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

NCT00550420 | Terminated Phase 3 Results

• 1 other identifier: AVA102677
• Study Type: interventional
• Target: 331
• Locations: 18 countries
• Sites: 70

Brief 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

Conditions

Alzheimer's Disease

Keywords

open-label extension; tolerability; Alzheimer's disease; Rosiglitazone extended-release (XR); safety; cognition; BRL-049653

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Any Adverse Events (AEs) and Severity of AEs

  AE was defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The drug related-AEs of special interest (AESI) was reported. The severity of the AESI was categorized as mild, moderate and severe. Number of participants with AEs were reported for treatment duration of the study.

  Up to Week 82

Secondary Outcomes (17)

• Number of Participants With Serious AEs and Deaths

  Up to Week 82

• Percentage of Participants With AEs of Edema

  Up to 82 Weeks

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (Visit 1, W0), W4, W8, W12, W16, W24, W36, W52, W64 and Follow-up (W82)

• Change From Baseline in Heart Rate (HR)

  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

  Up to 82 weeks

Study Arms (1)

Arm 1

EXPERIMENTAL

Rosiglitazone XR

Drug: Rosiglitazone XR

Interventions

Rosiglitazone XR DRUG

experimental drug

Arm 1

Eligibility Criteria

• Age: 51 Years - 91 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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 \[seconds\])

You may not qualify if:

• 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 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)

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (70)

GSK Investigational Site

Palo Alto, California, 94305, United States

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GSK Investigational Site

Deerfield Beach, Florida, 33064, United States

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GSK Investigational Site

Hialeah, Florida, 33016, United States

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GSK Investigational Site

Melbourne, Florida, 32901, United States

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GSK Investigational Site

Plantation, Florida, 33317, United States

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GSK Investigational Site

Tampa, Florida, 33613, United States

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GSK Investigational Site

Centerville, Ohio, 45459, United States

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GSK Investigational Site

Tulsa, Oklahoma, 74104, United States

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GSK Investigational Site

Nashville, Tennessee, 37212, United States

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GSK Investigational Site

Graz-Eggenberg, A-8020, Austria

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GSK Investigational Site

Hall in Tirol, A-6060, Austria

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GSK Investigational Site

Plovdiv, 4000, Bulgaria

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GSK Investigational Site

Sofia, 1113, Bulgaria

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GSK Investigational Site

Sofia, 1431, Bulgaria

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GSK Investigational Site

Sofia, 1527, Bulgaria

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GSK Investigational Site

Viña del Mar, Región de Valparaíso, 252-0997, Chile

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GSK Investigational Site

Santiago, Región Metro de Santiago, 7500710, Chile

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GSK Investigational Site

Santiago, Región Metro de Santiago, 7560356, Chile

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GSK Investigational Site

Guangzhou, Guangdong, 510370, China

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GSK Investigational Site

Beijing, 100083, China

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GSK Investigational Site

Beijing, 100730, China

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GSK Investigational Site

Shanghai, 200025, China

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GSK Investigational Site

Shanghai, 200030, China

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GSK Investigational Site

Shanghai, 200040, China

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GSK Investigational Site

Tianjin, 300052, China

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GSK Investigational Site

Zagreb, 10000, Croatia

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GSK Investigational Site

Tallinn, 10138, Estonia

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GSK Investigational Site

Tallinn, 10614, Estonia

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GSK Investigational Site

Tallinn, 10617, Estonia

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GSK Investigational Site

Tartu, 51014, Estonia

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GSK Investigational Site

Ellwangen, Baden-Wurttemberg, 73479, Germany

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GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

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GSK Investigational Site

Günzburg, Bavaria, 89312, Germany

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GSK Investigational Site

Munich, Bavaria, 80331, Germany

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GSK Investigational Site

Nuremberg, Bavaria, 90402, Germany

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GSK Investigational Site

Unterhaching, Bavaria, 82008, Germany

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GSK Investigational Site

Bad Homburg, Hesse, 61348, Germany

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GSK Investigational Site

Achim, Lower Saxony, 28832, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30559, Germany

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GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19053, Germany

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GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, 19055, Germany

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GSK Investigational Site

Baesweiler, North Rhine-Westphalia, 52499, Germany

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GSK Investigational Site

Bochum, North Rhine-Westphalia, 44892, Germany

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GSK Investigational Site

Cologne, North Rhine-Westphalia, 50767, Germany

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GSK Investigational Site

Duisburg, North Rhine-Westphalia, 47051, Germany

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GSK Investigational Site

Jülich, North Rhine-Westphalia, 52428, Germany

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GSK Investigational Site

Dresden, Saxony, 01097, Germany

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GSK Investigational Site

Dresden, Saxony, 01307, Germany

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GSK Investigational Site

Berlin, 12163, Germany

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GSK Investigational Site

Berlin, 12167, Germany

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GSK Investigational Site

Berlin, 13507, Germany

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GSK Investigational Site

Hamburg, 20249, Germany

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GSK Investigational Site

Hamburg, 22083, Germany

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GSK Investigational Site

Athens, 115 21, Greece

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GSK Investigational Site

Thessaloniki, 57010, Greece

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GSK Investigational Site

Pécs, 7623, Hungary

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GSK Investigational Site

Szeged, 6725, Hungary

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GSK Investigational Site

Saltillo, Coahuila, 25000, Mexico

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GSK Investigational Site

Monterrey, Nuevo León, 64660, Mexico

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GSK Investigational Site

México, 14000, Mexico

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GSK Investigational Site

Auckland, 0622, New Zealand

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GSK Investigational Site

Lima, Lima 13, Peru

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GSK Investigational Site

Pasig, 1600, Philippines

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GSK Investigational Site

San Juan, 00918, Puerto Rico

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GSK Investigational Site

Moscow, 115522, Russia

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GSK Investigational Site

Moscow, 117049, Russia

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GSK Investigational Site

Saint Petersburg, 198103, Russia

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GSK Investigational Site

Seongnam-si, 463-707, South Korea

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GSK Investigational Site

Seoul, 143-729, South Korea

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GSK Investigational Site

West of Scotland Science Park, Glasgow, G20 0XA, United Kingdom

Location

Related Publications (1)

• Gold M, Alderton C, Zvartau-Hind M, Egginton S, Saunders AM, Irizarry M, Craft S, Landreth G, Linnamagi 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. Epub 2010 Aug 21.

  PMID: 20733306 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The study was early terminated on 12 February 2009 because RSG XR as monotherapy in Alzheimer's disease failed to demonstrate efficacy.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2007
• First Posted: October 29, 2007
• Study Start: October 1, 2007
• Primary Completion: February 12, 2009
• Study Completion: February 12, 2009
• Last Updated: November 8, 2017
• Results First Posted: November 8, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

PE (1); AU (2); US (9); PR (1); CL (3); RU (3); DE (23); ME (3); CN (7); GB (1); CR (1); NZ (1); GR (2); HU (2); KR (2); BU (4); ES (4); PH (1)