AzTrials
AzTrials

Alzheimer's DiseaseREFLECT-2NCT00348309

Rosiglitazone (Extended Release Tablets) As Adjunctive Therapy For Subjects With Mild To Moderate Alzheimer's Disease

A study testing Rosiglitazone Extended Release 2mg, Rosiglitazone Extended Release 8mg and Donepezil in people with Alzheimer's Disease, run by GlaxoSmithKline at 249 sites in 19 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG. Read more about this study

Who is it for?
Ages 50 to 90 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
Rosiglitazone Extended Release 2mg, Rosiglitazone Extended Release 8mg and Donepezil
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,496 participants
Where
249 sitesin 19 countries
Study dates
6 Jul 2006to 28 Jan 2009
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A subject will be eligible for inclusion in this study only if all of the following criteria apply:
  • Male or female subject with a clinical diagnosis of probable Alzheimer's disease in accordance with NINCDS-ADRDA criteria.
  • (Note: National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and Alzheimer's Disease and Related Disorders Association (ADRDA).)
  • Subject has mild to moderate Alzheimer's disease as defined by a MMSE score 10 to 26 inclusive at Screening.
  • Hachinski Ischemia Score ≤ 4 at Screening.
  • Age ≥50 and ≤90 years.
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  • At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).
  • Current use of medication is in accordance with the criteria listed in Table 2 (Permitted Medications,).
  • Female subjects must be post-menopausal (i.e. >1 year without menstrual period), surgically sterile, or agree to use adequate method of contraception for the duration of the study. Female subjects who are pre-menopausal or who have been post-menopausal for <1 year must undertake pregnancy testing (urine test) at Visit 1, which must be negative.
  • Brain CT or MRI scan performed within the past 12 months or at Screening, showing no evidence of any other potential cause of dementia other than Alzheimer's disease.
  • (Note: Questionable CT or MRI scans should be discussed with the medical monitor, using central imaging guidelines.)
  • Neurological exam without focal changes (excluding changes attributable to AD or peripheral trauma).
  • Subject has the ability to comply with procedures for cognitive and other testing.
  • 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.
  • Note: 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 behavior, 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.)
  • Subject 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.
  • (Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations and ethics committee policy.)
  • Caregiver has provided full written informed consent on his/her own behalf prior to the performance of any protocol-specified procedure.
  • 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).
  • (Note: 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]).)

Who cannot join

  • A subject will not be eligible for inclusion in this study if any of the following criteria apply:
  • Diagnosis of possible, probable, or definite vascular dementia in accordance with NINDS-AIREN criteria.
  • (Note: National Institute of Neurological Disorders and Stroke (NINDS) and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN).)
  • History or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease (stroke, hemorrhage), structural abnormality, epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease.
  • Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology, or active thyroid dysfunction (particularly that suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH) that are clinically significant in the opinion of the investigator.
  • (Note: Testing is required for each parameter only when no result is available from previous 12 months.)
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  • History of Type 1 diabetes mellitus or secondary diabetes mellitus.
  • Type 2 diabetes mellitus where the subject is being treated with insulin, a PPARγ agonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide).
  • Any patient with an HbA1c ≥8.5%. (See Section 6.3.7.4 for Safety Measures for Enrolled Subjects with Type 2 Diabetes Mellitus.)
  • History or clinical/investigational evidence of congestive heart failure defined by the New York Heart Association criteria (Class I to IV cardiac status;).
  • History of cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome [non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina] or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled).
  • History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study, major depressive disorder (according to DSM-IV) in the past year, or current active depression requiring initiation of treatment.
  • (Note: If not currently treated, but active depression is suspected, the Cornell Scale for Depression in Dementia (CSDD) can be used by the Investigator as a guide for deciding whether a prospective subject requires treatment. If the subject has a CSDD score >7, the Investigator should decide if the subject has depression in need of prescribed medication, and a CSDD >12 is considered a strong indicator that treatment is needed. Subjects will be allowed to re-screen after their depression has been adequately managed for >3 months.)
  • History or presence of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, medical or psychiatric condition, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study.
  • Clinically significant peripheral edema at the time of screening.
  • Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria for substance-related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia.
  • Systolic blood pressure >165 or <90 mmHg or diastolic blood pressure >95 or <60 mmHg at the time of screening.
  • Clinically significant anemia (i.e. hemoglobin <11 g/dL for males or <10 g/dL for females) or presence of hemoglobinopathies which would prevent accurate assessment of HbA1c.
  • Abnormal kidney function tests (>1.5 the upper limit of normal (ULN)).
  • ALT, AST, or alkaline phosphatase values >2.5 times the 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).
  • (Note: For subjects with a diagnosis of Gilberts Syndrome and an isolated increase in total bilirubin >1.5 ULN, fractionation should be performed. If all of the following conditions are met, the patient may enter or remain in the study, even if total bilirubin >1.5 ULN:
  • an elevated unconjugated (indirect) bilirubin;
  • the percentage of direct bilirubin <35%;
  • ALT, AST, and alkaline phosphatase <2.5 ULN if subject is in screening (<2.0 ULN for Canadian subjects only), or ≤3 ULN if subject is already randomized into the study)
  • History of a bone marrow transplant.
  • Subject is unable (with assistance, if appropriate) to take study medication as prescribed throughout the study or is at risk of non-compliance with study medication or procedures.
  • 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.
  • The French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).
  • Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision are prohibited for 6 months prior to Screening, as well as for the duration of the study.

