Rosiglitazone (Extended Release Tablets) As Monotherapy In Subjects With Mild To Moderate Alzheimer's Disease

April 13, 2017 updated by: GlaxoSmithKline

A 24-week, Double-blind, Double-dummy, Randomized, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets), Donepezil, and Placebo as Monotherapy on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease. (REFLECT-1)

Rosiglitazone (RSG) has been tested and is approved as a treatment for type II diabetes mellitus, a disease that occurs when the body ineffectively uses glucose. RSG XR, the investigational drug, is an extended-release form of RSG. This study tests whether RSG XR safely provides benefit to people with mild to moderate Alzheimer's disease (AD). RSG XR is a new approach to AD therapy and this study tests whether one's genes alter the effectiveness of RSG XR. Glucose is used by cells to make energy that they need to live. Changes in the ability of cells to use of glucose can lead to diseases like diabetes. Glucose levels may be lower in the brains of AD patients, and their brain cells may also use glucose less well than in unaffected people. The proper function of brain cells may be critical to memory and thought. If brain cells use glucose poorly, this might impact AD. Drugs that help brain cells properly use glucose may help a person maintain normal memory and thinking. Data suggesting that RSG may help AD patients was first seen in a small study at the Univ. of Washington and then from a larger international GSK study. In the first study, those receiving RSG once daily for 6 months scored better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that benefited most from therapy with RSG XR had a specific genetic pattern. They lacked the gene that caused them to produce apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene from one parent. Subjects with one copy of the APOE e4 gene remained fairly stable while those with two copies of APOE e4 continued to worsen during the 6-month treatment. This study will directly test the effect of RSG XR on people who either have or lack the APOE e4 gene.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

A 24-week, double-blind, double-dummy, randomized, parallel-group study to investigate the effects of rosiglitazone (extended release tablets), donepezil, and placebo as monotherapy on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease. (REFLECT-1)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
862

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz-Eggenberg, Austria, A-8020
        • GSK Investigational Site
      • Hall in Tirol, Austria, A-6060
        • GSK Investigational Site
      • Linz, Austria, A-4020
        • GSK Investigational Site
      • Linz, Austria, 4020
        • GSK Investigational Site
      • Vienna, Austria, A-1090
        • GSK Investigational Site
      • Vienna, Austria, 1030
        • GSK Investigational Site
      • Vienna, Austria, A-1130
        • GSK Investigational Site
  • Bulgaria
      • Plovdiv, Bulgaria, 4000
        • GSK Investigational Site
      • Sofia, Bulgaria, 1431
        • GSK Investigational Site
      • Sofia, Bulgaria, 1527
        • GSK Investigational Site
      • Sofia, Bulgaria, 1113
        • GSK Investigational Site
  • Chile
    • Región Metro De Santiago
      • Providencia / Santiago, Región Metro De Santiago, Chile, 7500710
        • GSK Investigational Site
      • Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
        • GSK Investigational Site
      • Santiago, Región Metro De Santiago, Chile, 7560356
        • GSK Investigational Site
    • Valparaíso
      • Viña del Mar, Valparaíso, Chile, 252-0997
        • GSK Investigational Site
  • China
      • Beijing, China, 100730
        • GSK Investigational Site
      • Beijing, China, 100083
        • GSK Investigational Site
      • Shanghai, China, 200025
        • GSK Investigational Site
      • Shanghai, China, 200040
        • GSK Investigational Site
      • Shanghai, China, 200030
        • GSK Investigational Site
      • Tianjin, China, 300052
        • GSK Investigational Site
    • Guangdong
      • Guangzhou, Guangdong, China, 510370
        • GSK Investigational Site
  • Croatia
