to comply with the prescribed dosage regimens and procedures, attend regularly scheduled visits and reliably communicate effectively with the investigator team. 15. Signed informed consent by patient (and/or legal representative if applicable) and caregiver prior to the initiation of any study-specific procedure. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Hospitalization within 4 weeks prior to or during the screening period (apart from preplanned hospitalization for a condition, which did not deteriorate since 4 weeks prior to the screening period), or change of chronic concomitant medication (except vitamin or nutritional supplements) within 4 weeks prior to baseline. 2. Clinical, laboratory or neuroimaging findings consistent with: • other primary degenerative dementia, (dementia with Lewy bodies, Parkinson’s disease with dementia, fronto-temporal dementia, Huntington’s disease, Jacob- Creutzfeld Disease, Down’s syndrome, etc) • cerebrovascular disease as major, cortical, strategic (anterior thalamus, genu of internal capsule, or basal forebrain) infarction or more than 2 lacunar infarcts, or extensive white matter lesions scoring 3 in the Wahlund’s scale [Wahlund et al., 2001], or multi-infarct dementia. • other central nervous system lesions (hydrocephalus, severe head trauma, tumors, subdural hematomas or other relevant space occupying processes, etc.) • other relevant infectious, metabolic or systemic diseases affecting central nervous system (syphilis, juvenile onset diabetes mellitus, clinically significant vitamin B12,folate or thyroid deficiency, clinically significant serum electrolyte disturbances, etc.) 3. A current DSM-IV diagnosis of schizophrenia, bipolar disorder or active major depression. 4. Any chronic liver disease as indicated by out of range values of ALAT, ASAT or direct bilirubin, clinically relevant hepatic steatosis or other clinical manifestations of liver disease. 5. Clinical or historical evidence of active hepatitis or positive serology for hepatitis B or C. 6. History of hepatic drug intolerance or any significant drug allergy (such as Steven- Johnson syndrome, anaphylaxis). 7. Any clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as: • uncontrolled diabetes mellitus (HbA1c >8%) • renal insufficiency (serum creatinine >2mg/dl and creatinine clearance = 60 mL/min according to Cockgroft-Gault formula) • respiratory insufficiency • myocardial infarction, unstable angina within 3 months before screening • heart failure, cardiomyopathy • persistent bradycardia (heart beat 100/min) • episodes of unstable or uncontrolled blood pressure (systolic >160 or 100 or 450 msec for males and >470 msec for females using Fridericia’s formula: QTc = QT/cube root of RR). • active, peptic ulceration or gastrointestinal bleeding within 6 months • malignant tumors or metastases within 3 years except indolent prostate or skin malignancies (other than melanoma) 8. Chronic daily drug intake of: • drugs metabolized by the CYP3A4 with narrow therapeutic window: acenocumarol, warfarin and digitoxin • systemic anticholinergics with relevant action on central nervous system • tricyclics, MAO inhibitors or opioid analgesics • sedatives with the exception of sleep inducers of short action or Lorazepam max 1mg/day • neuroleptics except quetiapine (max 25 mg/day) or risperidone (max 1 mg/day) • ;Exclusion criteria: 1. Hospitalization within 4 weeks prior to or during the screening period (apart from preplanned hospitalization for a condition, which did not deteriorate since 4 weeks prior to the screening period), or change of chronic concomitant medication (except vitamin or nutritional supplements) within 4 weeks prior to baseline. 2. Clinical, laboratory or neuroimaging findings consistent with: • other primary degenerative dementia, (dementia with Lewy bodies, Parkinson’s disease with dementia, fronto-temporal dementia, Huntington’s disease, Jacob- Creutzfeld Disease, Down’s syndrome, etc) • cerebrovascular disease as major, cortical, strategic (anterior thalamus, genu of internal capsule, or basal forebrain) infarction or more than 2 lacunar infarcts, or extensive white matter lesions scoring 3 in the Wahlund’s scale [Wahlund et al., 2001], or multi-infarct dementia. • other central nervous system lesions (hydrocephalus, severe head trauma, tumors, subdural hematomas or other relevant space occupying processes, etc.) • other relevant infectious, metabolic or systemic diseases affecting central nervous system (syphilis, juvenile onset diabetes mellitus, clinically significant vitamin B12,folate or thyroid deficiency, clinically significant serum electrolyte disturbances, etc.) 3. A current DSM-IV diagnosis of schizophrenia, bipolar disorder or active major depression. 4. Any chronic liver disease as indicated by out of range values of ALAT, ASAT or direct bilirubin, clinically relevant hepatic steatosis or other clinical manifestations of liver disease. 5. Clinical or historical evidence of active hepatitis or positive serology for hepatitis B or C. 6. History of hepatic drug intolerance or any significant drug allergy (such as Steven- Johnson syndrome, anaphylaxis). 7. Any clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as: • uncontrolled diabetes mellitus (HbA1c >8%) • renal insufficiency (serum creatinine >2mg/dl and creatinine clearance = 60 mL/min according to Cockgroft-Gault formula) • respiratory insufficiency • myocardial infarction, unstable angina within 3 months before screening • heart failure, cardiomyopathy • persistent bradycardia (heart beat 100/min) • episodes of unstable or uncontrolled blood pressure (systolic >160 or 100 or 450 msec for males and >470 msec for females using Fridericia’s formula: QTc = QT/cube root of RR). • active, peptic ulceration or gastrointestinal bleeding within 6 months • malignant tumors or metastases within 3 years except indolent prostate or skin malignancies (other than melanoma) 8. Chronic daily drug intake of: • drugs metabolized by the CYP3A4 with narrow therapeutic window: acenocumarol, warfarin and digitoxin • systemic anticholinergics with relevant action on central nervous system • tricyclics, MAO inhibitors or opioid analgesics • sedatives with the exception of sleep inducers of short action or Lorazepam max 1mg/day • neuroleptics except quetiapine (max 25 mg/day) or risperidone (max 1 mg/day) •
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the cognitive changes after administration of tideglusib vs. placebo at two oral doses and 2 treatment regimes for 26 weeks in patients with mild to moderate Alzheimer’s disease;Secondary Objective: Key Secondary Objective: • To evaluate the safety and tolerability of two doses and two treatment regimes of tideglusib administered for 26 weeks in patients with mild-to-moderate Alzheimer’s disease. Other Secondary Objectives: • To evaluate other clinical changes in these patients after administration of tideglusib vs. placebo at 2 oral doses and 2 treatment regimes for 26 weeks: - patient daily functioning - behavior and depressive mood - overall clinical change - health related quality of life - caregiver time - urinary incontinence • To evaluate the safety and tolerability of tideglusib in patients administered over longer periods of time (more than 26 weeks; extension study).;Primary end point(s): Primary Efficacy Endpoint: The changes from Baseline of the 3 active study medication groups will be compared with the placebo group in: • Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog+);Main Objective: To evaluate the cognitive changes after administration of tideglusib vs. placebo at two oral doses and 2 treatment regimes for 26 weeks in patients with mild to moderate Alzheimer’s disease;Secondary Objective: Key Secondary Objective: • To evaluate the safety and tolerability of two doses and two treatment regimes of tideglusib administered for 26 weeks in patients with mild-to-moderate Alzheimer’s disease. Other Secondary Objectives: • To evaluate other clinical changes in these patients after administration of tideglusib vs. placebo at 2 oral doses and 2 treatment regimes for 26 weeks: - patient daily functioning - behavior and depressive mood - overall clinical change - health related quality of life - caregiver time - urinary incontinence • To evaluate t | — |
Countries
Finland, Germany, Spain, United Kingdom
Contacts
Public Contact; ;
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Outcome results
None listed