Trial locations and contacts

249 sites in 19 countries.

249 sites in 19 countries

Germany47 sites

  • GSK Investigational Site

    Achim, Lower Saxony, 28832

  • GSK Investigational Site

    Bad Honnef, North Rhine-Westphalia, 53604

  • GSK Investigational Site

    Baesweiler, North Rhine-Westphalia, 52499

  • GSK Investigational Site

    Bergisch Gladbach, North Rhine-Westphalia, 51465

  • GSK Investigational Site

    Böblingen, Baden-Wurttemberg, 71034

  • GSK Investigational Site

    Bochum, North Rhine-Westphalia, 44791

  • GSK Investigational Site

    Bochum, North Rhine-Westphalia, 44805

  • GSK Investigational Site

    Bochum, North Rhine-Westphalia, 44809

  • GSK Investigational Site

    Bochum, North Rhine-Westphalia, 44869

  • GSK Investigational Site

    Bochum, North Rhine-Westphalia, 44892

  • GSK Investigational Site

    Bockhorn, Lower Saxony, 26345

  • GSK Investigational Site

    Cologne, North Rhine-Westphalia, 50767

  • GSK Investigational Site

    Cologne, North Rhine-Westphalia, 51069

  • GSK Investigational Site

    Duisburg, North Rhine-Westphalia, 47051

  • GSK Investigational Site

    Düren, North Rhine-Westphalia, 52349

  • GSK Investigational Site

    Essen, North Rhine-Westphalia, 45138

  • GSK Investigational Site

    Ganderkesee, Lower Saxony, 27777

  • GSK Investigational Site

    Göttingen, Lower Saxony, 37075

  • GSK Investigational Site

    Hamburg, 20249

  • GSK Investigational Site

    Hamburg, 21149

  • GSK Investigational Site

    Hamburg, 22083

  • GSK Investigational Site

    Hamburg, 22143

  • GSK Investigational Site

    Hanover, Lower Saxony, 30559

  • GSK Investigational Site

    Hattingen, North Rhine-Westphalia, 45525

  • GSK Investigational Site

    Hildesheim, Lower Saxony, 31134

  • GSK Investigational Site

    Hüttenberg, Hesse, 35625

  • GSK Investigational Site

    Jülich, North Rhine-Westphalia, 52428

  • GSK Investigational Site

    Krefeld, North Rhine-Westphalia, 47800

  • GSK Investigational Site

    Lüneburg, Lower Saxony, 21335

  • GSK Investigational Site

    Munich, Bavaria, 80331

  • GSK Investigational Site

    Munich, Bavaria, 80333

  • GSK Investigational Site

    Munich, Bavaria, 80336

  • GSK Investigational Site

    Munich, Bavaria, 81377

  • GSK Investigational Site

    Munich, Bavaria, 81667

  • GSK Investigational Site

    Neuburg an der Donau, Bavaria, 86633

  • GSK Investigational Site

    Nuremberg, Bavaria, 90402

  • GSK Investigational Site

    Nuremberg, Bavaria, 90403

  • GSK Investigational Site

    Ostfildern, Baden-Wurttemberg, 73760

  • GSK Investigational Site

    Regensburg, Bavaria, 93053

  • GSK Investigational Site

    Remscheid, North Rhine-Westphalia, 42853

  • GSK Investigational Site

    Schwerin, Mecklenburg-Vorpommern, 19053

  • GSK Investigational Site

    Schwerin, Mecklenburg-Vorpommern, 19055

  • GSK Investigational Site

    Siegen, North Rhine-Westphalia, 57072

  • GSK Investigational Site

    Stuttgart, Baden-Wurttemberg, 70178

  • GSK Investigational Site

    Ulm, Baden-Wurttemberg, 89073

  • GSK Investigational Site

    Westerstede, Lower Saxony, 26655

  • GSK Investigational Site

    Würzburg, Bavaria, 97070

Other trials in Germany

United States41 sites

  • GSK Investigational Site

    Albany, New York, 12205

  • GSK Investigational Site

    Austin, Texas, 78757

  • GSK Investigational Site

    Baltimore, Maryland, 21224

  • GSK Investigational Site

    Bennington, Vermont, 05201

  • GSK Investigational Site

    Brooklyn, New York, 11235

  • GSK Investigational Site

    Delray Beach, Florida, 33445

  • GSK Investigational Site

    Denver, Colorado, 80212

  • GSK Investigational Site

    Durham, North Carolina, 27705

  • GSK Investigational Site

    Fort Wayne, Indiana, 46805

  • GSK Investigational Site

    Fresno, California, 93720

  • GSK Investigational Site

    Glen Burnie, Maryland, 21061

