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

• ClinicalTrials.gov Identifier: NCT01350362
• Recruitment Status: Completed
• First Posted: May 9, 2011
• Last Update Posted: October 2, 2012
• Sponsor: Noscira SA
• Collaborator: ICON Clinical Research
• Information provided by (Responsible Party): Noscira SA

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: tideglusib; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 306 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2011
• Actual Primary Completion Date: July 2012
• Actual Study Completion Date: October 2012

Arms and Interventions

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: NP-12; NP031112
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 every other day in an overnight fasted state for 26 weeks/extension; Other Names: NP-12; NP031112
Experimental: Tideglusib 500 mg Q.D.; Group dosed with 500 mg once daily for 26 weeks/extension	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
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: NP-12; NP031112

Outcome Measures

Primary Outcome Measures :

1. ADAS-Cog+ [ Time Frame: 26 weeks ]
   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+)

Secondary Outcome Measures :

1. Adverse events (AEs): Number of AEs and patients with an incidence rate of ≥ 5% AEs [ Time Frame: 26 weeks ]
2. 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 ]
3. 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 ]
4. 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 ]
5. 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 ]
6. 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 ]
7. 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 ]
8. 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 ]
9. 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 ]
10. 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 ]
11. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

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

Sponsors and Collaborators

Noscira SA

ICON Clinical Research

Investigators

• Study Director: Teodoro del Ser, PhD; Noscira SA

More Information

• Responsible Party: Noscira SA
• ClinicalTrials.gov Identifier: NCT01350362
• Other Study ID Numbers: NP031112-10B04
• First Posted: May 9, 2011
• Last Update Posted: October 2, 2012
• Last Verified: October 2012

Keywords provided by Noscira SA:

tideglusib; Alzheimer; NP-12; NP031112; ARGO; Noscira

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders