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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: tideglusib; Drug: tideglusib; Drug: tideglusib; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 306
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven and 4 additional cities, Belgium
• Finland
  • Turku and 3 additional cities, Finland
• France
  • Paris and 10 additional cities, France
• Germany
  • Freiburg and 5 additional cities, Germany
• Spain
  • Madrid and 7 additional cities, Spain
• United Kingdom
  • London and 11 additional cities, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tideglusib 1000 mg Q.D.; Group dosed with 1000 mg once daily for 26 weeks/extension	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: NP031112; NP-12; 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: NP031112; NP-12; 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: NP031112; NP-12
Experimental: Tideglusib 1000 mg Q.O.D.; Group dosed with 1000 mg once every other day for 26 weeks/extension	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: NP031112; NP-12; 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: NP031112; NP-12; 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: NP031112; NP-12
Experimental: Tideglusib 500 mg Q.D.; Group dosed with 500 mg once daily for 26 weeks/extension	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: NP031112; NP-12; 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: NP031112; NP-12; 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: NP031112; NP-12
Placebo Comparator: Placebo; Once daily administration for 26 weeks/extension	Drug: Placebo; Powder for oral suspension administered once daily in an overnight fasted state for 26 weeks/extension.; Other Names: NP031112; NP-12

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Noscira SA
• Collaborators: ICON Clinical Research
• Investigators: Study Director: Teodoro del Ser, PhD, Noscira SA

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: May 6, 2011
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Estimate): October 2, 2012
• Last Update Submitted That Met QC Criteria: October 1, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Alzheimer; tideglusib; NP-12; NP031112; ARGO; Noscira
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: NP031112-10B04