      • Dubrovnik, Croatia, 20000
        • GSK Investigational Site
      • Zagreb, Croatia, 10000
        • GSK Investigational Site
  • Estonia
      • Tallinn, Estonia, 10617
        • GSK Investigational Site
      • Tallinn, Estonia, 10138
        • GSK Investigational Site
      • Tallinn, Estonia, 10614
        • GSK Investigational Site
      • Tartu, Estonia, 51014
        • GSK Investigational Site
  • Germany
      • Berlin, Germany, 13125
        • GSK Investigational Site
      • Berlin, Germany, 12167
        • GSK Investigational Site
      • Berlin, Germany, 12163
        • GSK Investigational Site
      • Berlin, Germany, 13507
        • GSK Investigational Site
      • Berlin, Germany, 14163
        • GSK Investigational Site
      • Hamburg, Germany, 22143
        • GSK Investigational Site
      • Hamburg, Germany, 20249
        • GSK Investigational Site
      • Hamburg, Germany, 22083
        • GSK Investigational Site
    • Baden-Wuerttemberg
      • Ellwangen, Baden-Wuerttemberg, Germany, 73479
        • GSK Investigational Site
      • Tuebingen, Baden-Wuerttemberg, Germany, 72076
        • GSK Investigational Site
      • Ulm, Baden-Wuerttemberg, Germany, 89073
        • GSK Investigational Site
      • Ulm, Baden-Wuerttemberg, Germany, 89075
        • GSK Investigational Site
    • Bayern
      • Guenzburg, Bayern, Germany, 89312
        • GSK Investigational Site
      • Muenchen, Bayern, Germany, 81675
        • GSK Investigational Site
      • Muenchen, Bayern, Germany, 80331
        • GSK Investigational Site
      • Nuernberg, Bayern, Germany, 90402
        • GSK Investigational Site
      • Unterhaching, Bayern, Germany, 82008
        • GSK Investigational Site
    • Hessen
      • Bad Homburg, Hessen, Germany, 61348
        • GSK Investigational Site
    • Mecklenburg-Vorpommern
      • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
        • GSK Investigational Site
      • Schwerin, Mecklenburg-Vorpommern, Germany, 19053
        • GSK Investigational Site
    • Niedersachsen
      • Achim, Niedersachsen, Germany, 28832
        • GSK Investigational Site
      • Hannover, Niedersachsen, Germany, 30559
        • GSK Investigational Site
    • Nordrhein-Westfalen
      • Baesweiler, Nordrhein-Westfalen, Germany, 52499
        • GSK Investigational Site
      • Bielefeld, Nordrhein-Westfalen, Germany, 33647
        • GSK Investigational Site
      • Bochum, Nordrhein-Westfalen, Germany, 44892
        • GSK Investigational Site
      • Duisburg, Nordrhein-Westfalen, Germany, 47051
        • GSK Investigational Site
      • Juelich, Nordrhein-Westfalen, Germany, 52428
        • GSK Investigational Site
      • Koeln, Nordrhein-Westfalen, Germany, 50767
        • GSK Investigational Site
    • Sachsen
      • Chemnitz, Sachsen, Germany, 09111
        • GSK Investigational Site
      • Dresden, Sachsen, Germany, 01307
        • GSK Investigational Site
      • Dresden, Sachsen, Germany, 01097
        • GSK Investigational Site
      • Leipzig, Sachsen, Germany, 04103
        • GSK Investigational Site
    • Sachsen-Anhalt
      • Halle, Sachsen-Anhalt, Germany, 06122
        • GSK Investigational Site
    • Schleswig-Holstein
      • Itzehoe, Schleswig-Holstein, Germany, 25524
        • GSK Investigational Site
    • Thueringen
      • Gera, Thueringen, Germany, 07551
        • GSK Investigational Site
  • Greece
      • Athens, Greece, 115 21
        • GSK Investigational Site
      • Melissia, Greece, 151 27
        • GSK Investigational Site
      • Thessaloniki, Greece, 57010
        • GSK Investigational Site
  • Hungary
      • Budapest, Hungary, 1106
        • GSK Investigational Site
      • Gyula, Hungary, 5700
        • GSK Investigational Site
      • Kaposvár, Hungary, 7400
        • GSK Investigational Site
      • Pécs, Hungary, 7623
        • GSK Investigational Site
      • Szeged, Hungary, 6725
        • GSK Investigational Site
  • India
      • Bangalore, India, 560034
        • GSK Investigational Site
      • Nagpur, India, 440010
        • GSK Investigational Site
      • Tirupati, India, 517507
        • GSK Investigational Site
  • Korea, Republic of
      • Seongnam-si,, Korea, Republic of, 463-707
        • GSK Investigational Site
      • Seoul, Korea, Republic of, 143-729
        • GSK Investigational Site
  • Mexico
      • Mexico, Mexico, 14000
        • GSK Investigational Site
    • Coahuila
      • Saltillo, Coahuila, Mexico, 25000
        • GSK Investigational Site
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64660
        • GSK Investigational Site
  • New Zealand
      • Auckland, New Zealand, 0622
        • GSK Investigational Site
  • Pakistan
      • Karachi, Pakistan, 74800
        • GSK Investigational Site
      • Lahore, Pakistan, 54000
        • GSK Investigational Site
      • Lahore, Pakistan, 54590
        • GSK Investigational Site
  • Peru
      • Lima, Peru, Lima 13
        • GSK Investigational Site
  • Philippines
      • Pasig City, Philippines, 1600
        • GSK Investigational Site
      • Quezon City, Philippines, 1102
        • GSK Investigational Site
  • Puerto Rico
      • Cabo Rojo, Puerto Rico, 623
        • GSK Investigational Site
      • San Juan, Puerto Rico, 00918
        • GSK Investigational Site
      • San Juan, Puerto Rico, 90660
        • GSK Investigational Site
  • Russian Federation
      • Moscow, Russian Federation, 115522
        • GSK Investigational Site
      • Moscow, Russian Federation, 117049
        • GSK Investigational Site
      • Moscow, Russian Federation, 115552
        • GSK Investigational Site
      • St. Petersburg, Russian Federation, 197022
        • GSK Investigational Site
      • St.-Petersburg, Russian Federation, 198103
        • GSK Investigational Site
  • United Kingdom
      • Bradford, United Kingdom, BD3 0DQ
        • GSK Investigational Site
      • Derriford, Plymouth, United Kingdom, PL6 8BX
        • GSK Investigational Site
      • West of Scotland Science Park, Glasgow, United Kingdom, G20 0XA
        • GSK Investigational Site
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • GSK Investigational Site
    • California
      • Los Angeles, California, United States, 90036
        • GSK Investigational Site
      • Newport Beach, California, United States, 92660
        • GSK Investigational Site
      • Palo Alto, California, United States, 94305
        • GSK Investigational Site
      • Reseda, California, United States, 91355
        • GSK Investigational Site
      • San Diego, California, United States, 92120
        • GSK Investigational Site
      • San Francisco, California, United States, 94109
        • GSK Investigational Site
    • Colorado
      • Denver, Colorado, United States, 80218
        • GSK Investigational Site
    • Connecticut
      • Fairfield, Connecticut, United States, 06824
        • GSK Investigational Site
      • Norwalk, Connecticut, United States, 06851
        • GSK Investigational Site
    • Florida
      • Deerfield Beach, Florida, United States, 33064
        • GSK Investigational Site
      • Delray Beach, Florida, United States, 33445
        • GSK Investigational Site
      • Destin, Florida, United States, 32541
        • GSK Investigational Site
      • Hialeah, Florida, United States, 33016
        • GSK Investigational Site
      • Melbourne, Florida, United States, 32901
        • GSK Investigational Site
      • Plantation, Florida, United States, 33317
        • GSK Investigational Site
      • Sunrise, Florida, United States, 33351
        • GSK Investigational Site
      • Tampa, Florida, United States, 33647
        • GSK Investigational Site
    • Georgia
      • Atlanta, Georgia, United States, 30033
        • GSK Investigational Site
    • Minnesota
      • St. Paul, Minnesota, United States, 55101
        • GSK Investigational Site
    • Nevada
      • Las Vegas, Nevada, United States, 89146
        • GSK Investigational Site
    • New Jersey
      • Kenilworth, New Jersey, United States, 07033
        • GSK Investigational Site
      • Toms River, New Jersey, United States, 08755
        • GSK Investigational Site
    • New York
      • Albany, New York, United States, 12208
        • GSK Investigational Site
      • Syracuse, New York, United States, 13210
        • GSK Investigational Site
    • Ohio
      • Centerville, Ohio, United States, 45459
