Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers
- Registration Number
- NCT00550420
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a Phase III, multicenter, open-label extension, single-group study in male and female outpatients with mild-to-moderate Alzheimer's disease (AD) who have completed AVA105640. All subjects will receive rosiglitazone extended-release (RSG XR) 4mg once daily for the first 4 weeks of the study followed by 8mg RSG XR. Subject participation will last until one of 5 conditions applies. After a 52-week open-label treatment phase, subjects will attend a final Follow-Up Visit 6 weeks after the end of treatment. The primary objective of this study is to evaluate the long-term safety and tolerability of RSG XR in subjects with mild-to-moderate AD who have completed AVA105640. The secondary objective of this study is to explore further the long-term efficacy of RSG XR in terms of cognitive function and overall clinical response as a function of apolipoprotein E (APOE) e4 allele status
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 331
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm 1 Rosiglitazone XR Rosiglitazone XR
- Primary Outcome Measures
Name Time Method Number of Participants With Any Adverse Events (AEs) and Severity of AEs Up to Week 82 AE was 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. The drug related-AEs of special interest (AESI) was reported. The severity of the AESI was categorized as mild, moderate and severe. Number of participants with AEs were reported for treatment duration of the study.
- Secondary Outcome Measures
Name Time Method Number of Participants With Serious AEs and Deaths Up to Week 82 A serious adverse event is defined as any untoward medical occurrence that, at any dose results in death, life-threatening condition, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or a congenital anomaly or birth defect. The SAEs and deaths are reported from Visit 1 (W0) till end of the follow-up period (W110)
Percentage of Participants With AEs of Edema Up to 82 Weeks Edema was considered as adverse event of special interest (AESI). The process for AESI selection was based on RSG's pharmacologic class and relevant AEs potentially associated with RSG. Percentage of participants reported with edema as AESI were reported.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82) SBP and DBP of participant were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the vales were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from Baseline criterion. The change from Baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (\>=) 40 mmHg from Baseline; decrease from Baseline (low) if decreased by \>= 30 mmHg from Baseline. For DBP, increase form Baseline (high) if increased by \>= 30 mmHg from Baseline; decrease from Baseline (low) if decreased by \>= 20 mmHg from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.
Change From Baseline in Heart Rate (HR) Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82) HR of participants was recorded as vital sign at each visit. The HR values were identified as of potential clinical concern if the vales were out of the reference range 50 to 100 beats per minute (BPM) or meet a change from Baseline criterion. The change from Baseline criterion was as, increase in HR (high) from Baseline if HR was increased by \>= 30 bpm or decrease in HR (Low) from Baseline if HR was decreased by \>= 30 bpm from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the HR at specified visit minus the Baseline value.
Number of Participants With Abnormal SBP and DBP at Any Time During Treatment Period Up to 82 weeks SBP and DBP of participant were recorded in sitting posture as vital sign at each visit. The blood pressure (BP) values were identified as of potential clinical concern if the vales were out of the reference range (for SBP, 90 to 140 mmHg and DBP, 50 to 90 mmHg) or meet a change from Baseline criterion. The change from Baseline criterion for SBP, was increase from Baseline (high) if increased by more than or equal to (\>=) 40 mmHg from Baseline; decrease from Baseline (low) if decreased by \>= 30 mmHg from Baseline. For DBP, increase form Baseline (high) if increased by \>= 30 mmHg from Baseline; decrease from Baseline (low) if decreased by \>= 20 mmHg from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.
Change From Baseline in Body Weight (BW) Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82) BW of participants were recorded as vital sign at each visit. The BW were identified as of potential clinical concern if the vales were increased or decreased from Baseline by \>=7%. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was measured as the BW at specified visit minus the Baseline value.
Number of Participants With Abnormal HR at Any Time During Treatment Period Up to 82 weeks HR of participants was recorded as vital sign at each visit. The HR values were identified as of potential clinical concern if the vales were out of the reference range 50 to 100 beats per minute (BPM) or meet a change from Baseline criterion. The change from Baseline criterion was as, increase in HR (high) from Baseline if HR was increased by \>= 30 bpm or decrease in HR (Low) from Baseline if HR was decreased by \>= 30 bpm from Baseline. The Baseline assessments were referred to assessments at Visit 1 (W 0). Change from Baseline was measured as the HR at specified visit minus the Baseline value. Number of participants with abnormal HR at any time during treatment period were reported.
