Presentation is loading. Please wait.

Presentation is loading. Please wait.

Uprima ® (apomorphine HCl tablets) sublingual Presentation to the Urology Subcommittee of the Advisory Committee for Reproductive Health Drugs April 10,

Similar presentations


Presentation on theme: "Uprima ® (apomorphine HCl tablets) sublingual Presentation to the Urology Subcommittee of the Advisory Committee for Reproductive Health Drugs April 10,"— Presentation transcript:

1 Uprima ® (apomorphine HCl tablets) sublingual Presentation to the Urology Subcommittee of the Advisory Committee for Reproductive Health Drugs April 10, 2000 TAP HOLDINGS INC. E Primary 1 4/26/2015

2 E Primary 2 4/26/2015 Uprima ® Speakers James Freston, M.D., Ph.D. Professor of Medicine and Clinical Pharmacology University of Connecticut Health Center James Freston, M.D., Ph.D. Professor of Medicine and Clinical Pharmacology University of Connecticut Health Center Barbara Bopp, Ph.D. Manager, Drug Metabolism and Pharmacology TAP Holdings Inc. Barbara Bopp, Ph.D. Manager, Drug Metabolism and Pharmacology TAP Holdings Inc. Jeremy Heaton, M.D. Professor, Dept. of Urology, Dept. of Pharmacology & Toxicology Queens University Kingston, Ontario, Canada Jeremy Heaton, M.D. Professor, Dept. of Urology, Dept. of Pharmacology & Toxicology Queens University Kingston, Ontario, Canada Timothy Fagan, M.D. Professor of Medicine and Associate Professor of Pharmacology University of Arizona College of Medicine Timothy Fagan, M.D. Professor of Medicine and Associate Professor of Pharmacology University of Arizona College of Medicine Introduction

3 E Primary 3 4/26/2015 Uprima ® TAP Participants John Seely, Ph.D. Vice President, Research and Development John Seely, Ph.D. Vice President, Research and Development Dean Sundberg Director, Regulatory Affairs Dean Sundberg Director, Regulatory Affairs Karl Agre, M.D., Ph.D. Senior Director, Medical Affairs Karl Agre, M.D., Ph.D. Senior Director, Medical Affairs Susan Buttler, M.S. Associate Director, Clinical Development Susan Buttler, M.S. Associate Director, Clinical Development Dennis Jennings, Ph.D. Director of Scientific Data Analysis Dennis Jennings, Ph.D. Director of Scientific Data Analysis James Lancaster, Ph.D. Manager, Clinical Statistics James Lancaster, Ph.D. Manager, Clinical Statistics Introduction

4 E Primary 4 4/26/2015 Uprima ® TAP Participants (cont.) Anthony Edmonds, M.S. Senior Statistician Anthony Edmonds, M.S. Senior Statistician Dustin Ruff, Ph.D. Statistician Dustin Ruff, Ph.D. Statistician Renee Perdok, M.S. Statistician Renee Perdok, M.S. Statistician Farrel Fort, Ph.D., D.A.B.T. Manager, Drug Safety Farrel Fort, Ph.D., D.A.B.T. Manager, Drug Safety Introduction

5 E Primary 5 4/26/2015 Uprima ® TAP Consultants Cully Carson, M.D. Chief - Division of Urology University of North Carolina Chapel Hill, NC Cully Carson, M.D. Chief - Division of Urology University of North Carolina Chapel Hill, NC Eugene Dula, M.D. Medical Director Western Urologic Associates Van Nuys, CA Eugene Dula, M.D. Medical Director Western Urologic Associates Van Nuys, CA Ronald Lewis, M.D. Professor of Urology Medical College of Georgia Augusta, GA Ronald Lewis, M.D. Professor of Urology Medical College of Georgia Augusta, GA Arnold Melman, M.D. Department of Urology Montefiore Hospital Bronx, NY Arnold Melman, M.D. Department of Urology Montefiore Hospital Bronx, NY Introduction

