Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's Disease

NCT00708552 | Completed Phase 2 Results

• 1 other identifier: AZ3110865
• Study Type: interventional
• Target: 576
• Locations: 11 countries
• Sites: 72

Brief Summary

The study is designed to investigate the efficacy, safety and tolerability of SB-742457 versus placebo in subjects with mild-to-moderate Alzheimer's disease. SB-742457 is an experimental treatment which increases the levels of certain chemicals in the brain that are often decreased in patients with Alzheimer's disease.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease; Cognition; SB-742457

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24

  ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a five point scale. The ADAS-Cog total score is the sum of the calculated scores for Questions 1 (Word recall task), 2 (Naming objects and fingers), and 7 (Word recognition task) and the scores recorded on the CRF for Questions 3 to 6 (Commands, Constructional praxis, Ideational praxis, Orientation) and 8 to 11 (Remembering test instructions, Spoken language ability, Word finding difficulty in spontaneous speech, Comprehension). The total score ranges from 0-70 with higher scores indicating greater dysfunction while lower indicates better cognitive function. Baseline was defined as the value at Week 0. Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

  Baseline (Week 0) and Week 24

• Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24

  The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse).

  Week 24

Secondary Outcomes (35)

• Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24

  Baseline (Week 0) and Week 24

• Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline Mini Mental State Examination [MMSE] Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24

  Baseline (Week 0) and Week 24

• Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline [MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24

  Baseline (Week 0) and Week 24

• Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 24

  Baseline (Week 0) and Week 24

• Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 24

  Baseline (Week 0) and Week 24

Study Arms (4)

SB-742457 - 15mg

EXPERIMENTAL

SB-742457 - 15mg

Drug: SB-742457

Placebo

PLACEBO COMPARATOR

Drug: Placebo

SB-742457 - 35mg

EXPERIMENTAL

SB-742457 - 35mg

Drug: SB-742457

Donepezil

ACTIVE COMPARATOR

Drug: Donepezil

Interventions

SB-742457 DRUG

investigational drug

SB-742457 - 15mg; SB-742457 - 35mg

Donepezil DRUG

comparator

Donepezil

Placebo DRUG

comparator

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects and their caregivers must provide informed consent prior to study entry.
• Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with a documented 6-month history of AD symptoms
• Subjects must have a regular caregiver who is willing to attend visits, oversee the subject's compliance with the study and report on the subject's status.
• Female subjects of child-bearing potential must agree to pregnancy testing and approved form of birth control.

You may not qualify if:

• Diagnosis of possible, probable or definite vascular dementia.
• History/evidence of any other CNS disorder that could be interpreted as a cause of dementia
• History of known or suspected seizures, loss of consciousness or significant head trauma
• Subjects with ECG, blood pressure and laboratory values outside of protocol criteria are excluded.
• Subjects with known photosensitivity
• Subjects with a history of previous exposure to SB-742457, taking agents for which there is a theoretical risk of interaction with SB-742457, or taking medication for Alzheimer's disease or centrally acting agents which might impact study outcomes may not participate.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (72)

GSK Investigational Site

Shumen, 9700, Bulgaria

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GSK Investigational Site

Sofia, 1113, Bulgaria

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GSK Investigational Site

Sofia, 1431, Bulgaria

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GSK Investigational Site

Varna, 9010, Bulgaria

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GSK Investigational Site

Viña del Mar, Región de Valparaíso, 252-0997, Chile

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GSK Investigational Site

Santiago, Región Metro de Santiago, 7510186, Chile

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GSK Investigational Site

Santiago, Región Metro de Santiago, 7560356, Chile

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GSK Investigational Site

Santiago, Chile

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GSK Investigational Site

Brno, 656 91, Czechia

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GSK Investigational Site

Olomouc, 775 20, Czechia

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GSK Investigational Site

Prague, 100 00, Czechia

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GSK Investigational Site

Prague, 10000, Czechia

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GSK Investigational Site

Prague, 110 00, Czechia

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GSK Investigational Site

Prague, 120 00, Czechia

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GSK Investigational Site

Tallinn, 10138, Estonia

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GSK Investigational Site

Tallinn, 10617, Estonia

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GSK Investigational Site

Tartu, 51014, Estonia

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GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70178, Germany

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GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

