Food and Drug Administration

Center for Drug Evaluation and Research (CDER)


Cardiovascular and Renal Drugs Advisory Committee

99th Meeting

May 29, 2003


Holiday Inn, Silver Spring

8777 Georgia Avenue, Silver Spring, MD




8:00 Call to Order and Opening Remarks Jeffrey Borer, M.D., Chair


Introduction of Committee


Conflict of Interest Statement Jayne E. Peterson, R.Ph., J.D. Executive Secretary, FDA



QT prolongation issues associated with two new drug applications (NDAs): (1) NDA 21-287, (alfuzosin HCl), Sanofi-Synthelabo Inc., for the proposed indication of treatment of the signs and symptoms of benign prostatic hyperplasia; and (2) NDA 21-400, Levitra (vardenafil HCl), Bayer Corp., proposed for the indication of treatment of erectile dysfunction. The discussion will focus on: (1) Clinical trial designs for the assessment of QT prolongation; (2) approaches to the correction of QT interval for drugs that affect the heart rate; and (3) risks of cardiac arrythmias associated with different degrees of QT prolongation. Premarketing clinical safety data from these applications and postmarketing safety data relevant to cardiac QT prolongation from drugs in the same two drug classes (i.e., alpha adrenergic blockers and phosphodiesterase type 5 inhibitors) will be considered.


8:15 FDA Presentation

Welcome and Background Douglas Throckmorton, M.D.

Director, Division of Cardiovascular and Renal Drug

Products, CDER, FDA


8:30 Sponsor Presentations

Sanofi-Synthelabo Inc.

Background Jon Villaume, Ph.D.

Sanofi-Synthelabo Inc.


Pharmacokinetics Jim Oppermann, Ph.D.

Sanofi-Synthelabo Inc.


ECG Studies Wocjiech Zareba, M.D., Ph.D.

University of Rochester


Conclusions Jeremy Ruskin, M.D.

Massachusetts General Hospital


9:20 Questions from Committee to Sponsor

Cardiovascular and Renal Drugs Advisory Committee

May 29, 2003

AGENDA (cont.)

9:30 Bayer Corporation

Introduction Mary Taylor, M.P.H.

Vice President

Regulatory Affairs North America

Bayer Pharmaceuticals Corporation

Assessment of the QT/QTc Thomas Segerson, M.D.

Effect of Vardenafil Vice President

Medical and Scientific Affairs

Bayer Canada


QT/QTc Study Design, Joel Morganroth, M.D.

Heart Rate Correction & Clinical Professor of Medicine

Risk of Cardiac Arrhythmia University of Pennsylvania

Chief Scientist

eResearch Technology


10:20 Questions from Committee to Sponsor


10:30 Break


10:45 FDA Presentations

Introduction Donna Griebel, M.D.

Deputy Director, Division of

Reproductive and Urologic Drug

Products, CDER, FDA


Effect of alfuzosin on QT Interval Venkat Jarugula, Ph.D.

Clinical Pharmacology and

Biopharmaceutics Reviewer, FDA


Effect of vardenafil on QT Interval Leslie Kenna, Ph.D.

Clinical Pharmacology and

Biopharmaceutics Reviewer, FDA


Safety Summary: Adverse events Marcea Whitaker, M.D.

potentially related to QT prolongation Medical Officer, FDA

or Torsade de Pointes


Summary of Review Issues Donna Griebel, M.D.


11:45 Questions from Committee to FDA


12:00 Lunch


1:00 Open Public Hearing


2:00 Committee Discussion and Response to FDA Questions


3:00 Break


3:15 Continuation of Committee Discussion and Response to FDA Questions


Cardiovascular and Renal Drugs Advisory Committee

99th Meeting

May 29, 2003


Special Government Employee (SGE) Consultants (voting)


Jean T. Barbey, M.D.

Assistant Professor

Medicine and Pharmacology

Acting Director, Division of Clinical Pharmacology

Georgetown University

3900 Reservoir Road

Washington, DC 20007


L. Gay Bernitsky, M.D.

Urology Network of New Mexico, LLC

5501 Jefferson NE, Suite 700

Albuquerque, New Mexico 87109


Philip Hanno, M.D.

Division of Urology, Hospital of the University of Pennsylvania

Medical Director

Department of Clinical Effectiveness and Quality Improvement

University of Pennsylvania Health System

Philadelphia, Pennsylvania


Peter Kowey, M.D.

Professor of Medicine, Jefferson Medical College

Chief of Cardiology, Lankenau Hospital and Main Line Health System

Lankenau Medical Office Building

100 Lancaster Avenue, Suite 556

Wynnewood, Pennsylvania 19096


Edward L.C. Pritchett, M.D.

Consulting Professor of Medicine

Divisions of Cardiology and Clinical Pharmacology

Duke University Medical Center

P.O. Box 2785

Durham, North Carolina 27715


SGE Consultant (non-voting)


Dan M. Roden, M.D.

Professor of Medicine and Pharmacology

Chief, Division of Clinical Pharmacology

Division of Clinical Pharmacology

Vanderbilt University School of Medicine

Nashville, Tennesse


Acting Industry Representative (non-voting)


John Neylan, M.D.

Vice President, Clinical Research and Development

Wyeth Research

500 Ariola Road

Collegeville, Pennsylvania 19426

Cardiovascular and Renal Drugs Advisory Committee

99th Meeting

May 29, 2003


Open Public Hearing Speakers



       Pfizer Incorporated (two speakers):


Michael Sweeney, M.D.

Senior Medical Director

Pfizer Incorporated


Rodney Falk, M.D.

Professor of Medicine

Director of Clinical Cardiology

Research and Associate Director of Boston University

Boston Medical Center

Boston, Massachusetts





       Culley Carson, M.D.

Professor and Chief of Urology

University of North Carolina

Chapel Hill, North Carolina