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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: October 26, 2016
Last verified: October 2016

October 25, 2007
October 26, 2016
October 2007
February 2009   (final data collection date for primary outcome measure)
Number of participants with any adverse events (AEs) and severity of adverse events [ Time Frame: Up to 110 weeks ] [ Designated as safety issue: No ]
An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The severity of the AEs was categorized as mild, moderate and severe. Number of participants with any AEs and as per severity were reported. The baseline assessments were referred to assessments at Visit 1 Week (W) 0.
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
  • Number of deaths and number of participants with serious adverse events (SAEs) [ Time Frame: Up to 110 weeks ] [ Designated as safety issue: No ]
    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 baseline assessments were referred to assessments at Visit 1 (W0).
  • Percentage of participants with AEs of edema [ Time Frame: Up to 110 Weeks ] [ Designated as safety issue: No ]
    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. Edema peripheral, face edema, and eyelid edema were observed and percentage of participants with edema were reported. The baseline assessments were referred to assessments at Visit 1 (W0).
  • Number of participants with abnormal systolic Blood pressure (SBP) and diastolic blood pressure (DBP) at any time during treatment period [ Time Frame: Up to 104 weeks ] [ Designated as safety issue: No ]
    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 systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Baseline (Visit 1) to 110 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline (Visit 1, W0) to Week 110 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 104 weeks ] [ Designated as safety issue: No ]
    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.
  • Change from baseline in body weight (BW) [ Time Frame: Baseline (Visit 1, W0) to W 104 ] [ Designated as safety issue: No ]
    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 BW at any time during treatment period [ Time Frame: Baseline (Visit 1, W0) to W 52 ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline (Visit 1, W0) to W 110 ] [ Designated as safety issue: No ]
    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 hematological parameters of Potential Clinical Concern [ Time Frame: Up to 110 weeks ] [ Designated as safety issue: No ]
    The hematological parameters including eosinophils, lymphocytes, monocytes, platelet count, Segmented Neutrophils (Seg neutro), 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.
  • Number of participants with clinical chemistry parameters of Potential Clinical Concern [ Time Frame: Up to 110 weeks ] [ Designated as safety issue: No ]
    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 Alzheimer's Disease Assessment Scale - cognitive (ADAS-Cog) total score as a function of Apolipoprotein E (APOE) 4 status at W24 and W52 [ Time Frame: Baseline, W24 and W52 ] [ Designated as safety issue: No ]
    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 the baseline assessment of the parent study, (AVA105640). Change from Baseline was calculated as value at scheduled time point minus Baseline value.
  • Change from baseline in Clinician Interview-Based Impression of Change Plus Caregiver input (CIBIC+) score as a function of APOE 4 status [ Time Frame: Baseline, W 24 and W 52 ] [ Designated as safety issue: No ]
    he CIBIC+ global functioning assessment comprised of a 7-point rating of severity (assessed at baseline) and change (assessed at subsequent time points). The scale was based on interviews with the subject and the caregiver and was completed by an independent rater. Baseline was referred to the baseline assessment of the parent study, (AVA105640). The W48 and W76 of the study AVA105640 were referred as W24 and W52 of the study AVA102677. 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 [ Time Frame: Baseline, W 24 and W52 ] [ Designated as safety issue: No ]
    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 subject, 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 the baseline assessment of the parent study, (AVA105640). The W48 and W76 of the study AVA105640 were referred as W24 and W52 of the study AVA102677. Change from Baseline was calculated as value at scheduled time point minus Baseline value.
  • Change from baseline in Disability Assessment for Dementia scale (DAD) total score as a function of APOEe 4 status [ Time Frame: Baseline, W24 and W52 ] [ Designated as safety issue: No ]
    The DAD scale assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale included 23 items relating to instrumental ADL and 17 items relating to basic self-care. The DAD was conducted as an interview with the caregiver and took approximately 20 minutes. Baseline was referred to the baseline assessment of the parent study, (AVA105640). The W48 and W76 of the study AVA105640 were referred as W24 and W52 of the study AVA102677. 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 [ Time Frame: Baseline, W24 and W52 ] [ Designated as safety issue: No ]
    The NPI was an assessment of the frequency and severity of behavioural disturbances in dementia. The inventory was comprised of 10 dimensions: delusions, hallucinations, dysphoria, apathy, euphoria, disinhibition, aggressiveness and agitation, irritability, anxiety, aberrant motor activity. Each dimension had a screening question with between 7 and 9 follow-up questions relating to symptoms, asked if the answer to the screening question was yes. Change from parent baseline in NPI total score was analyzed using a mixed model for repeated measures (MMRM). Baseline was referred to the baseline assessment of the parent study, (AVA105640). The W48 and W76 of the study AVA105640 were referred as W24 and W52 of the study AVA102677. Change from Baseline was calculated as value at scheduled time point minus Baseline value.
  • Change from baseline in glycosylated haemoglobin (HbA1c) [ Time Frame: Baseline (Vsiti 1 W0) to W110 ] [ Designated as safety issue: No ]
    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.
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. doi: 10.1159/000318845.

*   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   (Adult, Senior)
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
India,   Pakistan
 
NCT00550420
AVA102677
Not Provided
Yes
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
October 2016

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