        • GSK Investigational Site
      • Cleveland, Ohio, United States, 44195
        • GSK Investigational Site
      • Cleveland, Ohio, United States, 44120
        • GSK Investigational Site
      • Toledo, Ohio, United States, 43623
        • GSK Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73112
        • GSK Investigational Site
      • Oklahoma City, Oklahoma, United States, 73118
        • GSK Investigational Site
      • Tulsa, Oklahoma, United States, 74104
        • GSK Investigational Site
    • Pennsylvania
      • Jenkintown, Pennsylvania, United States, 19046
        • GSK Investigational Site
      • Philadelphia, Pennsylvania, United States, 19102
        • GSK Investigational Site
      • Philadelphia, Pennsylvania, United States, 19104
        • GSK Investigational Site
    • Tennessee
      • Memphis, Tennessee, United States, 35105
        • GSK Investigational Site
      • Nashville, Tennessee, United States, 37212
        • GSK Investigational Site
    • Texas
      • DeSoto, Texas, United States, 75115
        • GSK Investigational Site
      • San Antonio, Texas, United States, 78229
        • GSK Investigational Site
      • San Antonio, Texas, United States, 78229-3900
        • GSK Investigational Site
    • Wisconsin
      • Middleton, Wisconsin, United States, 53562-2215
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Clinical diagnosis of probable Alzheimer's Disease (AD).
  • MMSE score 10 to 23
  • Has not taken an approved AD therapy in last 30 days.
  • No previous hypersensitivity/intolerance to AChEIs
  • Have a regular caregiver.

Exclusion criteria:

  • Diagnosis of vascular dementia.
  • Type I or secondary diabetes mellitus.
  • Type II diabetes mellitus treated with insulin, sulfonylurea or glipizide.
  • History or evidence of congestive heart failure, clinically significant peripheral edema or anemia.
  • History of significant psychiatric illness, major depressive disorder or current depression needing initiation of treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Rosiglitazone
XR (extended release) oral tablets
Drug: Rosiglitazone
XR (extended release) oral tablets
Other: Placebo
Placebo (Double-Dummy to Match)
Drug: Rosiglitazone
XR (extended release) oral tablets

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Apolipoprotein epsilon4 (APOE e4) Negative Cohort
Time Frame: Baseline (W0) and W24
The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4's Cohort
Time Frame: Baseline (W0) and W24
The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort
Time Frame: Baseline (W0) and W24
The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Items were evaluated by tests and clinician ratings on a 5-point scale. Scores ranged from 0-70 with higher scores indicates more dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in APOE4 Negative Cohort
Time Frame: Baseline (W0) and W24
The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in All Except e4/e4's Cohort
Time Frame: Baseline (W0) and W24
The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W24 as a Function of APOE e4 Status in Full Population Cohort
Time Frame: Baseline (W0) and W24
The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means greater dysfunction. It was based on interviews with the par. and caregiver by an independent rater. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. Estimated value was calculated by Active treatment minus Placebo. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the three genetic subgroups. There was no adjustment for the donepezil versus placebo comparisons, which were included to assess the sensitivity of the trial to detect a treatment effect.
Baseline (W0) and W24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline (W0) in Mean ADAS-Cog Total Score at W8, W16, W24
Time Frame: Baseline (W0) and up to W24
The 11-item 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 5-point scale. Scores ranged from 0-70 with higher scores indicating greater dysfunction. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline is defined as value at W0. Endpoint treatment differences were adjusted to take account of missing data. It was evaluated at Baseline, W8, W16 and W24.