6 E Primary 6 4/26/2015 Uprima ® TAP Consultants Ray Rosen, Ph.D. Department of Psychiatry Robert Wood Johnson Medical School Piscataway, NJ Ray Rosen, Ph.D. Department of Psychiatry Robert Wood Johnson Medical School Piscataway, NJ Addison Taylor, M.D. Professor of Medicine and Clinical Pharmacology Baylor College of Medicine Houston, TX Addison Taylor, M.D. Professor of Medicine and Clinical Pharmacology Baylor College of Medicine Houston, TX Joel Morganroth, M.D. Chief Executive Officer Premier Research Philadelphia, PA Joel Morganroth, M.D. Chief Executive Officer Premier Research Philadelphia, PA Gary G. Koch, Ph.D. Statistical Consultant Chapel Hill, NC Gary G. Koch, Ph.D. Statistical Consultant Chapel Hill, NC Introduction

7 E Primary 7 4/26/2015 Uprima ® TAP Presentations General Introduction….…….……..…………………….Dr. Freston General Introduction….…….……..…………………….Dr. Freston Apomorphine Pharmacokinetics and Metabolism……Dr. Bopp Apomorphine Pharmacokinetics and Metabolism……Dr. Bopp ED Treatments……………………………………………Dr. Heaton ED Treatments……………………………………………Dr. Heaton Summary of Efficacy….……....…………………………Dr. Heaton Summary of Efficacy….……....…………………………Dr. Heaton Summary of Safety.….……...…………………………..Dr. Freston, Dr. Fagan Summary of Safety.….……...…………………………..Dr. Freston, Dr. Fagan Benefit-Risk Assessment/Summary…………..……….Dr. Freston Benefit-Risk Assessment/Summary…………..……….Dr. Freston Introduction

8 E Primary 8 4/26/2015 Uprima ® Topics Identified in FDA Briefing Document Comparison to other marketed ED drugs Comparison to other marketed ED drugs Representative ED patient population Representative ED patient population Pharmacokinetic variabilty Pharmacokinetic variabilty Clinical relevance of 2 mg Clinical relevance of 2 mg Efficacy in diabetics Efficacy in diabetics Discontinuations in long-term studies Discontinuations in long-term studies Hemodynamics Hemodynamics Nitrate interaction Nitrate interaction Alcohol interaction Alcohol interaction Introduction

9 E Primary 9 4/26/2015 Uprima ® Erectile dysfunction is the “inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance” NIH Consensus Development Panel on Impotence JAMA 270: 83-90, 1993 Definition Erectile Dysfunction (ED) Introduction-ED

10 E Primary 10 4/26/2015 Uprima ® Laumann EO, Paik P, Rosen RC. JAMA 1999;281(6): Erectile Dysfunction US National Health and Social Life Survey (NHSLS)-1992 US National Health and Social Life Survey (NHSLS)-1992 –Probability sample study of sexual behavior in men and women –Demographically representative cohort of 1,410 men, ages –Correlated ED to other diagnoses –ED in 10% of men, ages Epidemiology and Demographics Introduction-ED

11 E Primary 11 4/26/2015 Uprima ® Feldman et al. J. Urology 151: 54-61, Epidemiology and Demographics Erectile Dysfunction Massachusetts Male Aging Study (MMAS) – Massachusetts Male Aging Study (MMAS) – –Cross-sectional, community-based, random sample survey of 1,300 men, ages –Overall ED rate 52% -Complete 10% -Moderate 25% -Minimal 17% –Extrapolation to US: 30 million men with ED –ED correlated with age, health status, emotional function Introduction-ED

12 E Primary 12 4/26/2015 Uprima ® Age Related Changes in Erectile Status Age % Extracted from Feldman et al. J. Urology 151: 54-61, Massachusetts Male Aging Study (MMAS) Introduction-ED

13 E Primary 13 4/26/2015 Uprima ® Feldman et al. J. Urology 151: 54-61, Johannes et al. J. Urology 163: , ED is Associated with: Massachusetts Male Aging Study Age Age Diabetes Diabetes Hypertension Hypertension Heart disease Heart disease Medications Medications Depression Depression Psychological factors Psychological factors Introduction-ED

14 E Primary 14 4/26/2015 Uprima ® Uprima ® StudiesMMAS 1 Duration of ED (mean)4.8 years Medical Condition (%) Hypertension31%33% Coronary Artery Disease (CAD)16%16% Hyperlipidemia16%— Diabetes16%9% ED Population 1 Johannes et al. J. Urology 163: , Introduction-Uprima

