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,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Joint Meeting of the Anti-Infective Drugs Advisory Committee and the Drug Safety and Risk Management Committee Meeting,December 14&15,2006,Anti-Infective Drug Products and Drug Safety and Risk ManagementAdvisory Committees Meeting,December 14&15,2006,Edward Cox,MD MPH,Acting Director,Office of Antimicrobial Products,OND/CDER/FDA,1,Welcome,Welcome,Topic for discussion,NDA 21-144 Ketek,(telithromycin)Tablets,Overall benefits and risks based upon what we know today,Information in the original NDA&the additional information that we have since the drugs was approved in April 2004,Primary purpose of the meeting,To seek the Advisory Committees advice on the overall assessment of risks and benefits of Ketek for each of its approved indications based upon what we know today,2,Ketek(telithromycin),Complex NDA Review,Spanned 3 review cycles,March 2000 to April 2004,2 Previous FDA Anti-Infective Drug Product Advisory Committees,April 2001&January 2003,Ketek(telithromycin)Tablets-Approved in April 2004,3,Ketek Indications,INDICATIONS AND USAGE,KETEK tablets are indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below for patients 18 years old and above.,Acute bacterial exacerbation of chronic bronchitis,due to,Streptococcus pneumoniae,Haemophilus influenzae,or,Moraxella catarrhalis,.,Acute bacterial sinusitis,due to,Streptococcus pneumoniae,Haemophilus influenzae,Moraxella catarrhalis,or,Staphylococcus aureus,.,Community-acquired pneumonia,(of mild to moderate severity)due to,Streptococcus pneumoniae,(including multi-drug resistant isolates MDRSP*),Haemophilus influenzae,Moraxella catarrhalis,Chlamydophila pneumoniae,or,Mycoplasma pneumoniae,.,4,Other Drugs with Similar Indications,Acute bacterial sinusitis,amoxicillin,amoxicillin/clavulanate,cefdinir,cefpodoxime proxetil,cefprozil,cefuroxime axetil,loracarbef,azithromycin,clarithromycin,ciprofloxacin,levofloxacin,moxifloxacin,Acute bacterial exacerbation of chronic bronchitis,cefaclor,cefdinir,cefditoren pivoxil,cefixime,cefpodoxime proxetil,cefprozil,ceftibuten,cefuroxime axetil,loracarbef,azithromycin,clarithromycin,dirithromycin,gemifloxacin,levofloxacin,lomefloxacin,moxifloxacin,ofloxacin,trimethoprim/sulfamethoxazole,Community-acquired pneumonia,amoxicillin/clavulanate,cefdinir,cefditoren pivoxil,cefpodoxime proxetil,loracarbef,azithromycin,clarithromycin,dirithromycin,gemifloxacin,levofloxacin,moxifloxacin,linezolid,Lower respiratory tract infections,(past indication-AECB&CAP),amoxicillin,amoxicillin/clavulanate,erythromycin,cefaclor,ciprofloxacin,5,Other Drugs with“Older Related Indications,Amoxicillin,Infections of the ear,nose,and throat,due to,Streptococcus,spp.(alpha and beta hemolytic strains only),Streptococcus pneumoniae,Staphyloccocus spp,.,or,H.influenzae,Ampicillin,Infections of the respiratory tract,:non-penicillinase producing,H.influenzae,and staphylococci,and streptococci including,Streptococcus pneumoniae,Tetracycline&Doxycycline,Respiratory tract infections,caused by,M.pneumoniae,Respiratory tract infections,caused by,H.influenzae and Klebsiella,spp.,(when susceptibility testing indicates appropriate),Upper Respiratory tract infections,caused by,S.pneumoniae,(formerly,Diplococcus pneumoniae,),(when susceptibility testing indicates appropriate),6,Demonstrating Efficacy Historical Perspective-1,The science of clinical trial design has advanced over time,1938 Federal Food,Drug and Cosmetic(FD&C)Act-Pre-clearance of drugs for safety&Pre-market notification,did not include evaluation of efficacy,1962 Kefauver Harris Amendments added a requirement that drugs be shown to be effective,Required a positive act of approval before a new drug could be marketed,Required that the FDA review all drugs approved since 1938 for effectiveness,Efficacy of earlier antibiotics approved from 1938-1962 were evaluated as part of the Drug Efficacy Study Implementation(DESI)review,7,Demonstrating Efficacy Historical Perspective-2,Post 1962-Efficacy studies that enrolled patients with any of a variety of different infections in the same study,1992 Points to Consider and 1992 IDSA/FDA guidelines in Clinical Infectious Diseases 1992-Indication specific trials,including active controlled studies designed to equivalence or superiority,1998 Draft Guidances similar or superior effectiveness to an approved product in indication specific trials,More recently,questions on the ability of non-inferiority studies to provide informative data on efficacy in milder,typically self-limited infections,8,Clinical Studies-Ketek,A number of clinical studies including studies in:,CAP,AECB,ABS,Active controlled trials designed to show non-inferiority,9,Adequate and well controlled studies,21 CFR,314.126 Adequate and well-controlled studies.(a)The purpose of conducting clinical investigations of a drug is to distinguish the effect of a
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