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean CIBIC+ Global Functioning Total Score at W8, W16, W24
Time Frame: Baseline (W0) and up to W24
The CIBIC+ assessment comprised of a 7-point rating of severity (at baseline) and change (at indicated time points). It was rated on a scale of 1 to 7 as 1: markedly improved, 2.: moderately improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: moderately worse and 7: markedly worse; higher score means more dysfunction. The scale was based on interviews with the par. and caregiver and was completed by an independent rater. It required separate structured 15-20 minute interviews with the par. and caregiver. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived. It was evaluated at Baseline, W8, W16 and W24.
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean Neuropsychiatric Inventory (NPI) Total Score at W8, W16, W24
Time Frame: Baseline (W0) and up to W24
The NPI assessed behavioral disturbances comprises 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety and aberrant motor activity. The par. caregiver asked about behavior in the par. If "Yes", the informant then rates both the severity on a 3-point scale, 1: mild to 3: severe (total range: 0-36) and the frequency using a 4-point scale, 1: occasionally to 4: very frequently. The total domain score was frequency × severity. The distress was scored on 5-point scale, 0: no distress to 5 - very severe or extreme. A total NPI score can be calculated by adding all domain scores together; NPI total score: from 0-144 and NPI distress score: from 0-60, all with higher scores indicating more severe behavioral disturbance. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0.
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean Disability Assessment for Dementia (DAD) Scale Total Score at W8, W16, W24
Time Frame: Baseline (W0) and up to W24
The DAD, assessed the ability of a par. to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item was scored as yes: 1, no: 0 and N/A: not applicable. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. The percentage score was calculated as (DAD total score/total number of applicable items) multiplied by 100. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean Short Term Memory Assessment Total Score (ADAS-Cog Q1 Plus Q7) at W8, W16, W24
Time Frame: Baseline (W0) and up to W24
Change from Baseline in short term memory assessment score was assessed from a combined analysis of items 1 (word recall task) and 7 (word recognition task) of ADAS-Cog scale. Word recall task consist of the participants score was the mean number of words not recalled on three trials (maximum score 10) and word recognition task, to score this item the number of incorrect responses was counted (maximum error score was 12). Higher score indicating greater dysfunction. Total score is sum of individual score. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Utility
Time Frame: Baseline (W0) and up to W24
The EQ-5D Proxy was a 2 part scale used to assess the quality of life and utility benefit. The data for Part 1 is presented. It is a 5 dimensional Health State Classification. Caregivers were asked to respond as they feel the par. would on dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Answers to each question were recorded on a 3-point scale which indicates the level of impairment (level 1= no problem; level 2=some or moderate problem(s) and level 3=unable, or extreme problem with higher scores indicating greater dysfunction. EQ-5D Proxy assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Baseline (W0) and up to W24
Change From Baseline (W0) in Mean European Quality of Life -5 Dimensions Proxy Version (EQ-5D Proxy) Total Score at W12, W24 Assessed by Thermometer (Visual Analog Scale [VAS])
Time Frame: Baseline (W0) and up to W24
The EQ-5D Proxy is a 2 part scale used to assess the quality of life and utility benefit. The data for Part 2 is presented. It is a the visual analogue scale Thermometer which assessed caregiver's impression of par. overall health. The Thermometer has endpoints of 100 (best imaginable health state) and 0 (worst imaginable health state). EQ-5D Proxy assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Baseline (W0) and up to W24
Time Spent Caring for Basic and Instrumental Activities Resource Utilization in Dementia (RUD) Scale at W12 and W24
Time Frame: Baseline (W0) and up to W24
The RUD instrument was developed as a comprehensive tool to assess the amount of resource use among demented par. RUD assess both formal and informal resource use of the par. and the primary caregiver, making it possible to calculate costs from a societal perspective. Q1 relates to assisting par. with basic activities of daily living and Q2 relates to instrumental activities of daily living. The assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Baseline (W0) and up to W24
Change From Baseline (W0) in Alzheimer's Carer's Quality of Life Instrument (ACQLI) Score at W12 and W24.
