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

Sponsor

Noscira SA (Industry)

Overall Status

Completed

CT.gov ID

NCT01350362

Collaborator

ICON Clinical Research (Industry)

306

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

2.8

Patients Per Site Per Month

Study Details

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: tideglusib 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

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 :

Apr 1, 2011

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Oct 1, 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

ADAS-Cog+ [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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	City	Country
1	Leuven and 4 additional cities	Belgium
2	Turku and 3 additional cities	Finland
3	Paris and 10 additional cities	France
4	Freiburg and 5 additional cities	Germany
5	Madrid and 7 additional cities	Spain
6	London and 11 additional cities	United Kingdom