Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers

This study has been terminated.
(Based on preliminary parent study results)
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00550420
First received: October 25, 2007
Last updated: November 21, 2013
Last verified: November 2013

October 25, 2007
November 21, 2013
October 2007
February 2009   (final data collection date for primary outcome measure)
Incidence and severity of Adverse Events. [ Time Frame: 52 weeks ]
Incidence and severity of Adverse Events over the course of 52 weeks. [ Time Frame: 52 Weeks ]
Complete list of historical versions of study NCT00550420 on ClinicalTrials.gov Archive Site
ADAS-cog, CIBIC+, MMSE, DAD and NPI total scores as a function of APOE e4 status. Incidence and severity of SAEs, percentage of subjects with edema, change from baseline in vital signs, weight, non-fasting measures of lipid metabolism. [ Time Frame: 52 weeks ]
ADAS-cog, CIBIC+, MMSE, DAD and NPI total scores as a function of APOE e4 status. Incidence and severity(52 weeks) of SAEs, percentage of subjects with edema, change from baseline in vital signs, weight, non-fasting measures of lipid metabolism. [ Time Frame: 52 Weeks ]
Not Provided
Not Provided
 
Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers
An Open-label Extension Study of the Long-term Safety and Efficacy of Rosiglitazone Extended-release (RSG XR) in Subjects With Mild-to-moderate Alzheimer's Disease (REFLECT-5)

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

Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Alzheimer's Disease
Drug: Rosiglitazone XR
experimental drug
Experimental: Arm 1
Rosiglitazone XR
Intervention: Drug: Rosiglitazone XR
Gold M, Alderton C, Zvartau-Hind M, Egginton S, Saunders AM, Irizarry M, Craft S, Landreth G, Linnamägi U, Sawchak S. Rosiglitazone monotherapy in mild-to-moderate alzheimer's disease: results from a randomized, double-blind, placebo-controlled phase III study. Dement Geriatr Cogn Disord. 2010;30(2):131-46. Epub 2010 Aug 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
383
February 2009
February 2009   (final data collection date for primary outcome measure)

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)
Both
51 Years to 91 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Austria,   Bulgaria,   Chile,   China,   Croatia,   Estonia,   Germany,   Greece,   Hungary,   Korea, Republic of,   Mexico,   New Zealand,   Peru,   Philippines,   Puerto Rico,   Russian Federation,   United Kingdom
 
NCT00550420
AVA102677
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP