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Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy In Subjects With Mild To Moderate Alzheimer's Disease (REFLECT-3)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00348140
First Posted: July 4, 2006
Last Update Posted: September 4, 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: April 21, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: Rosiglitazone Extended Release 2mg
Drug: Rosiglitazone Extended Release 8mg
Other: Placebo

  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 1485 participants with Alzheimer’s disease (AD) who were being treated with an approved Acetylcholinesterase inhibitor (AChEI) were randomized in the study and stratified by Apolipoprotein E gene (APOE) ε4 allele status. Total of 1468 were included in safety population and 1429 in the intent-to-treat population (ITT).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Placebo Participants randomized to this arm received matching Rosiglitazone extended release (RSG XR) placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
RSG XR 2mg Participants randomized to this arm received RSG XR 2 milligrams (mg) once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
RSG XR 8mg Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)

Participant Flow:   Overall Study
    Placebo   RSG XR 2mg   RSG XR 8mg
STARTED   487   490   491 
COMPLETED   361   351   328 
NOT COMPLETED   126   139   163 
Adverse Event                46                49                78 
Lost to Follow-up                4                4                4 
Protocol Violation                12                13                14 
Withdrawal by Subject                32                40                40 
Non-compliance                8                13                5 
Participant at risk due to study drug                2                0                0 
Conditional medication increased dose                1                0                0 
Caregiver related                4                7                3 
Participant hospitalised                3                0                0 
Efficacy related                1                1                0 
Administration related                3                1                1 
Unmet inclusion-exclusion criteria                1                0                1 
Participant unwell                1                0                0 
Screen failure                1                0                0 
Investigator decided to discontinue                4                1                4 
Decided to discontinue on their own                1                4                1 
Use of prohibited drug                1                0                2 
Disease progression                1                2                5 
Increased risk of cardiac infarction                0                1                0 
Serious adverse event                0                1                0 
Abnormal ECG                0                1                3 
Participant died                0                1                0 
Exclusion criteria met                0                0                1 
Memory declined                0                0                1 



  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.
No text entered.

Reporting Groups
  Description
Placebo Participants randomized to this arm received matching RSG XR placebo tablets once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
RSG XR 2mg Participants randomized to this arm received RSG XR 2 mg once daily which remained constant throughout the 48 Week treatment period. From Week 48 all the participants received single-blind placebo treatment as one tablet daily until Visit 10 (Week 54)
RSG XR 8mg Participants randomized to this arm received RSG XR 8 mg one 4mg tablet once daily for the first 4 weeks of treatment. From Visit 3 (Week 4) onwards, these participants received one 8mg tablet once daily for the remaining 44 weeks of double-blind treatment. From Week 48 all participants received single-blind placebo treatment as one tablet daily, until Visit 10 (Week 54)
Total Total of all reporting groups

Baseline Measures
   Placebo   RSG XR 2mg   RSG XR 8mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 487   490   491   1468 
Age 
[Units: Years]
Mean (Standard Deviation)
 72.8  (8.19)   73.4  (8.19)   73.6  (8.40)   73.3  (8.26) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      272  55.9%      276  56.3%      268  54.6%      816  55.6% 
Male      215  44.1%      214  43.7%      223  45.4%      652  44.4% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
       
Hispanic or Latino   16   14   18   48 
Not Hispanic or Latino   467   473   470   1410 
Missing   4   3   3   10 


  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 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort   [ Time Frame: Baseline (Week 0) and Week 48 ]

2.  Primary:   Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort   [ Time Frame: Baseline (Week 0) and Week 48 ]

3.  Primary:   Change From Baseline in ADAS-Cog Total Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort   [ Time Frame: Baseline (Week 0) and Week 48 ]

4.  Primary:   Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score at Week 48, as a Function of APOE ε4 Status in APOE4 Negatives Cohort   [ Time Frame: Baseline (Week 0) and Week 48 ]

5.  Primary:   Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in All Except E4/E4s Cohort   [ Time Frame: Baseline (Week 0) and Week 48 ]

6.  Primary:   Change From Baseline in CDR-SB Score at Week 48, as a Function of APOE ε4 Status in Full Population Cohort   [ Time Frame: Baseline (Week 0) and Week 48 ]

