A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease

NCT00710684 | Completed Phase 2 Results

• 1 other identifier: AZ3110866
• Study Type: interventional
• Target: 682
• Locations: 9 countries
• Sites: 102

Brief Summary

The study is designed to investigate the safety and efficacy of SB-742457 when added to stable donepezil treatment in subjects with mild-to-moderate 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 assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the case report form (CRF) for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean is presented.

  Baseline(Week 0) and Week 24

• Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24

  The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

  Baseline(Week 0) and Week 24

Secondary Outcomes (15)

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

  Baseline (Week 0) and Week 24

• Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48

  Baseline (Week 0) and Week 12, 36 and 48

• Change From Baseline in CDR-SB Score at Week 12, 36 and 48

  Baseline (Week 0) and Week 12, 36, 48

• Change From Baseline in RBANS Score at Week 12, 36 and 48

  Baseline (Week 0) and Week 12, 36 and 48

• Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48

  Baseline (Week 0) and Week 12, 24, 36 and 48

Study Arms (3)

DONEPEZIL + SB-742457 15 MG

EXPERIMENTAL

SB-742457 - 15mg added to existing donepezil treatment

Drug: SB-742457 15mg; Drug: donepezil 5-10mg

DONEPEZIL + PLACEBO

PLACEBO COMPARATOR

Placebo added to existing donepezil

Drug: Placebo; Drug: donepezil 5-10mg

DONEPEZIL + SB-742457 35 MG

EXPERIMENTAL

SB-742457 - 35mg added to existing donepezil

Drug: SB-742457 35mg; Drug: donepezil 5-10mg

Interventions

SB-742457 15mg DRUG

SB-742457 - 15mg added to existing donepezil treatment

DONEPEZIL + SB-742457 15 MG

SB-742457 35mg DRUG

SB-742457 - 35mg added to existing donepezil

DONEPEZIL + SB-742457 35 MG

Placebo DRUG

Placebo added to existing donepezil

DONEPEZIL + PLACEBO

donepezil 5-10mg DRUG

existing donepezil treatment

DONEPEZIL + PLACEBO; DONEPEZIL + SB-742457 15 MG; DONEPEZIL + SB-742457 35 MG

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 no evidence of disorders that are thought to be the cause of, or contributing to the severity of the subject's dementia and a documented history of at least 6 months of ongoing donepezil therapy with stable dosing for at least the last 2 months.
• 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 abstinence or an approved form of birth control.
• Subjects must have adequate blood pressure and laboratory values.

You may not qualify if:

• Subjects with a diagnosis of possible, probable or definite vascular dementia may not participate.
• Subjects with known hypersensitivity to sunlight or a history of seizures, 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 (102)

GSK Investigational Site

Litchfield Park, Arizona, 85340, United States

Location

GSK Investigational Site

Fresno, California, 93720, United States

Location

GSK Investigational Site

Rancho Mirage, California, 92270, United States

Location

GSK Investigational Site

San Francisco, California, 94109, United States

Location

GSK Investigational Site

Hallandale, Florida, 33009, United States

Location

GSK Investigational Site

Hialeah, Florida, 33016, United States

Location

GSK Investigational Site

Paterson, New Jersey, 08759, United States

Location

GSK Investigational Site

Syracuse, New York, 13210, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27103, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Tulsa, Oklahoma, 74104, United States

Location

GSK Investigational Site

Memphis, Tennessee, 38119, United States

Location

GSK Investigational Site

Austin, Texas, 78757, United States

Location

GSK Investigational Site

Bennington, Vermont, 05201, United States

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1022AAO, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1405BCH, Argentina

Location

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1431FWO, Argentina

Location

GSK Investigational Site

La Plata, Buenos Aires, B1900AVG, Argentina

Location

GSK Investigational Site

Córdoba, Córdoba Province, 5000, Argentina

Location

GSK Investigational Site

Buenos Aires, 1425, Argentina

Location

GSK Investigational Site

Santa Fe, 3000, Argentina

Location

GSK Investigational Site

Kogarah, New South Wales, 2217, Australia

Location

GSK Investigational Site

Herston, Queensland, 4029, Australia

Location

GSK Investigational Site

Woodville, South Australia, 5011, Australia

Location

GSK Investigational Site

Ballarat, Victoria, 3350, Australia

Location

GSK Investigational Site

Heidelberg West, Victoria, 3084, Australia

Location

GSK Investigational Site

Kew, Victoria, 3101, Australia

Location

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

GSK Investigational Site

Saint John, New Brunswick, E2L 3L6, Canada

Location

GSK Investigational Site

Kentville, Nova Scotia, B4N 4K9, Canada

Location

GSK Investigational Site

Ottawa, Ontario, K1G 4G3, Canada

Location

GSK Investigational Site

Peterborough, Ontario, K9H 2P4, Canada

Location

GSK Investigational Site

Toronto, Ontario, M3B 2S7, Canada

Location

GSK Investigational Site

Toronto, Ontario, M6M 3Z5, Canada

Location

GSK Investigational Site

Greenfield Park, Quebec, J4V 2J2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H1T 2M4, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 1Z1, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1J 3H5, Canada