15 E Primary 15 4/26/2015 Uprima ® Introduction to Apomorphine USP drug USP drug Used as a pharmacologic agent since 1869 Used as a pharmacologic agent since 1869 –Over 1,100 literature citations –Therapeutic doses ranged from 0.2 to 1500 mg –Approximately 8,000 patients/subjects treated in clinical trials Approved in 12 countries for multiple indications, including Parkinson’s Disease Approved in 12 countries for multiple indications, including Parkinson’s Disease –Daily administration –Usual dose 3 to 30 mg, subcutaneously Dopaminergic properties recognized in 1967 Dopaminergic properties recognized in 1967 Central erectogenic effect recognized in the late 1970’s Central erectogenic effect recognized in the late 1970’s Activates DA receptors in hypothalamic and limbic neural pathways Activates DA receptors in hypothalamic and limbic neural pathways Introduction-Uprima

16 E Primary 16 4/26/2015 Uprima ® Introduction to Uprima ® Formulated to treat erectile dysfunction Formulated to treat erectile dysfunction Delivered sublingually (SL) Delivered sublingually (SL) Unique central mechanism of action Unique central mechanism of action Rapid onset of action Rapid onset of action Effective for erectile dysfunction (ED) in a wide spectrum of organic and non-organic etiologies and severities Effective for erectile dysfunction (ED) in a wide spectrum of organic and non-organic etiologies and severities Introduction-Uprima

17 E Primary 17 4/26/2015 Uprima ® Introduction to Uprima ® Safety Safety –No deaths –No myocardial infarctions (MI) related to study drug –No cerebrovascular accidents (CVAs) related to study drug –No priapism Nausea was the most frequent adverse event, syncope the most significant Nausea was the most frequent adverse event, syncope the most significant Introduction-Uprima

18 E Primary 18 4/26/2015 Uprima ® Uprima ® is indicated for the treatment of erectile dysfunction Proposed Indication

19 E Primary 19 4/26/2015 Uprima ® Doses Proposed doses: 2, 3 and 4 mg Uprima ® will be available as a sublingual tablet

20 E Primary 20 4/26/2015 Uprima ® Rationale for Uprima ® Treatment of ED ED is associated with a number of diseases and conditions ED is associated with a number of diseases and conditions Drugs with different modes of action are desirable as with other disorders with complex pathophysiology, e.g., hypertension, depression Drugs with different modes of action are desirable as with other disorders with complex pathophysiology, e.g., hypertension, depression Current therapies are limited: Current therapies are limited: –No drug is effective in all patients –Each drug has its own unique adverse event profile –The currently approved agents work by peripheral mechanisms Treatment is strongly influenced by couple and physician choice Treatment is strongly influenced by couple and physician choice New drugs with different mechanisms offer significant potential benefits New drugs with different mechanisms offer significant potential benefits Introduction-Uprima

21 E Primary 21 4/26/2015 Uprima ® Rationale for Uprima ® Treatment of ED Uprima ® has a: Uprima ® has a: –Unique central mechanism of action –Novel delivery system –Rapid onset Uprima ® has been studied in 27 clinical trials and has been shown to be a safe and effective treatment for ED in patients with and without known organic diseases Uprima ® has been studied in 27 clinical trials and has been shown to be a safe and effective treatment for ED in patients with and without known organic diseases Introduction-Uprima

22 E Primary 22 4/26/2015 Uprima ® (N = 3,035) Phase III Phase III –Three controlled crossover –Dose-optimization -One controlled parallel -Five long-term, open-label -One first dose administered at home Uprima ® Clinical Trials Phase I Phase I –Pharmacokinetics –Metabolic fate –Elderly (  65 years) –Renal/Hepatic Impaired –Drug interactions (Zofran ®, Compazine ® ) Special Phase I/II/III Special Phase I/II/III –Antihypertensives and nitrates –Diabetics –Alcohol –Prostatectomy –Spinal cord injury Introduction/Uprima


Download ppt "Uprima ® (apomorphine HCl tablets) sublingual Presentation to the Urology Subcommittee of the Advisory Committee for Reproductive Health Drugs April 10,"

Similar presentations


Ads by Google