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

• Adverse events (AEs): Number of AEs and patients with an incidence rate of ≥ 5% AEs [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
• 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). [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Mini Mental State Examination (MMSE) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Word Fluency test [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Neuropsychiatric Inventory (NPI) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Geriatric Depression Scale (GDS) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• 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) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• 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) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Caregiver time (RUD Lite) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• Change from Baseline of the 3 active study medication groups will be compared with the placebo group in the Questionnaire on urinary incontinence [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
• 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. [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]

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.

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.

• Drug: tideglusib
  1000 mg of tideglusib as a powder for oral suspension once daily in an overnight fasted state for 26 weeks/extension.
  Other Names:

  • NP-12
  • NP031112
• Drug: tideglusib
  1000 mg of tideglusib as a powder for oral suspension once every other day in an overnight fasted state for 26 weeks/extension
  Other Names:

  • NP-12
  • NP031112
• Drug: tideglusib
  500 mg of tideglusib as a powder for oral suspension once daily in an overnight fasted state for 26 weeks/extension.
  Other Names:

  • NP-12
  • NP031112
• Drug: Placebo
  Powder for oral suspension administered once daily in an overnight fasted state for 26 weeks/extension.
  Other Names:

  • NP-12
  • NP031112

• Experimental: Tideglusib 1000 mg Q.D.
  Group dosed with 1000 mg once daily for 26 weeks/extension
  Intervention: Drug: tideglusib
• Experimental: Tideglusib 1000 mg Q.O.D.
  Group dosed with 1000 mg once every other day for 26 weeks/extension
  Intervention: Drug: tideglusib
• Experimental: Tideglusib 500 mg Q.D.
  Group dosed with 500 mg once daily for 26 weeks/extension
  Intervention: Drug: tideglusib
• Placebo Comparator: Placebo
  Once daily administration for 26 weeks/extension
  Intervention: Drug: Placebo

Main Inclusion Criteria:

1. Men and women (of non-childbearing potential) with a diagnosis of probable Alzheimer's disease.
2. Age of 50 to 85 years.
3. MMSE score 14 to 26.
4. Well-tolerated treatment with one of the approved Acetylcholinesterase-Inhibitors and/or Memantine in a stable dose

Main Exclusion Criteria:

1. Significant psychiatric on medical disease.
2. 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
3. Chronic daily drug intake of excluded concomitant medications.
4. Enrollment in another investigational drug study within 3 months before the baseline visit.