Location

GSK Investigational Site

Québec, G1R 3X5, Canada

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7510186, Chile

Location

GSK Investigational Site

Santiago, Región Metro de Santiago, 7560356, Chile

Location

GSK Investigational Site

Santiago, Chile

Location

GSK Investigational Site

Mělník, 27601, Czechia

Location

GSK Investigational Site

Olomouc, 775 20, Czechia

Location

GSK Investigational Site

Ostrava, 702 00, Czechia

Location

GSK Investigational Site

Pardubice, 53203, Czechia

Location

GSK Investigational Site

Pilsen, 301 00, Czechia

Location

GSK Investigational Site

Prague, 10000, Czechia

Location

GSK Investigational Site

Prague, 110 00, Czechia

Location

GSK Investigational Site

Prague, 14059, Czechia

Location

GSK Investigational Site

Ellwangen, Baden-Wurttemberg, 73479, Germany

Location

GSK Investigational Site

Stuttgart, Baden-Wurttemberg, 70176, Germany

Location

GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89075, Germany

Location

GSK Investigational Site

Alzenau in Unterfranken, Bavaria, 63755, Germany

Location

GSK Investigational Site

Günzburg, Bavaria, 89312, Germany

Location

GSK Investigational Site

Munich, Bavaria, 81675, Germany

Location

GSK Investigational Site

Regensburg, Bavaria, 93053, Germany

Location

GSK Investigational Site

Unterhaching, Bavaria, 82008, Germany

Location

GSK Investigational Site

Bad Homburg, Hesse, 61348, Germany

Location

GSK Investigational Site

Achim, Lower Saxony, 28832, Germany

Location

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19053, Germany

Location

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19055, Germany

Location

GSK Investigational Site

Aachen, North Rhine-Westphalia, 52062, Germany

Location

GSK Investigational Site

Bad Honnef, North Rhine-Westphalia, 53604, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44869, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01097, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01309, Germany

Location

GSK Investigational Site

Jena, Thuringia, 07743, Germany

Location

GSK Investigational Site

Berlin, 10961, Germany

Location

GSK Investigational Site

Berlin, 12163, Germany

Location

GSK Investigational Site

Berlin, 13439, Germany

Location

GSK Investigational Site

Chieti Scalo, Abruzzo, 66013, Italy

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

San Felice A Cancello - Caserta, Campania, 81027, Italy

Location

GSK Investigational Site

Cassino (FR), Lazio, 03043, Italy

Location

GSK Investigational Site

Rome, Lazio, 00148, Italy

Location

GSK Investigational Site

Rome, Lazio, 00163, Italy

Location

GSK Investigational Site

Brescia, Lombardy, 25125, Italy

Location

GSK Investigational Site

Castellanza (VA), Lombardy, 21053, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20122, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20132, Italy

Location

GSK Investigational Site

Rho, Lombardy, 20017, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10126, Italy

Location

GSK Investigational Site

Lido Di Camaiore (LU), Tuscany, 55043, Italy

Location

GSK Investigational Site

Pisa, Tuscany, 56126, Italy

Location

GSK Investigational Site

Perugia, Umbria, 06156, Italy

Location

GSK Investigational Site

Valdagno (VI), Veneto, 36078, Italy

Location

GSK Investigational Site

Verona, Veneto, 37126, Italy

Location

GSK Investigational Site

Baracaldo/Vizcaya, 48903, Spain

Location

GSK Investigational Site

Barcelona, 08003, Spain

Location

GSK Investigational Site

Barcelona, 08014, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Burgos, 09006, Spain

Location

GSK Investigational Site

Castellon, 12004, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Murcia, 30120, Spain

Location

GSK Investigational Site

Salamanca, 37007, Spain

Location

GSK Investigational Site

San Sebastián, 20014, Spain

Location

GSK Investigational Site

San Vicente Del Raspeig/Alicante, 03690, Spain

Location

GSK Investigational Site

Valencia, 46010, Spain

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 4, 2008
• Study Start: July 1, 2008
• Primary Completion: May 21, 2010
• Study Completion: November 16, 2010
• Last Updated: December 7, 2017
• Results First Posted: December 7, 2017

Record last verified: 2017-11

Locations

CA (11); ES (12); US (14); AR (7); CL (4); CZ (8); DE (22); AU (7); IT (17)