Time Frame: Baseline (W0) and up to W24
The ACQLI was an assessment of caregiver quality of life. This instrument consists of 30 questions exploring various aspects of carer's quality of life. Each of the questions had a two point response and the 30 questions were summed to provide a total score. Items are assumed to be unidimensional (i.e., represent a single variable) and are scored 0/1 (false/true) before summation into a total score with a 0-30 range. To ease comparisons between scales, ACQLI scores were transformed to range between 0-100 (100: worse). The assessments was performed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Baseline (W0) and up to W24
Change From Baseline (W0) in Mini Mental State Examination (MMSE) Total Score at W24.
Time Frame: Baseline (W0) and W24
The MMSE consists of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment. The scale is completed by the investigator, based on the performance of the par. and takes approximately 5 to 10 minutes to administer. The assessments was performed at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived
Baseline (W0) and W24
Change From Baseline (W0) in Glycosylated Hemoglobin (HbA1c) at W24.
Time Frame: Baseline (W0) and W24
The blood sample was collected for assessments of HbA1c levels at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0. Endpoint treatment differences which were adjusted to take account of missing data are derived.
Baseline (W0) and W24
Number of Participants With Adverse Events Defined by Severity
Time Frame: Up to W24
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE included significant or unexpected worsening or exacerbation of the condition/indication under study, exacerbation of a chronic or intermittent pre-existing condition, new conditions detected or diagnosed, signs, symptoms, or the clinical sequelae of a suspected overdose of either investigational product or a concurrent medication. Number of participants with any AE and as per severity were reported. Refer to the general AE/SAE module for a list of AEs and SAEs.
Up to W24
Number of Participants With Systolic and Diastolic Blood Pressure (SBP and DBP), Heart Rate (HR) and Weight Values of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT).
Time Frame: Up to W24
SBP, DBP and HR of par. were recorded in sitting posture as vital signs, while body weight was measured without shoes and wearing light clothing at each visit. The blood pressure (BP) and HR values were identified as of PCC if the vales were out of the reference range (for SBP, 90 to 140 millimeters of mercury (mmHg), DBP, 50 to 90 mmHg, and HR >100 or <50 beats per minute [bpm]) or meet a change from Baseline criterion. For SBP it was increase from Baseline (high) if increased by more than or equal to (>=) 40 mmHg; decrease from Baseline (low) if decreased by >=30 mmHg. For DBP, increase from Baseline (high) if increased by >=30 mmHg; decrease from Baseline (low) if decreased by >=20 mmHg. For HR, increase from Baseline (high) if increased by >=30 bpm; decrease from Baseline (low) if decreased by >=30 bpm. For weight, increase from Baseline (high) if increased by >=7%; decrease from Baseline (low) if decreased by >=7%. Baseline was defined as value at W0.
Up to W24
Change From Baseline (W0) in 12-lead Electrocardiogram (ECG)
Time Frame: Baseline (W0) and up to W24
Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the par. had rested in the supine position in a quiet room (no TV, minimal talking) for at least 10 minutes. Conduction intervals from the 12-lead ECGs were manually read and confirmed by an external cardiologist/vendor. The ECG parameters includes PR interval, QRS duration, QT - uncorrected interval, QTc Bazett (QTcB), QTc Fridericia (QTcF) and RR interval of Central Cardiologist are reported. The assessments was performed at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Screening/Visit 1/W-6.
Baseline (W0) and up to W24
Change From Baseline (W0) in Heart Rate (HR) Measured From 12-lead Electrocardiogram (ECG)
Time Frame: Baseline (W0) and up to W24
Triplicate 12-lead ECG measures was obtained digitally, approximately one minute apart after the par. had rested in the supine position in a quiet room (no TV, minimal talking) for at least 10 minutes. Conduction intervals from the 12-lead ECGs were manually read and confirmed by an external cardiologist/vendor. The ECG HR of Central Cardiologist reported. The assessments was performed at Baseline and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Screening/Visit 1/W-6.
