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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00710684
First Posted: July 4, 2008
Last Update Posted: December 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
Results First Submitted: August 18, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: SB-742457 15mg
Drug: SB-742457 35mg
Drug: Placebo
Drug: donepezil 5-10mg

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 684 participants were randomized from 100 centers i.e. Australia, Argentina, Chile, Canada, United States of America, Czech Republic, Spain, Italy, Germany between 01 July 2008 and 16 November 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of 1132 participants screened, 725 entered into 4-week placebo run-in period out of which 41 participants were placebo run-in failures. Out of 684 participants randomized, 682 were included in safety population (1 participant each from Donepezil+Placebo and Donepezil+SB742457 35 milligram [mg] group failed to take a dose of study medication).

Reporting Groups
  Description
Donepezil + Placebo Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Donepezil + SB-742457 15 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Donepezil + SB-742457 35 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.

Participant Flow:   Overall Study
    Donepezil + Placebo   Donepezil + SB-742457 15 mg   Donepezil + SB-742457 35 mg
STARTED   225   221   236 
COMPLETED   151   147   172 
NOT COMPLETED   74   74   64 
Adverse Event                11                19                16 
Lack of Efficacy                4                3                5 
Protocol Violation                5                5                5 
Lost to Follow-up                4                6                7 
Physician Decision                0                2                4 
Withdrawal by Subject                24                18                11 
Missing                1                0                0 
Did not continue after week 24                25                21                16 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Out of 682 participants, 5 participants did not have at least one post-Baseline or health outcomes assessment. Hence a total of 677 participants were included in intent-to-treat (ITT) population and they were used to assess Baseline characteristics.

Reporting Groups
  Description
Donepezil + Placebo Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Donepezil + SB-742457 15 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Donepezil + SB-742457 35 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Total Total of all reporting groups

Baseline Measures
   Donepezil + Placebo   Donepezil + SB-742457 15 mg   Donepezil + SB-742457 35 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 223   218   236   677 
Age 
[Units: Years]
Mean (Standard Deviation)
 73.1  (7.49)   74.2  (6.82)   73.8  (6.92)   73.7  (7.09) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      129  57.8%      118  54.1%      148  62.7%      395  58.3% 
Male      94  42.2%      100  45.9%      88  37.3%      282  41.7% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
       
American Indian or Alaska Native      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Asian      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Black or African American      0   0.0%      3   1.4%      2   0.8%      5   0.7% 
White      223 100.0%      215  98.6%      233  98.7%      671  99.1% 
More than one race      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      0   0.0%      0   0.0%      1   0.4%      1   0.1% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) Total Score at Week 24   [ Time Frame: Baseline(Week 0) and Week 24 ]

2.  Primary:   Change From Baseline in Clinical Dementia Rating – Sum of Boxes (CDR-SB) Score at Week 24   [ Time Frame: Baseline(Week 0) and Week 24 ]

3.  Secondary:   Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24   [ Time Frame: Baseline (Week 0) and Week 24 ]

4.  Secondary:   Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48   [ Time Frame: Baseline (Week 0) and Week 12, 36 and 48 ]

5.  Secondary:   Change From Baseline in CDR-SB Score at Week 12, 36 and 48   [ Time Frame: Baseline (Week 0) and Week 12, 36, 48 ]

6.  Secondary:   Change From Baseline in RBANS Score at Week 12, 36 and 48   [ Time Frame: Baseline (Week 0) and Week 12, 36 and 48 ]

7.  Secondary:   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   [ Time Frame: Baseline (Week 0) and Week 12, 24, 36 and 48 ]

8.  Secondary:   Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48   [ Time Frame: Baseline (Week 0) and Week 24 and 48 ]

9.  Secondary:   Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase   [ Time Frame: Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal) ]

10.  Secondary:   Number of Participants With Parameters of Clinical Concern - Hematology   [ Time Frame: Up to Week 48 ]

11.  Secondary:   Number of Participants With Parameters of Clinical Concern - Clinical Chemistry   [ Time Frame: Up to Week 48 ]

12.  Secondary:   Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss)   [ Time Frame: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 ]

13.  Secondary:   Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss)   [ Time Frame: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 ]

14.  Secondary:   Exposure Estimates for Donepezil (Cavgss)   [ Time Frame: Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 ]

15.  Secondary:   Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene   [ Time Frame: Baseline (Week 0) to Week 24 and Week 48 ]

16.  Secondary:   Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene   [ Time Frame: Baseline (Week 0) to Week 24 and Week 48 ]

17.  Secondary:   Change From Baseline in RBANS Scale in Participants With APOE4 Gene   [ Time Frame: Baseline (Week 0) to Week 24 and Week 48 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343



Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00710684     History of Changes
Other Study ID Numbers: AZ3110866
First Submitted: June 30, 2008
First Posted: July 4, 2008
Results First Submitted: August 18, 2017
Results First Posted: December 7, 2017
Last Update Posted: December 7, 2017