  • GSK Investigational Site

    Hallandale, Florida, 33009

  • GSK Investigational Site

    Hoffman Estates, Illinois, 60194

  • GSK Investigational Site

    Houston, Texas, 77030

  • GSK Investigational Site

    Indianapolis, Indiana, 46202

  • GSK Investigational Site

    Lebanon, New Hampshire, 03756

  • GSK Investigational Site

    Litchfield Park, Arizona, 85340

  • GSK Investigational Site

    Little Rock, Arkansas, 72205

  • GSK Investigational Site

    Miami, Florida, 33143

  • GSK Investigational Site

    Morristown, New Jersey, 07960

  • GSK Investigational Site

    Nashville, Tennessee, 37203

  • GSK Investigational Site

    New Haven, Connecticut, 06510

  • GSK Investigational Site

    New York, New York, 10021

  • GSK Investigational Site

    Nutley, New Jersey, 07110

  • GSK Investigational Site

    Phoenix, Arizona, 85004

  • GSK Investigational Site

    Phoenix, Arizona, 85006

  • GSK Investigational Site

    Phoenix, Arizona, 85050

  • GSK Investigational Site

    Portland, Oregon, 97239

  • GSK Investigational Site

    Princeton, New Jersey, 08540

  • GSK Investigational Site

    Providence, Rhode Island, 02906

  • GSK Investigational Site

    Raleigh, North Carolina, 27607

  • GSK Investigational Site

    Rancho Mirage, California, 92270

  • GSK Investigational Site

    Rockville, Maryland, 20852

  • GSK Investigational Site

    Sacramento, California, 95816

  • GSK Investigational Site

    Saint Paul, Minnesota, 55101

  • GSK Investigational Site

    Sarasota, Florida, 34233

  • GSK Investigational Site

    Sherman Oaks, California, 91403

  • GSK Investigational Site

    South Ogden, Utah, 84403

  • GSK Investigational Site

    St. Petersburg, Florida, 33701

  • GSK Investigational Site

    Stratford, New Jersey, 08084

  • GSK Investigational Site

    West Palm Beach, Florida, 33407

Other trials in United States

France34 sites

  • GSK Investigational Site

    Angoulême, 16000

  • GSK Investigational Site

    Arcachon, 33120

  • GSK Investigational Site

    Avignon, 84000

  • GSK Investigational Site

    Bourg-en-Bresse, 01012

  • GSK Investigational Site

    Caen, 14033

  • GSK Investigational Site

    Dijon, 21000

  • GSK Investigational Site

    Issy-les-Moulineaux, 92130

  • GSK Investigational Site

    Ivry, 94206

  • GSK Investigational Site

    Luynes, 37230

  • GSK Investigational Site

    Lyon, 69006

  • GSK Investigational Site

    Marseille, 13008

  • GSK Investigational Site

    Marseille, 13009

  • GSK Investigational Site

    Metz, 57038

  • GSK Investigational Site

    Montpellier, 34080

  • GSK Investigational Site

    Nantes, 44000

  • GSK Investigational Site

    Nantes, 44093

  • GSK Investigational Site

    Nantes, 44200

  • GSK Investigational Site

    Nice, 06002

  • GSK Investigational Site

    Paris, 75012

  • GSK Investigational Site

    Paris, 75013

  • GSK Investigational Site

    Paris, 75018

  • GSK Investigational Site

    Pau, 64000

  • GSK Investigational Site

    Pessac, 33604

  • GSK Investigational Site

    Reims, 51100

  • GSK Investigational Site

    Rennes, 35000

  • GSK Investigational Site

    Rodez, 12000

  • GSK Investigational Site

    Saint-Etienne, 42100

  • GSK Investigational Site

    Saint-Jean-de-Luz, 64500

  • GSK Investigational Site

    Saint-Nicolas-de-Port, 54210

  • GSK Investigational Site

    Saint-Ouen-la-Rouërie, 35460

  • GSK Investigational Site

    Tinténiac, 35190

  • GSK Investigational Site

    Tours, 37100

  • GSK Investigational Site

    Verny, 57420

  • GSK Investigational Site

    Vichy, 03200

Other trials in France

Japan20 sites

  • GSK Investigational Site

    Aichi, 451-0052

  • GSK Investigational Site

    Aichi, 455-8530

  • GSK Investigational Site

    Fukuoka, 813-8588

  • GSK Investigational Site

    Fukuoka, 819-0165

  • GSK Investigational Site

    Gunma, 375-0017

