WEBAPPENDIX 1, Study organization and changes in blood pressure

STUDY ORGANISATION

Data Safety Monitoring Board (DSMB) members

Ian Ford (Chair) / Independent Statistician / Professor of Statistics, The Robertson Centre for Biostatistics
University of Glasgow, University Avenue
Glasgow G12 8QQ, UK
Tom MacDonald / Cardiovascular Pharmacologist
Epidemiologist / Professor of Clinical Pharmacology & Pharmacoepidemiology
Medicines Monitoring Unit, Division of Medicine & Therapeutics,Ninewells Hospital & Medical School
Dundee DD1 9SY, UK
Meguid El Nahas / Nephrologist / Professor of Nephrology, Sheffield Kidney Institute
Northern General Hospital
Sheffield S5 7AU, UK
Steering Committee (SC) members
Giancarlo Viberti (Chair) / Diabetologist / Professor of Diabetes and Metabolic Medicine, Dept of Diabetes, Endocrinology & Internal Medicine
KCL Guy's Hospital, London,
London SE1 9RT, UK
Luis Miguel Ruilope / Nephrologist / Professor of Medicine, Head of Hypertension Unit
Hospital 12de Octobre
ES-28009 Madrid, Spain
Johannes F. Mann / Nephrologist / Professor of Medicine, Head Dept. of Nephrology, Hypertension and Rheumatology
Schwabing General Hospital, LMU,
DE-80804 Munich Germany
Kenneth Jamerson / Cardiovascular Medicine / Professor of Medicine, University of Michigan, Division of Cardiovascular Medicine,
24 Frank Lloyd Wright Drive,
Ann Arbor, MI 48106-0739 USA
Thomas Littke / Sponsor representative / Director of Clinical Operations, Speedel Pharma AG
Hirschgässlein 11,
CH-4051 Basel
Clinical Endpoint Committee (CEC) members
Sally Marshall (Co-Chair) / Diabetologist / Professor of Diabetes, University of Newcastle, Medical School,
Newcastle upon Tyne, NE2 4HH, UK
Matthew R. Weir (Co-Chair) / Nephrologist / Professor of Medicine, University of Maryland School of Medicine
Baltimore, MD, 21201, USA
Leif Erhardt / Cardiologist / Professor of Cardiology, Cardiology Research Unit,
Malmö University Hospital
SE-20502 Malmö, Sweden
José López-Sendón / Cardiologist / Director Cardiology Department, Planta 1
Hospital La Paz, Paseo de la Castellana 261
28046 Madrid, Spain
Andreas Terent MD PhD / Neurologist / Associate Professor, Department of Medicine
Uppsala University Hospital
SE-751 85 Uppsala, Sweden
Svend Stradgaard / Neurologist / Department of Neurology
Herlev University Hospital
DK-2730 Herlev, Denmark
Michael Weber / Cardiologist / Professor of Medicine and Associate Dean for Research
SUNY Downstate College of Medicine
Brooklyn, NY, USA

Speedel also appointed the contract reasearch organisation Quintiles Ltd (hereafter referred to as ‘Quintiles’) for the study set-up, initiation, monitoring, data management, statistical analysis, preparation and submission of various applications. Clinical trial supply management was provided by Aptuit Ltd, Scotland. Pharmacokinetic analyses were performed by RCC GmbH, Basle, Switzerland

Contract Research Organisation (CRO) / Quintiles Ltd
Bracknell, UK
CRO Study Physicians / Richard Levine, MD
Quintiles Inc.
Rockville, Maryland, US
Ian Escudero, MD
Quintiles East Asia Pte Ltd, Singapore / Juan Gispert, MD
Quintiles s.l.
Madrid, Spain
CRO Project Director / Sharyn Hynds, PhD
Quintiles Ltd
Bathgate, UK
CRO Statisticians / Michael O’Kelly, PhD
Quintiles Ireland
Dublin, Ireland
Jonathan Smith, PhD
Quintiles Inc.
Research Triangle Park, North Carolina, US / Damian Green
Quintiles France
Strasbourg, France
Clinical Trial Supply Management / Aptuit (Edinburgh) Ltd[1]
Bathgate, UK
Central Laboratory Facilities / Europe:
Quintiles Laboratories Europe, Livingston,
UK / Latin America:
Quintiles Laboratories Coordination Center
Buenos Aires,
Argentina
USA:
Quintiles Laboratories Ltd
Atlanta, Georgia,
US / Singapore:
Quintiles Laboratories East Asia,
Singapore

Changes in blood pressure

Sitting DBP: changes from Baseline

------Treatment group=25mg------

Variable N Mean Std Dev Minimum Maximum P-Value vs Placebo

______

Month 3 242 -3.0619835 9.9892204 -40.0000000 30.0000000 0.0198

Month 6 160 -4.4000000 9.9414639 -30.0000000 20.0000000 0.0028

______

------Treatment group=50mg------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 244 -3.9672131 9.7016688 -36.0000000 28.0000000 0.0028

Month 6 168 -3.5952381 10.8607066 -38.0000000 20.0000000 0.1183

______

------Treatment group=Placebo------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 289 -0.2387543 10.1184866 -32.0000000 44.0000000

Month 6 201 -0.1890547 9.9012161 -25.0000000 30.0000000

______

Sitting SBP: changes from Baseline

------Treatment group=25mg------

The MEANS Procedure

Variable N Mean Std Dev Minimum Maximum

______

Month 3 242 -4.0826446 16.0080824 -50.0000000 84.0000000 0.0875

Month 6 160 -4.3312500 17.6463234 -60.0000000 55.0000000 0.0935

______

------Treatment group=50mg------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 244 -4.4098361 16.7421767 -48.0000000 40.0000000 0.0216

Month 6 168 -6.1011905 18.2893051 -65.0000000 52.0000000 0.0175

______

------Treatment group=Placebo------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 289 0.5397924 17.3823218 -54.0000000 79.0000000

Month 6 201 -0.5174129 18.2425586 -46.0000000 50.0000000

______

Standing DBP: changes from Baseline

------Treatment group=25mg------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 237 -3.4514768 10.0352540 -47.0000000 22.0000000 0.0545

Month 6 158 -3.9177215 10.5914069 -37.0000000 20.0000000 0.2266

______

------Treatment group=50mg------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 243 -4.0329218 10.5813919 -32.0000000 30.0000000 0.0029

Month 6 168 -3.9642857 11.0707539 -43.0000000 22.0000000 0.2161

______

------Treatment group=Placebo------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 289 -0.6124567 10.3606151 -40.0000000 35.0000000

Month 6 200 -1.0000000 10.2437627 -30.0000000 32.0000000

______

Standing SBP: changes from Baseline

------Treatment group=25mg------

p-value vs

Variable N Mean Std Dev Minimum Maximum placebo

______

Month 3 237 -4.0379747 17.1287075 -68.0000000 84.0000000 0.0575

Month 6 158 -3.1202532 17.0765819 -58.0000000 44.0000000 0.6512

______

------Treatment group=50mg------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 243 -3.1646091 17.3123249 -60.0000000 48.0000000 0.0285

Month 6 168 -6.0773810 19.3647612 -60.0000000 54.0000000 0.0295

______

------Treatment group=Placebo------

Variable N Mean Std Dev Minimum Maximum

______

Month 3 289 0.9965398 17.1590797 -50.0000000 102.0000000

Month 6 200 -0.9150000 18.7299715 -56.0000000 56.0000000

______

ANOVA controlling for inv. centre