Last updated: 11/04/2018 05:14:54
Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers
EudraCT ID
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: An open-label extension to study AVA105640, to assess the long-term safety and efficacy of rosiglitazone (extended release tablets) on cognition in subjects with mild to moderate Alzheimer's disease.
Trial description: 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
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:
Number of participants with any adverse events (AEs) and severity of AEs
Timeframe: Up to Week 82
Secondary outcomes:
Number of participants with serious AEs and deaths
Timeframe: Up to Week 82
Percentage of participants with AEs of edema
Timeframe: Up to 82 Weeks
Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82)
Change from Baseline in heart rate (HR)
Timeframe: Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82)
Number of participants with abnormal SBP and DBP at any time during treatment period
Timeframe: Up to 82 weeks
Number of participants with abnormal HR at any time during treatment period
Timeframe: Up to 82 weeks
Change from Baseline in body weight (BW)
Timeframe: Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82)
Number of participants with abnormal BW at any time during treatment period
Timeframe: Baseline (Visit 1, W0) to W 52
Change from Baseline in non-fasting measures of lipid metabolism including total cholesterol, high density lipoprotein, low density lipoprotein and triglycerides at indicated timepoints.
Timeframe: Baseline (Visit 1, W0), W4, W16, W36, W52, W76, and W82
Number of participants with hematological parameters of Potential Clinical Concern
Timeframe: Up to 82 weeks
Number of participants with clinical chemistry parameters of Potential Clinical Concern
Timeframe: Up to 82 weeks
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
Timeframe: Baseline (Visit 1, W0), W24 and W52
Mean Clinician Interview-Based Impression of Change Plus Caregiver input (CIBIC+) score as a function of APOE 4 status
Timeframe: Baseline (Visit 1, W0), W 24 and W 52
Change from Baseline in Mini Mental State Examination (MMSE) total score as a function of APOE 4 status at W24 and W52
Timeframe: Baseline (Visit 1, W0), W 24 and W52
Change from Baseline in Disability Assessment for Dementia scale (DAD) total score as a function of APOEe 4 status
Timeframe: Baseline (Visit 1, W0), W24 and W52
Change from Baseline in Neuropsychiatric Inventory (NPI) total score as a function of APOE 4 status at W24 and W52
Timeframe: Baseline (Visit 1, W0), W24 and W52
Change from Baseline in glycosylated haemoglobin (HbA1c)
Timeframe: Baseline (Vsit 1 W0), W12, W24, W36, W52, W76 and Follow-up (W82)
Interventions:
Enrollment:
331
Primary completion date:
2009-12-02
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Michael Gold, Claire Alderton, Marina Zvartau-Hind, Sally Egginton, Ann M Saunders, Michael Irizarry, Suzanne Craft, Gary Landreth, Ülla Linnamägi, Sharon Sawchak. Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer's Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study. Dement Geriatr Cogn Disord. 2010;30(2):131-46.
Medical condition
Alzheimer's Disease
Product
rosiglitazone
Collaborators
Not applicable
Study date(s)
October 2007 to February 2009
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
51 - 91 years
Accepts healthy volunteers
No
- Male or female subject who has successfully completed Visit 8 of AVA105640 without safety/tolerability issues, where in the opinion of the subject /carer and of the investigator, it would be beneficial to receive RSG XR
- Female subjects able to bear children must agree to use an adequate method of contraception for the duration of the study for details of highly effective methods to avoid pregnancy). Female subjects who are pre-menopausal or who have been post-menopausal for <1 year must undertake pregnancy testing (urine test) £7 days before Visit 1, which must be negative
- Subject had a serious adverse experience or clinically significant laboratory abnormality during AVA105640, which in the opinion of the investigator could have been attributable to study medication, and which is ongoing at Visit 1
- The subject is felt by the investigator to be unsuitable (on the basis of health, compliance, caregiver availability, or for any other reason) for inclusion in the study
Inclusion and exclusion criteria
Inclusion criteria:
- Male or female subject who has successfully completed Visit 8 of AVA105640 without safety/tolerability issues, where in the opinion of the subject /carer and of the investigator, it would be beneficial to receive RSG XR
- Female subjects able to bear children must agree to use an adequate method of contraception for the duration of the study for details of highly effective methods to avoid pregnancy). Female subjects who are pre-menopausal or who have been post-menopausal for <1 year must undertake pregnancy testing (urine test) £7 days before Visit 1, which must be negative
- Subject is willing to participate in the extension study and has provided full written informed consent prior to the performance of any protocol-specified procedure; or if unable to provide informed consent due to cognitive status, full written informed consent on behalf of the subject has been provided by a legally acceptable representative (where this is in accordance with local laws, regulations and ethics committee policy)
- Subject lives with (or has substantial periods of contact with) a regular caregiver who is willing to attend all visits, oversee the subject's compliance with protocol-specified procedures and study medication, and report on subject's status
- Subject has the ability to comply with procedures for cognitive and other testing
- Caregiver has provided full written informed consent on his or her own behalf prior to the performance of any protocol-specified procedure
- Subjects considered for enrollment must have a QTc (either QTc B (Bazett's correction) or QTc F (Fridericia's correction)) <450msec at Visit 1, with the exception of subjects with bundle branch block (for whom either QTc B or QTc F must be <480msec)
