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A 52-week 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).

Conditions
Mild to Moderate Alzheimer's Disease
MedDRA version: 9.1Level: LLTClassification code 10001896Term: Alzheimer's disease
Registration Number
EUCTR2006-005078-28-HU
Lead Sponsor
GlaxoSmithKline Research & Development Ltd
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
686
Inclusion Criteria

Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the RSG XR CIB [GlaxoSmithKline Document Number RM2004/0084/02, 2006], and AVANDIA approved product label.

Subjects eligible for enrollment in the study must meet all of the following criteria:
1. 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.
2. Female subjects able to bear children must agree to use an adequate method of contraception for the duration of the study (See Appendix 11.1 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.1
3. 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).
4. 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 2.
5. Subject has the ability to comply with procedures for cognitive and other testing.
6. Caregiver has provided full written informed consent on his or her own behalf prior
to the performance of any protocol-specified procedure.
7. Subjects considered for enrolment 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) 3.
8. 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.
Where subjects are eligible for inclusion according to additional specified criteria (see Section 11.4; Appendix 4), a further exploratory component of the study will be the investigation of bone health in relation to the administration of RSG XR
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1. 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.
2. 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.
3. 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.
4. 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.
5. Clinically significant peripheral oedema at the time of Visit 1.
6. 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).
7. Subject is an immediate family member or employee of the participating
Investigator, of any of the participating site staff, or of GSK.
8. In France, a subject is neither affiliated with nor a beneficiary of a social security
category.
9. In France, a subject has participated in any study using an investigational drug
during the previous 30 days (except for participation in AVA105640).

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: The primary objective of this study is to evaluate the long-term safety and<br>tolerability of RSG XR in subjects with mild-to-moderate AD who have completed<br>Study AVA105640.;Secondary Objective: The secondary objective of this study is to explore further the long-term efficacy of<br>RSG XR on cognitive function and overall clinical response in subjects with mild-to moderate AD who have completed Study AVA105640.<br>Where subjects are eligible for inclusion according to additional specified criteria, a further exploratory component of the study will be the investigation of bone health in relation to the administration of RSG XR (see Section 11.4; Appendix 4);Primary end point(s): The primary safety endpoint is the incidence and severity of AEs.
Secondary Outcome Measures
NameTimeMethod
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