  • GSK Investigational Site

    Hiroshima, 733-0864

  • GSK Investigational Site

    Hokkaido, 005-0853

  • GSK Investigational Site

    Hokkaido, 080-2470

  • GSK Investigational Site

    Hyōgo, 672-8043

  • GSK Investigational Site

    Ibaraki, 300-0053

  • GSK Investigational Site

    Kagawa, 761-8024

  • GSK Investigational Site

    Kanagawa, 231-0023

  • GSK Investigational Site

    Kanagawa, 238-0042

  • GSK Investigational Site

    Kochi, 780-0842

  • GSK Investigational Site

    Kumamoto, 861-8002

  • GSK Investigational Site

    Kyoto, 607-8062

  • GSK Investigational Site

    Nagano, 399-8695

  • GSK Investigational Site

    Osaka, 567-0011

  • GSK Investigational Site

    Osaka, 569-1041

  • GSK Investigational Site

    Tokyo, 193-0998

Other trials in Japan

Italy19 sites

  • GSK Investigational Site

    Ancona, The Marches, 60020

  • GSK Investigational Site

    Arezzo, Tuscany, 52100

  • GSK Investigational Site

    Bari, Apulia, 70124

  • GSK Investigational Site

    Bologna, Emilia-Romagna, 40138

  • GSK Investigational Site

    Brescia, Lombardy, 25123

  • GSK Investigational Site

    Brescia, Lombardy, 25125

  • GSK Investigational Site

    Chieti Scalo, Abruzzo, 66013

  • GSK Investigational Site

    Florence, Tuscany, 50134

  • GSK Investigational Site

    Milan, Lombardy, 20122

  • GSK Investigational Site

    Milan, Lombardy, 20127

  • GSK Investigational Site

    Naples, Campania, 80131

  • GSK Investigational Site

    Pavia, Lombardy, 27100

  • GSK Investigational Site

    Pisa, Tuscany, 56126

  • GSK Investigational Site

    Rho, Lombardy, 20017

  • GSK Investigational Site

    Rome, Lazio, 00148

  • GSK Investigational Site

    Rome, Lazio, 00163

  • GSK Investigational Site

    Rome, Lazio, 00186

  • GSK Investigational Site

    San Felice A Cancello Caserta, Campania, 81027

  • GSK Investigational Site

    Verona, Veneto, 37100

Other trials in Italy

Canada17 sites

  • GSK Investigational Site

    Barrie, Ontario, L4M 4S5

  • GSK Investigational Site

    Calgary, Alberta, T2N 4N1

  • GSK Investigational Site

    Charlottetown, Prince Edward Island, C1A 5Y8

  • GSK Investigational Site

    Greenfield Park, Quebec, J4V 2J2

  • GSK Investigational Site

    Kingston, Ontario, K7L 4X3

  • GSK Investigational Site

    Medicine Hat, Alberta, T1A 4C2

  • GSK Investigational Site

    Moncton, New Brunswick, E1C 4B7

  • GSK Investigational Site

    Montreal, Quebec, H1T 2M4

  • GSK Investigational Site

    Montreal, Quebec, H4H 1R3

  • GSK Investigational Site

    Peterborough, Ontario, K9H 2P4

  • GSK Investigational Site

    Québec, G1R 3X5

  • GSK Investigational Site

    Regina, Saskatchewan, S4T 1A5

  • GSK Investigational Site

    Sherbrooke, Quebec, J1H 1Z1

  • GSK Investigational Site

    Toronto, Ontario, M5T 2S8

  • GSK Investigational Site

    Toronto, Ontario, M6M 3Z5

  • GSK Investigational Site

    Victoria, British Columbia, V8T 5G1

  • GSK Investigational Site

    Whitby, Ontario, L1N 5S9

Other trials in Canada

Spain15 sites

  • GSK Investigational Site

    A Coruña, 15006

  • GSK Investigational Site

    Burgos, 09006

  • GSK Investigational Site

    Castellon, 12004

  • GSK Investigational Site

    Elche (Alicante), 03202

  • GSK Investigational Site

    Galdakano, 48960

  • GSK Investigational Site

    Girona, 17190

  • GSK Investigational Site

    Granada, 18013

  • GSK Investigational Site

    Madrid, 28006

  • GSK Investigational Site

    Madrid, 28040

  • GSK Investigational Site

    Madrid, 28046

  • GSK Investigational Site

    Málaga, 29071

  • GSK Investigational Site

    Murcia, 30120

  • GSK Investigational Site

    Pamplona, 31008

  • GSK Investigational Site

    San Sebastián, 20014

  • GSK Investigational Site

    Valencia, 46010

Other trials in Spain

Argentina9 sites

  • GSK Investigational Site

    Buenos Aires, C1425CDC