7.  Secondary:   Change From Baseline in ADAS-Cog Total Score at Weeks 8, 16, 24 and 36   [ Time Frame: Baseline (Week 0) and Week 8, 16, 24, 36 ]

8.  Secondary:   Change From Baseline in CDR-SB Score at Weeks 12, 24 and 36   [ Time Frame: Baseline (Week 0) and Week 12, 24, 36 ]

9.  Secondary:   Change From Screening in Mini Mental State Examination (MMSE) Total Score   [ Time Frame: Screening (Week -4) and Week 48 ]

10.  Secondary:   Change From Baseline in Disability Assessment for Dementia (DAD) Total Score   [ Time Frame: Baseline (Week 0) and Week 8, 16, 24, 48 ]

11.  Secondary:   Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score   [ Time Frame: Baseline (Week 0) and Week 8, 16, 24, 48 ]

12.  Secondary:   Change From Baseline in Domains of the Resource Utilization in Dementia Scale (RUD)- Q1 and Q2 Caregiver Hours   [ Time Frame: Baseline (Week 0) and Week 12, 24, 36, 48 ]

13.  Secondary:   Change From Baseline in European Quality of Life -5 Dimensions (EQ-5D) Scale Total Score- Thermometer Score   [ Time Frame: Baseline (Week 0) and Week 12, 36, 48 ]

14.  Secondary:   Change From Baseline in EQ-5D Scale Total Score- Utility Score   [ Time Frame: Baseline (Week 0) and Week 12, 36, 48 ]

15.  Secondary:   Change From Baseline in Alzheimer’s Carer’s Quality of Life Instrument (ACQLI) Score   [ Time Frame: Baseline (Week 0) and Week 12, 36, 48 ]

16.  Secondary:   Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48   [ Time Frame: Week 48 and Week 54 ]

17.  Secondary:   Change in CDR-SB Total Score for Observed Cases at Week 54 Compared to Week 48   [ Time Frame: Week 48 and Week 54 ]

18.  Secondary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48   [ Time Frame: Baseline (Week 0) and Week 48 ]

19.  Secondary:   Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Severity of AEs   [ Time Frame: Upto Week 48 ]

20.  Secondary:   Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Weight   [ Time Frame: Upto Week 54 ]

21.  Secondary:   Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: Upto Week 54 ]

22.  Secondary:   Number of Participants With Change From Baseline in Vital Signs of Clinical Concern at Any Time on Treatment- Heart Rate (HR)   [ Time Frame: Upto Week 54 ]

23.  Secondary:   Change From Baseline in Weight   [ Time Frame: Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, 36, 48, 54 ]

24.  Secondary:   Change From Baseline in Hemoglobin   [ Time Frame: Baseline (Week 0) and Weeks 4, 16, 36, 48 ]

25.  Secondary:   Change From Baseline in Hematocrit   [ Time Frame: Baseline (Week 0) and Weeks 4, 16, 36, 48 ]

26.  Secondary:   Any Time on Treatment Differences in Frequencies of Hematology Data Outside the Reference Range   [ Time Frame: Up to Week 48 ]

27.  Secondary:   Any Time on Treatment Differences in Frequencies of Clinical Chemistry Data Outside the Reference Range   [ Time Frame: Upto Week 48 ]

28.  Secondary:   Changes From Baseline in Electrocardiogram (ECG) Parameters- HR   [ Time Frame: Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54 ]

29.  Secondary:   Changes From Baseline in ECG Parameters- RR Interval, QT Interval, QTcB, QTcF, PR Interval and QRS Duration   [ Time Frame: Baseline (Week 0) and Weeks 4, 8, 16, 24, 36, 48, 54 ]

30.  Secondary:   Change From Baseline in HbA1c up to Week 54   [ Time Frame: Baseline (Week 0) and Weeks 12, 24, 36, 48, 54 ]

31.  Secondary:   Change From Baseline in Short Term Memory Assessment   [ Time Frame: Baseline (Week 0) and upto 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


Publications:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00348140     History of Changes
Other Study ID Numbers: AVA102670
First Submitted: June 30, 2006
First Posted: July 4, 2006
Results First Submitted: April 21, 2017
Results First Posted: September 4, 2017
Last Update Posted: September 4, 2017