Study Of Rosiglitazone XR In Subjects With Mild-to-Moderate Alzheimers
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Rosiglitazone XR
Intervention description: experimental drug
Intervention MeSH terms: Rosiglitazone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 331.0
Sex: All
Minimum age: 51 Years
Maximum age: 91 Years
Healthy volunteers: No
Keywords: open-label extension; tolerability; Alzheimer's disease; Rosiglitazone extended-release (XR); safety; cognition; BRL-049653

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
    

Eligibility 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)