  • GSK Investigational Site

    Ciudad Autónoma de Buenos Aires, Buenos Aires, C1192AAW

  • GSK Investigational Site

    Ciudad Autónoma de Buenos Aires, Buenos Aires, C1419HDN

  • GSK Investigational Site

    Ciudad de Buenos Aires, Buenos Aires, C1431FWO

  • GSK Investigational Site

    Córdoba, Córdoba Province, 5000

  • GSK Investigational Site

    Córdoba, Córdoba Province, X5004AOA

  • GSK Investigational Site

    Córdoba, Córdoba Province, x5009bin

  • GSK Investigational Site

    Godoy Cruz, Mendoza Province, M5504FMI

  • GSK Investigational Site

    Mendoza, CPM5500HIF

Other trials in Argentina

India8 sites

  • GSK Investigational Site

    Bangalore, 560 054

  • GSK Investigational Site

    Bangalore, 560034

  • GSK Investigational Site

    Hyderabad, 500 034

  • GSK Investigational Site

    Mumbai, 400010

  • GSK Investigational Site

    Nagpur, 440010

  • GSK Investigational Site

    New Delhi, 110002

  • GSK Investigational Site

    Pune, 411004

  • GSK Investigational Site

    Varanasi, 221005

Other trials in India

Poland7 sites

  • GSK Investigational Site

    Bydgoszcz, 85-096

  • GSK Investigational Site

    Katowice, 40-752

  • GSK Investigational Site

    Lodz, 91-348

  • GSK Investigational Site

    Mosina, 62-050

  • GSK Investigational Site

    Poznan, 61-298

  • GSK Investigational Site

    Sopot, 81-824

  • GSK Investigational Site

    Warsaw, 02-507

Other trials in Poland

Austria6 sites

  • GSK Investigational Site

    Hall in Tirol, A-6060

  • GSK Investigational Site

    Innsbruck, A-6020

  • GSK Investigational Site

    Vienna, 1010

  • GSK Investigational Site

    Vienna, 1030

  • GSK Investigational Site

    Vienna, A-1130

  • GSK Investigational Site

    Vienna, A-1220

Other trials in Austria

Czechia5 sites

  • GSK Investigational Site

    Ostrava, 702 00

  • GSK Investigational Site

    Prague, 10000

  • GSK Investigational Site

    Prague, 120 00

  • GSK Investigational Site

    Prague, 150 18

  • GSK Investigational Site

    Prague, 170 00

Other trials in Czechia

Chile4 sites

  • GSK Investigational Site

    Providencia / Santiago, Región Metro de Santiago, 7500710

  • GSK Investigational Site

    Puente Alto - Santiago, Región Metro de Santiago, 8207257

  • GSK Investigational Site

    Santiago, Región Metro de Santiago, 7560356

  • GSK Investigational Site

    Viña del Mar, Valparaiso, 252-0997

Other trials in Chile

Greece4 sites

  • GSK Investigational Site

    Athens, 115 21

  • GSK Investigational Site

    Athens, 151 23

  • GSK Investigational Site

    Melíssia, 151 27

  • GSK Investigational Site

    Thessaloniki, 57010

Other trials in Greece

Mexico4 sites

  • GSK Investigational Site

    México, 14000

  • GSK Investigational Site

    Monterrey, Nuevo León, 64660

  • GSK Investigational Site

    Monterrey, Nuevo León, 64710

  • GSK Investigational Site

    Saltillo, Coahuila, 25000

Other trials in Mexico

Brazil3 sites

  • GSK Investigational Site

    Belo Horizonte, 30130-110

  • GSK Investigational Site

    Ribeirão Preto, 14048-900

  • GSK Investigational Site

    São Paulo, 040023-900

Other trials in Brazil

Hungary3 sites

  • GSK Investigational Site

    Debrecen, 4043

  • GSK Investigational Site

    Győr, 9024

  • GSK Investigational Site

    Szeged, 6725

Other trials in Hungary

Portugal2 sites

  • GSK Investigational Site

    Coimbra, 3000-548

  • GSK Investigational Site

    Lisbon, 1649-035

Other trials in Portugal

Switzerland1 site

  • GSK Investigational Site

    Zurich, 8032

Other trials in Switzerland

About this study

Official title: A 54-week, Double-blind, Randomized, Placebo-controlled, Parallel-group Study to Investigate the Effects of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy to Donepezil on Cognition and Overall Clinical Response in APOE ε4-stratified Subjects With Mild to Moderate Alzheimer's Disease.

