Efficacy, Safety and Tolerability of Tideglusib to Treat Mild-to-Moderate Alzheimer's Disease Patients

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the cognitive changes after administration of tideglusib versus placebo at two oral doses and two treatment regimes for 26 weeks in patients with mild to moderate Alzheimer's disease. After the 26 week core treatment period, the patients may continue in the study under blinded conditions for an optional extension period up to a maximum of 39 additional weeks (total study duration up to 65 weeks), until the last patient in the study has completed the 26 week of treatment.

Detailed Description
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This double-blind, placebo-controlled, randomized, parallel group study will be conducted at multiple centers in the European Union. Patients with mild to moderate Alzheimer's disease will undergo a screening period, and then they will be randomized to one of these four groups: tideglusib 1000 mg once daily (Q.D.), tideglusib 1000 mg every other day (Q.O.D.), tideglusib 500 mg Q.D., or matching placebo, for a 26-week, double-blind, placebo-controlled treatment period.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, 4-arm, 26 Week Parallel-Group Study to Evaluate Efficacy, Safety and Tolerability of 2 Oral Doses and 2 Regimes of Tideglusib vs Placebo in Mild-to-Moderate AD Patients

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: tideglusib
* Drug: tideglusib
* Drug: tideglusib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Men and women (of non-childbearing potential) with a diagnosis of probable Alzheimer's disease. Age of 50 to 85 years. MMSE score 14 to 26. Well-tolerated treatment with one of the approved Acetylcholinesterase-Inhibitors and/or Memantine in a stable dose Main Exclusion Criteria: Significant psychiatric on medical disease. 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 Chronic daily drug intake of excluded concomitant medications. Enrollment in another investigational drug study within 3 months before the baseline visit.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tideglusib 1000 mg Q.D.<br>Group dosed with 1000 mg once daily for 26 weeks/extension | Drug: tideglusib<br>* 1000 mg of tideglusib as a powder for oral suspension once daily in an overnight fasted state for 26 weeks/extension.<br>* Other names: NP031112;|
| Experimental: Tideglusib 1000 mg Q.O.D.<br>Group dosed with 1000 mg once every other day for 26 weeks/extension | Drug: tideglusib<br>* 1000 mg of tideglusib as a powder for oral suspension once every other day in an overnight fasted state for 26 weeks/extension<br>* Other names: NP031112;|
| Experimental: Tideglusib 500 mg Q.D.<br>Group dosed with 500 mg once daily for 26 weeks/extension | Drug: tideglusib<br>* 500 mg of tideglusib as a powder for oral suspension once daily in an overnight fasted state for 26 weeks/extension.<br>* Other names: NP031112;|
| Placebo Comparator: Placebo<br>Once daily administration for 26 weeks/extension | Drug: Placebo<br>* Powder for oral suspension administered once daily in an overnight fasted state for 26 weeks/extension.<br>* Other names: NP031112;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAS-Cog+ | The change 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+) | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs): Number of AEs and patients with an incidence rate of ≥ 5% AEs |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Alzheimer's Disease Cooperative Study Unit Activities of Daily Living (ADCS-ADL). |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Mini Mental State Examination (MMSE) |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Word Fluency test |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Neuropsychiatric Inventory (NPI) |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Geriatric Depression Scale (GDS) |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Clinical Global Impression of Change (CGIC) |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the European Quality of life Instrument (EQ-5D) |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Caregiver time (RUD Lite) |  | 26 weeks | 
| Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Questionnaire on urinary incontinence |  | 26 weeks | 
| Exploratory Endpoints (only in a subgroup of patients at predefined sites): Change from Baseline of the 3 active study medication groups will be compared with the placebo group in levels of τ, phospho-τ, and β-amyloid in CSF and change in MRI measures. |  | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tideglusib, Alzheimer, NP-12, NP031112, ARGO, Noscira