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.
Welcome and Background Douglas
Throckmorton, M.D.
Director, Division of Cardiovascular and Renal Drug
Products, CDER, FDA
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.
Conclusions Jeremy
Ruskin, M.D.
AGENDA (cont.)
Introduction Mary
Taylor, M.P.H.
Vice
President
Regulatory
Affairs
Bayer
Pharmaceuticals Corporation
Assessment of the QT/QTc Thomas Segerson, M.D.
Effect of Vardenafil Vice
President
Medical
and Scientific Affairs
Bayer
QT/QTc Study Design, Joel
Morganroth, M.D.
Heart Rate Correction & Clinical
Professor of Medicine
Risk of Cardiac Arrhythmia
Chief
Scientist
eResearch Technology
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.
Special Government Employee
(SGE) Consultants (voting)
Jean T. Barbey, M.D.
Assistant Professor
Medicine and Pharmacology
Acting Director, Division of Clinical Pharmacology
L. Gay Bernitsky, M.D.
Urology Network of
5501 Jefferson
NE, Suite 700
Albuquerque, New
Mexico 87109
Philip Hanno, M.D.
Division of Urology, Hospital of the
Medical Director
Department of Clinical Effectiveness and Quality
Improvement
Peter Kowey, M.D.
Professor of
Medicine,
Chief of Cardiology,
Edward L.C. Pritchett, M.D.
Consulting Professor of Medicine
Divisions of Cardiology and Clinical Pharmacology
P.O.
SGE Consultant (non-voting)
Dan M. Roden, M.D.
Professor of Medicine and Pharmacology
Chief, Division of Clinical Pharmacology
Division of Clinical Pharmacology
John Neylan, M.D.
Vice President, Clinical Research and Development
Wyeth Research
· 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
· Culley Carson, M.D.
Professor
and Chief of Urology