Rosiglitazone (RSG) has been tested in clinical studies and is approved by the FDA as a treatment for type II diabetes mellitus, a disease that occurs when the body is unable to effectively use glucose. RSG XR, the investigational drug used in this study, is an extended-release form of RSG.

This study tests whether RSG XR safely provides clinical benefit to people with mild to moderate Alzheimer's disease (AD) when combined with the currently approved AD medication, Aricept (donepezil). RSG XR is a new approach to AD therapy and this study tests a new way to treat AD by testing whether one's genetic makeup affects their response to the study drug. Clinical data suggesting that RSG may benefit AD patients was first seen in a small study performed at the University of Washington and then from a larger GSK study conducted in Europe and New Zealand. In the first study, subjects receiving RSG once daily for 6 months scored significantly better on 3 tests of memory and thought than those who did not receive RSG. In the GSK study, those that appeared to benefit most from treatment with RSG XR had a specific genetic pattern. They did not have the gene that caused them to produce the protein apolipoprotein E e4 (APOE e4). Subjects who have the APOE e4 gene may have two copies, one from each parent, or they may have only one APOE e4 gene meaning that they inherited either the APOE e2 or APOE e3 version of the gene, instead of APOE e4, from one of their parents. Subjects with one copy of the APOE e4 gene remained at their same level of thinking ability while those with two copies of the APOE e4 gene, continued to worsen during the 6-month treatment. The current study will more directly test the effectiveness or RSG XR on people who either have or lack the APOE e4 gene.

Read the detailed description

A 54-week, double-blind, randomized, placebo-controlled, parallel-group study to investigate the effects of rosiglitazone (extended release tablets) as adjunctive therapy to donepezil on cognition and overall clinical response in APOE e4-stratified subjects with mild to moderate Alzheimer's disease (REFLECT-2)

Being tested
Rosiglitazone Extended Release 2mg, Rosiglitazone Extended Release 8mg, Placebo, Donepezil
Keywords
apolipoprotein E, Alzheimer's disease, cognition, rosiglitazone, adjunctive therapy
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rosiglitazone Extended Release 2mgDrug

    Rosiglitazone Extended Release 2mg OD

  • Rosiglitazone Extended Release 8mgDrug

    Rosiglitazone Extended Release 8mg OD

  • PlaceboOther

    Placebo

  • DonepezilOther

    Also called Aricept

    Donepezil (At least 6 months of ongoing donepezil therapy for Alzheimer's disease, with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).

Study groups in NCT00348309
Study groupRoleWhat they receive
Arm 1ExperimentalRosiglitazone Extended Release 2mg OD
Receives: Drug: Rosiglitazone Extended Release 2mg; Other: Donepezil
Arm 2ExperimentalRosiglitazone Extended Release 8mg OD
Receives: Drug: Rosiglitazone Extended Release 8mg; Other: Donepezil
Arm 3Placebo comparatorPlacebo
Receives: Other: Placebo; Other: Donepezil

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48

    ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in participants with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the genetic subgroups. Least square mean is entered for adjusted mean.

    Measured: Baseline (Week 0) and Week 48

  2. Change From Baseline in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) at Week 48 for APOE E4

    CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change from baseline is calculated as Week 48 value minus the baseline value. APOE4 negative, All except E4/E4's: comprised of APOE4 negative and E4 heterozygote and full population was analyzed for this outcome measure. A hierarchical testing procedure was used to control for the two rosiglitazone dose groups and the genetic subgroups.