- In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
- Post-menopause [Becker, 2001]: Menopause is the age associated with complete cessation of menstrual cycles, menses, and implies the loss of reproductive potential by ovarian failure. This typically occurs around age 50, although it may occur earlier. A practical definition accepts menopause after one year without menses with an appropriate clinical profile, e.g., age appropriate, >45 years, in the absence of hormone replacement therapy. In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory (these levels are suggested guidelines and may need to be adjusted for specific laboratories/assays
- Females, who are on hormone replacement therapy (HRT), and whose menopausal status is in doubt, will be required to use a highly effective method to avoid pregnancy, as outlined in the protocol, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post‑menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw as detailed in the preceding paragraph; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a highly effective method to avoid pregnancy
- A non-cohabiting caregiver must spend sufficient time with the subject so that, in the opinion of the Investigator, the caregiver can reliably assess cognitive function, activities and behaviour, and report on the subject's compliance and health. As caregiver time spent with a potential subject is anticipated to be highly variable across countries and cultures, GSK will consider a variety of different measures by which this stipulation may be met, and GSK should be consulted if adequacy of a caregiver situation is in doubt. However, as guidance, the ability for a caregiver to meet his/her expected responsibilities for this study would normally be possible when the caregiver spends no less than 10 hours per week with the subject, divided over multiple days
- For the purposes of these criteria, QTc B is defined as (QT interval [msec]) / (square root of RR interval [seconds]); and QTc F is defined as (QT interval [msec]) / (cube root of RR interval [seconds])
Exclusion criteria:
- Subject had a serious adverse experience or clinically significant laboratory abnormality during AVA105640, which in the opinion of the investigator could have been attributable to study medication, and which is ongoing at Visit 1
- The subject is felt by the investigator to be unsuitable (on the basis of health, compliance, caregiver availability, or for any other reason) for inclusion in the study
- The subject experienced a significant cardiovascular event during AVA105640 (e.g. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome [non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina] or significant arrhythmia), unless a thorough cardiovascular evaluation has been performed which confirms that the subject does not have congestive heart failure, and is clinically stable
- Clinical/investigational evidence of congestive heart failure defined by the New York Heart Association (NYHA) criteria (Class I to IV cardiac status) at the time of Visit 1
- Clinically significant peripheral oedema at the time of Visit 1
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase values >2.5 times the upper limit of normal (ULN), total bilirubin values >1.5 times the ULN, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C)
- Subject is an immediate family member or employee of the participating Investigator, of any of the participating site staff, or of GSK
- In France, a subject is neither affiliated with nor a beneficiary of a social security category
- In France, a subject has participated in any study using an investigational drug during the previous 30 days (except for participation in AVA105640)
Trial location(s)
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
Status
Study Complete
Location
GSK Investigational Site
Santiago, Región Metro De Santiago, Chile, 7560356
Status
Study Complete
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19053
Status
Study Complete
Location
GSK Investigational Site
Baesweiler, Nordrhein-Westfalen, Germany, 52499
Status
Study Complete
Location
GSK Investigational Site
Centerville, Ohio, United States, 45459
Status
Study Complete
Location
GSK Investigational Site
Deerfield Beach, Florida, United States, 33064
Status
Study Complete
Location
GSK Investigational Site
West of Scotland Science Park, Glasgow, United Kingdom, G20 0XA
Status
Study Complete
Location
GSK Investigational Site
Viña del Mar, Valparaíso, Chile, 252-0997
Status
Study Complete
Location
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
Status
Study Complete
Location
GSK Investigational Site
Juelich, Nordrhein-Westfalen, Germany, 52428
Status
Study Complete
Location
GSK Investigational Site
Plantation, Florida, United States, 33317
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Guenzburg, Bayern, Germany, 89312
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Duisburg, Nordrhein-Westfalen, Germany, 47051
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ellwangen, Baden-Wuerttemberg, Germany, 73479
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hialeah, Florida, United States, 33016
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37212
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30559
Status
Study Complete
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44892
Status
Study Complete
Location
GSK Investigational Site
San Juan, Puerto Rico, Puerto Rico, 00918
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50767
Status
Study Complete
Location
GSK Investigational Site
Melbourne, Florida, United States, 32901
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Palo Alto, California, United States, 94305
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2009-12-02
Actual study completion date
2009-12-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Participate in clinical trial
Additional information
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereAccess to clinical trial data by researchers
Visit website