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GSK Investigational Site

Munich, Bavaria, 80331, Germany

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GSK Investigational Site

Munich, Bavaria, 81675, Germany

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GSK Investigational Site

Neuburg an der Donau, Bavaria, 86633, Germany

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GSK Investigational Site

Nuremberg, Bavaria, 90402, Germany

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GSK Investigational Site

Unterhaching, Bavaria, 82008, Germany

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GSK Investigational Site

Bad Homburg, Hesse, 61348, Germany

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GSK Investigational Site

Erbach im Odenwald, Hesse, 64711, Germany

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GSK Investigational Site

Hüttenberg, Hesse, 35625, Germany

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GSK Investigational Site

Achim, Lower Saxony, 28832, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30559, Germany

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GSK Investigational Site

Bochum, North Rhine-Westphalia, 44805, Germany

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GSK Investigational Site

Bochum, North Rhine-Westphalia, 44892, Germany

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GSK Investigational Site

Cologne, North Rhine-Westphalia, 50935, Germany

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GSK Investigational Site

Duisburg, North Rhine-Westphalia, 47051, Germany

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GSK Investigational Site

Düren, North Rhine-Westphalia, 52349, Germany

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GSK Investigational Site

Hattingen, North Rhine-Westphalia, 45525, Germany

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GSK Investigational Site

Siegen, North Rhine-Westphalia, 57072, Germany

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GSK Investigational Site

Dresden, Saxony, 01097, Germany

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GSK Investigational Site

Leipzig, Saxony, 04107, Germany

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GSK Investigational Site

Leipzig, Saxony, 04157, Germany

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GSK Investigational Site

Hamburg, 20249, Germany

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GSK Investigational Site

Athens, 115 21, Greece

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GSK Investigational Site

Athens, 11528, Greece

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GSK Investigational Site

Athens, Greece

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GSK Investigational Site

Melíssia, 151 27, Greece

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GSK Investigational Site

Thessaloniki, 57010, Greece

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GSK Investigational Site

Aguascalientes, Ags, Aguascalientes, 20127, Mexico

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GSK Investigational Site

Tijuana, Baja California Norte, 22320, Mexico

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GSK Investigational Site

Saltillo, Coahuila, 25000, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64660, Mexico

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GSK Investigational Site

Mexico City, 06700, Mexico

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GSK Investigational Site

Mexico City, 14050, Mexico

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GSK Investigational Site

Bydgoszcz, 85-094, Poland

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GSK Investigational Site

Bydgoszcz, 85-796, Poland

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GSK Investigational Site

Mosina, 62-050, Poland

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GSK Investigational Site

Poznan, 61-298, Poland

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GSK Investigational Site

Sopot, 81-824, Poland

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GSK Investigational Site

Warsaw, 02-097, Poland

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GSK Investigational Site

Moscow, 115522, Russia

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GSK Investigational Site

Moscow, 115552, Russia

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GSK Investigational Site

Moscow, 117049, Russia

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GSK Investigational Site

Saint Petersburg, 198103, Russia

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GSK Investigational Site

Durban, 4001, South Africa

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GSK Investigational Site

Loeventstein, 7530, South Africa

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GSK Investigational Site

Oakdale, 7530, South Africa

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GSK Investigational Site

Pretoria, 0181, South Africa

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GSK Investigational Site

Rosebank, 2196, South Africa

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GSK Investigational Site

Sunninghill, 2157, South Africa

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GSK Investigational Site

Busan, 602-715, South Korea

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GSK Investigational Site

Seoul, 133-792, South Korea

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GSK Investigational Site

Seoul, 135-710, South Korea

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GSK Investigational Site

Seoul, 138-736, South Korea

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GSK Investigational Site

Seoul, 158-710, South Korea

Location

Related Publications (1)

• Maher-Edwards G, Watson C, Ascher J, Barnett C, Boswell D, Davies J, Fernandez M, Kurz A, Zanetti O, Safirstein B, Schronen JP, Zvartau-Hind M, Gold M. Two randomized controlled trials of SB742457 in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2015 May 7;1(1):23-36. doi: 10.1016/j.trci.2015.04.001. eCollection 2015 Jun.

  PMID: 29854923 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

3-benzenesulfonyl-8-piperazin-1-ylquinoline; Donepezil

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2008
• First Posted: July 2, 2008
• Study Start: July 4, 2008
• Primary Completion: March 1, 2010
• Study Completion: March 9, 2010
• Last Updated: July 27, 2018
• Results First Posted: February 12, 2018

Record last verified: 2018-05

Locations

CL (4); PL (6); GR (5); KR (5); CZ (6); ME (6); DE (23); RU (4); BU (4); ZA (6); ES (3)