Baseline (W0) and up to W24
Change From Baseline (W0) in Body Weight
Time Frame: Baseline (W0) and up to W24
Body weight will be measured at all visits, without shoes and wearing light clothing. The assessments was performed at Baseline, W4, W8, W12, W16, and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0.
Baseline (W0) and up to W24
Change From Baseline (W0) in Hemoglobin
Time Frame: Baseline (W0) and up to W24
Hematology parameters were assessed at Baseline, W4, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0.
Baseline (W0) and up to W24
Change From Baseline (W0) in Hematocrit
Time Frame: Baseline (W0) and Up to W24
Hematology parameters were assessed at Baseline, W4, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0.
Baseline (W0) and Up to W24
Change From Baseline (W0) in Periodic HbA1c Assessment
Time Frame: Baseline (W0) and up to W24
HbA1c assessment was performed par. with type 2 diabetes mellitus or HbA1c >=6.5% at Screening only. HbA1c levels were assessed at Baseline, W12 and W24. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at W0.
Baseline (W0) and up to W24
Number of Par. With Hematology Data of Potential Clinical Concern Any Time on Treatment
Time Frame: Up to W24
Haematology parameters were identified as of PCC (high [H], low [L]), if the values were out of the reference range (RR). The range for parameters was: platelet (100AV-500AV), red blood cell (RBC, 0.8-1.2), hemoglobin (L: female [F]:10, male [M]:11; H: F:16.5-AV, M:18), hematocrit (0.8-1.2), white blood cell (WBC, 3-15), neutrophils (0.75-1.5), lymphocytes (0.75-1.5), monocytes (0.75-2), eosinophils (none-2), basophils (none-2), mean corpuscle volume (MCV, 0.8-1.2), mean corpuscular hemoglobin (MCH, 0.8-1.2), mean corpuscular hemoglobin concentration (MCHC, 0.8-1.2), red cell distribution width (RDW, 0.8-1.2). Data for mean platelet volume (reference range not established) not reported
Up to W24
Number of Par. With Clinical Chemistry Values of Potential Clinical Concern Any Time on Treatment
Time Frame: Up to W24
Clinical chemistry parameters were identified as of PCC (H, L), if values were out of RR: Alanine aminotransferase (ALT, none-120 [250% upper limit of RR, ULRR]), Albumin (0.75-2), Aspartate aminotransferase (AST,none-105 (3-64y), 137.5 (65+y), >250%ULRR), Alkaline phosphatase (ALP,none-312.5 (20+y), >250%ULRR), blood urea nitrogen (BUN)/Creatinine ratio (none-1.25), BUN (none-11), Chloride (80-115), Calcium (0.75-1.25), Carbon dioxide (CO2, 15-40) content, Creatinine (22, <50% lower limit of RR [LLRR]-155, >125%ULRR), Creatine phosphokinase (CPK, none-1.25), Gamma glutamyl transferase (GGT,none-2.5), Glucose (3.6-7.8), High density lipoprotein (HDL,0.65-none), Lactate dehydrogenase (LDH,none-1.25), Low density lipoprotein (LDL,none-2), Magnesium (0.5-2), Potassium (3-5.5), Phosphorus inorganic (0.5-1.5), Sodium (130-150), Total protein (0.8-1.5), Total cholesterol (none-1.25), Total bilirubin (none-1.95), Triglycerides (none-9). Data for Creatinine clearance not reported.
Up to W24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 27, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2008

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 5, 2008

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 25, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 25, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 29, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 19, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 105640

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

  1. Annotated Case Report Form
    Information identifier: 105640
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Dataset Specification
    Information identifier: 105640
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Statistical Analysis Plan
    Information identifier: 105640
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Informed Consent Form
    Information identifier: 105640
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Individual Participant Data Set
    Information identifier: 105640
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Clinical Study Report
    Information identifier: 105640
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Study Protocol
    Information identifier: 105640
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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