Number of Participants With Hematological Parameters of Potential Clinical Concern Up to 82 weeks The hematological parameters including eosinophils, lymphocytes, monocytes, platelet count, Segmented Neutrophils, total neutrophils, white blood cell (WBC), red blood cell (RBC) counts, hemoglobin, hematocrit count, mean corpuscle hemoglobin (MCH) and mean corpuscle volume (MCV) were analyzed as safety parameters. The number of participants with values outside the reference range (potential clinical concern ) at any time on treatment (ATOT) and follow-up period were reported. The treatment period was till W104 followed by 6 weeks of follow-up period till W110 of study.
Mean Clinician Interview-Based Impression of Change Plus Caregiver Input (CIBIC+) Score as a Function of APOE 4 Status Baseline (Visit 1, W0), W 24 and W 52 The CIBIC+ score used for global functioning assessment. The CIBIC+ assessment comprised of a 7-point rating of severity. 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; The lower score indicated betterment in functioning and higher score means greater dysfunction. The scale was based on interviews with the participant and the caregiver and was completed by an independent rater.
Number of Participants With Abnormal BW at Any Time During Treatment Period Baseline (Visit 1, W0) to W 52 BW of participants were recorded as vital sign at each visit. The BW were identified as of potential clinical concern if the vales were increased or decreased from Baseline by \>=7%. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline in BW was measured as the BW value at specified visit minus the Baseline BW value. Number of participants with abnormal BW at any time during treatment period were reported.
Change From Baseline in Non-fasting Measures of Lipid Metabolism Including Total Cholesterol, High Density Lipoprotein, Low Density Lipoprotein and Triglycerides at Indicated Timepoints. Baseline (Visit 1, W0), W4, W16, W36, W52, W76, and W82 Non-fasting measures of lipid metabolism including cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG) were measured at Baseline (W0), W4, W16, W36, W52, Year 2 W24 and Follow-up. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was calculated as the value at the indicated visit minus the Baseline value.
Number of Participants With Clinical Chemistry Parameters of Potential Clinical Concern Up to 82 weeks The clinical chemistry parameters including alanine amino transferase (ALT), aldolase, aspartate amino transferase (AST), blood urea nitrogen /creatinine (BUN/Creat) ratio, cholesterol (Chol), creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase (GGT), glucose, high density lipid (HDL), low density lipid (LDL), potassium, troponin 1, and urea were assessed as safety parameters. The number of participants with values outside the reference range (potential clinical concern ) at any time on treatment (ATOT) and follow-up period were reported. The treatment period was till W104 followed by 6 weeks of follow-up period till W110 of study.
Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOEe 4 Status Baseline (Visit 1, W0), W24 and W52 The DAD, assessed the ability of a participant 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 participant's 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. The percentage score was calculated as (DAD total score/total number of applicable items) multiplied by 100. The DAD was conducted as an interview with the caregiver and took approximately 20 minutes. Baseline was referred to Visit 1 (W0) assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-Cog) Total Score as a Function of Apolipoprotein E (APOE) 4 Status at W24 and W52 Baseline (Visit 1, W0), W24 and W52 The 11-item ADAS-cog was used to 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. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. Baseline was referred to Visit 1 (W0)assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.
Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE 4 Status at W24 and W52 Baseline (Visit 1, W0), W 24 and W52 The MMSE consisted 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 was completed by the investigator, based on the performance of the participant, and took approximately 5 to 10 minutes to administer. Change from parent Baseline in MMSE was analyzed using a mixed model for repeated measures (MMRM). Baseline was referred to Visit 1 (W0)assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE 4 Status at W24 and W52 Baseline (Visit 1, W0), W24 and W52 The NPI assessed behavioural disturbances comprises 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety and aberrant motor activity. The participant caregiver asked about behaviour in the participant. 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 was calculated by adding all domain scores together: NPI total score (from 0-144) and NPI distress score (from 0-60), with higher scores indicating more severe behavioral disturbance. Baseline was referred to Visit 1 (W0) assessments. Change from Baseline was calculated as value at scheduled time point minus Baseline value.
Change From Baseline in Glycosylated Haemoglobin (HbA1c) Baseline (Vsit 1 W0), W12, W24, W36, W52, W76 and Follow-up (W82) HbA1c was evaluated as safety parameter in this study. The values of change from Baseline was presented. The Baseline assessments were referred to assessments at Visit 1 (W0). Change from Baseline was measured as the BW at specified visit minus the Baseline value.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧West of Scotland Science Park, Glasgow, United Kingdom