    Measured: Baseline (Week 0) and Week 48

Secondary outcomes (20)

  1. Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score

    The DAD measures instrumental and basic activities of daily living in participants with Alzheimer's Disease (AD). This scale assesses a participants' ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The scale includes 23 items relating to instrumental activities of daily living and 17 items relating to basic self-care. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. Total score was obtained by adding the rating for each question and converting this total score out of 100. The total score ranged from 0 to 100, where higher score indicated better function and lower score indicated greater severity of symptoms; a positive change from baseline indicated an improvement. Change from baseline is calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 8, 16, 24 and 48

  2. Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score

    The NPI is a questionnaire that quantifies behavioral changes in dementia. For each of 12 behavioral domains there are 4 scores: Frequency (scale:1=occasionally to 4=very frequently), Severity (scale:1=Mild to 3=Severe), Total (frequency x severity), Caregiver distress (scale: 0=not at all distressing to 5=extremely distressing).The NPI Psychosis Subscale consists of the two domains of Delusions and Hallucinations, calculated by adding the Individual Item Scores, to yield a possible total score of 0 to 24. Lower score=less severity. Change from baseline is calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 8, 16, 24 and 48

  3. Change From Screening in Mini Mental State Examination (MMSE) Total Score

    The MMSE consists of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. The scale was completed by the investigator, based on the performance of the participant, and took approximately 5 to 10 minutes to administer. The scores from 11 tests were combined to obtain the total score. The total scores range from 0 to 30, with lower scores indicating greater cognitive impairment and higher score indicating better outcome; a positive change from screening indicated an improvement. The total MMSE score for participants at screening was between 10 and 26, inclusive, in order to be eligible to participate in the trial. Change from screening is calculated as endpoint value minus the screening value.

    Measured: Screening (Week -4) and Week 48

  4. Change From Baseline in the Domains of the Resource Utilization in Dementia Scale (RUD)

    The RUD instrument was developed as a comprehensive tool to assess the amount of resource use among demented patients. RUD assessd both formal and informal resource use of the patient and the primary caregiver, making it possible to calculate costs from a societal perspective. Q1 corresponds to the number of hours during the last month the caregiver spent assisting the patient with toilet visits, eating, dressing, grooming, walking and bathing and Q2 corresponds to the number of hours during the last month the caregiver spent assisting the patient with shopping, food preparation, housekeeping, laundry, transportation, taking medication and managing financial matters. Change from Baseline was calculated as value at scheduled time point minus Baseline value. Baseline was defined as value at Week 0. Estimated value was calculated by Active treatment minus Placebo. The adjusted means were presented.

    Measured: Baseline (Week 0), Week 12, 24, 36 and 48

  5. Change From Baseline in European Quality of Life-5 Dimensions Proxy Version (EQ-5D Proxy) Scale Total Score Assessed by Thermometer (Visual Analog Scale [VAS]) and Utility

    The EQ-5D Proxy is a two part scale that evaluated the participant's health status via Thermometer and Utility scores. The Thermometer score was the caregiver's rating of the participant's overall health status on a VAS (0 ["worst possible status"] to 100 ["best imaginable status"]). The Utility score was a caregiver rating of health status on dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression] where '1' indicated better health state (no problems); '3' indicated worst health state ("confined to bed"). Total possible score was the sum of individual items, ranged from 5 to 15; lower score indicated a better health state and higher score indicated greater severity of symptoms. A positive change from baseline indicated improvement in the Thermometer score and a negative change from baseline indicated improvement in the Utility score. Change from baseline is calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 12, 36 and 48

  6. Change From Baseline in ADAS-Cog Total Score for Observed Cases at Weeks 8, 16, 24, 36 and 48

    ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change from baseline is calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 8, 16, 24, 36 and 48

  7. Change From Baseline in CDR-SB Score for Observed Cases at Weeks 12, 24, 36 and 48

    CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change from baseline is calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 12, 24, 36 and 48

  8. Change in ADAS-Cog Total Score for Observed Cases at Week 54 Compared to Week 48

    ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in patients with Alzheimer's Disease. The cognitive subscale of the ADAS (ADAS-Cog) comprises 11 items that are summed to a total score ranging from 0 to 70, with lower scores indicating less severe impairment. Change was calculated as endpoint value (Week 54) minus Week 48 value.

    Measured: Week 48 and 54

  9. Change in CDR-SB Total Score at Week 54 Compared to Week 48

    CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Change was calculated as endpoint value (Week 54) minus Week 48 value.

    Measured: Week 48 and 54

  10. Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 48

    Blood samples of participants were collected for HbA1c assessment. HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Change from Baseline in HbA1c was calculated as the value at Week 48 minus the value at Baseline.

    Measured: Baseline (Week 0) and Week 48

  11. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. The data was reported for prospective period.

    Measured: Up to Week 54

  12. Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP)

    The plethysmographic method was used to measure BP throughout the study. Change in Systolic and Diastolic BP was calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

  13. Mean Change From Baseline in Heart Rate

    Mean Change From Baseline in heart rate was calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

  14. Mean Change From Baseline in Weight

    Body weight was measured at all visits, without shoes and wearing light clothing. Mean Change From Baseline in Weight was calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

  15. Change From Baseline in Hemoglobin Values

    Blood samples of participants were collected for Hemoglobin. Change from baseline in Hemoglobin was calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 4, 16, 36 and 48

  16. Change From Baseline in Hematocrit Values

    Blood samples of participants were collected for Hematocrit . Change from baseline in Hematocrit was calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 4, 8, 12, 16, 36 and 48

  17. Mean Change From Baseline in Short Term Memory Assessment Score

    Short term memory assessment score was based on ADAS-Cog questionnaire (Question 1 and 7). ADAS is a performance-based test that measures specific cognitive and behavioral dysfunctions in participants with AD. Question 1 (Word Recall) and Question 7 (Word Recognition) of the ADAS-Cog questionnaire were summed to get a short term memory assessment score. Word recall task consist of the participants score was the mean number of words not recalled on three trials (maximum score 10) and word recognition task, to score this item the number of incorrect responses was counted (maximum error score was 12). The total score ranged from 0 to 22 with 0 indicating absence of symptoms and higher scores indicating greater dysfunction; a negative change from baseline indicated improvement. Change from Baseline in short term memory assessment was calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 8, 16, 24, 36, 48 and 56

  18. Change From Baseline in HbA1c at Week 12, Week 24 and Week 36

    Blood samples of participants were collected for HbA1c assessment. HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Change from Baseline in HbA1c was calculated as the value at time point minus the value at Baseline.

    Measured: Baseline (Week 0) and Week 12, 24 and 36

  19. Number of Participants With Laboratory Potential Clinical Concern (PCC) Values

    Only those parameters for which at least one value of clinical concern (CC) was reported are summarized. Pre-defined limits of potential clinical concern (CC Low [relative to the lower limit of normal], CC High [relative to the upper limit of normal]) are: Hematocrit 0.8, 1.2; hemoglobin 10-11, 16.5-18; Red blood corpuscles(RBC) 0.8, 1.2; mean corpuscular volume (MCV) 0.8, 1.2; mean corpuscular hemoglobin (MCH) 0.8, 1.2; White blood corpuscles (WBC) 3- absolute value, 15-absolute value, Red Cell Distribution Width (RDW) 0.8, 1.2; Lymphocytes 0.75, 1.5; Monocytes NA, 2; Eosinophil NA, 2; platelet count 100-absolute, 500-absoulte; segmented neutrophil (SN) 0.75, 1.5 and Total Neutrophil (TN) 0.75, 1.5.

    Measured: Baseline (Week 0), Week 4, 8, 12, 16, 24, 36, 48 and 56

  20. Change From Baseline in Alzheimer's Carer Quality of Life Instrument (ACQLI) Total Score

    The ACQLI was an assessment of caregiver quality of life. This instrument consists of 30 questions exploring various aspects of carer's quality of life. Each of the questions had a two point response and the 30 questions were summed to provide a total score. Items are assumed to be unidimensional (i.e., represent a single variable) and are scored 0/1 (false/true) before summation into a total score with a 0-30 range. The total score ranged from 0 to 30, where 0 indicated absence of symptoms and higher score indicated worse outcomes; a negative change from baseline indicated improvement. Change from baseline was calculated as endpoint value minus the baseline value.

    Measured: Baseline (Week 0), Week 12, 36 and 48

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jul 2006 (estimated)
  2. Study start6 Jul 2006
  3. Primary completion1 Jan 2009
  4. Study completion28 Jan 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,496 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00348309
Sponsor's protocol ID
AVA102672
Acronym
REFLECT-2
Status last verified
Sep 2017
First submitted
30 Jun 2006
Last updated
28 Nov 2017
Data monitoring committee
Yes
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Publications

  • Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B, Zvartau-Hind M, van Dyck CH, Gold M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Curr Alzheimer Res. 2011 Aug;8(5):592-606. doi: 10.2174/156720511796391935.

    PubMed 21592048

Questions about this trial

What is this clinical trial studying?

A study testing Rosiglitazone Extended Release 2mg, Rosiglitazone Extended Release 8mg and Donepezil in people with Alzheimer's Disease, run by GlaxoSmithKline at 249 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 249 sites in Germany, United States, France, Japan, Italy and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Nov 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 48 (time frame: Baseline (Week 0) and Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00348309, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2017.

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