Datasets:

asafd60

/

LiLT_Processed

like 0

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[ "EXHIBIT", "Ant", "THE", "UPJOHN", "COMPANY", "KALAMAZOO.", "MICHIGAN", "49001", "0199.", "U.5.4.", "TELEPHONE:", "(616)", "323", "4000", "J.", "R.", "MITCHELL,", "MD.,", "P.", "D.", "Vice", "Chairman", "of", "the", "doand", "PAR.", "September", "21,", "1993", "Tai", "Matsuzawa,", "Ph.D.", "Managing", "Director", "Vice", "President,", "Pharmaceutical", "Group", "Takeda", "Chemical", "Industries,", "Lid.", "1-1,", "Doshomachi", "4-Chome", "Chuo", "Ku,", "Osaka", "541", "Japan", "Dear", "Doctor", "Matsuzawa:", "As", "you", "know,", "Upjohn", "has", "committed", "to", "notify", "Takeda", "by", "October", "1,", "1993,", "of", "our", "intentions", "regarding", "further", "clinical", "development", "of", "pioglitazone.", "On", "September", "20", "our", "Pharmaceutical", "Executive", "Council,", "Upjohn's", "highest", "scientific", "decision", "making", "body,", "carefully", "reviewed", "the", "results", "of", "the", "toxicology", "and", "clinical", "studies.", "The", "decision", "of", "the", "Council", "was", "that", "Upjohn", "will", "not", "go", "forward", "with", "pioglitazone", "in", "the", "clinic.", "The", "Council", "decided", "that", "further", "clinical", "development", "of", "pioglitazone", "could", "not", "be", "justified", "based", "on", "their", "concern", "regarding", "pioglitazone's", "margin", "of", "safety.", "As", "a", "consequence", "of", "this", "decision,", "Upjohn", "also", "must", "decline", "participation", "with", "Takeda", "on", "the", "proposed", "pioglitazone", "study", "in", "Canada.", "It", "is", "with", "deep", "regret", "that", "I", "convey", "this", "message,", "As", "you", "know", "Upjohn", "and", "Takeda", "enjoy", "a", "strong", "and", "beneficial", "relationship", "based", "on", "mutual", "respect.", "It", "is", "a", "great", "disappointment", "to", "us", "that", "we", "will", "not", "have", "the", "opportunity", "of", "further", "interactions", "and", "collaboration", "with", "Takeda", "on", "this", "project.", "Hopefully,", "we", "will", "find", "other", "opportunities", "for", "collaboration", "in", "the", "future.", "I", "have", "instructed", "my", "staff", "to", "work", "closely", "with", "Takeda", "personnel", "in", "regards", "to", "the", "release", "of", "any", "information,", "data,", "FDA", "notifications,", "and", "other", "issues", "to", "ensure", "Takeda's", "interests", "and", "wishes", "are", "followed.", "With", "best", "personal", "regards.", "Sincerely,", "President,", "Upjohn", "Laboratories", "Worldwide", "Research,", "Development,", "&", "Medical", "Affairs", "CONFIDENTIAL", "-", "SUBJECT", "TO", "PROTECTIVE", "ORDER", "UPJ-0065603", "Source:", "https://www.indupoo02", "oooo-nts.ucsf.edu/docs/lljf0226" ]

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[ "FROM", "HERETAN", "DEMAS", "FAX05-6204-2943", "19994", "18218", "(*)", "21", "31/21", ":", "28/x56:480:", "941295", "F", "1", "Takeda", "Chemical", "Industries,", "Ltd.", "Takeda", "Product", "Planning", "&", "Management", "Dept.,", "International", "Division", "1-1", "Doshomachi", "4-chome,", "Chuo-Ku,", "Osaka", "541,", "JAPAN", "Tel:", "+81", "6", "(204)", "2852", "Fax:", "+81", "6", "(204)", "2943", "TELEFAX", "MESSAGE", "To:", "E.", "Lilly", "&", "Company", "Date:", "January", "21,", "1999", "Att:", "Mr.", "Larry", "Ellingson", "From:", "Kunio", "Iwatani", "Executive", "Director", "Actos", "Product", "Team", "CC:", "Mr.", "Hamanaka,", "TPA", "Subject:", "Upjohn", "Matter", "Dear", "Mr.", "Ellingson,", "Enclosed", "please", "find", "a", "copy", "of", "Upjohn's", "letter", "to", "US", "FDA", "dated", "January", "7,", "1994.", "In", "the", "letter", "Upjohn", "said", "that", "in", "preliminary", "clinical", "evaluation", "in", "the", "United", "States,", "pioglitazone", "did", "not", "satisfy", "Upjohn's", "internal", "requirement", "for", "reduction", "blood", "glucose;", "therefore,", "the", "considerable", "programs", "required", "for", "development", "of", "pioglitazone", "are", "not", "in", "line", "with", "Upjohn's", "business", "needs.", "-..", "They", "did", "not", "mention", "about", "safety", "of", "pioglitazone.", "After", "Upjohn's", "decision,", "Takeda", "approached", "FDA", "and", "consulted", "whether", "Takeda", "might", "go", "further", "the", "clinical", "development", "works", "on", "pioglitazone.", "Since", "the", "FDA's", "response", "was", "positive", "to", "go", "ahead,", "Takeda", "took", "over", "Upjohn's", "works", "and", "finally", "filed", "NDA", "on", "January", "15,", "1999.", "This", "is", "the", "story", "of", "the", "fact.", "Although", "there", "may", "be", "rumors", "about", "the", "reasons", "of", "Upjohn's", "abandonment", "of", "pioglitazone", "development,", "specially", "from", "the", "viewpoints", "of", "safety", "issues,", "it", "might", "be", "advisable", "for", "us", "to", "keep", "saying", "that", "Upjohn's", "decision", "is", "based", "on", "JAN", "21", "'99", "07:43", "DALY", "19", "06", "6204", "2943", "PAGE", ".", "01", "Confidential", "-", "Subject", "to", "Protective", "Order", "LLY-CRCARCH-00003000", "Source:", "https://www.indupbodsfoodonts.ucsf.edu/docs/nljf0226" ]

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[ "Takeda", "In", "light", "of", "age-related", "risks", "(especially", "bladder", "cancer,", "fractures", "and", "heart", "failure),", "the", "balance", "of", "benefits", "and", "risks", "should", "be", "considered", "carefully", "both", "before", "and", "during", "treatment", "in", "the", "elderly;", "Bladder", "Cancer", "Cases", "of", "bladder", "cancer", "were", "reported", "more", "frequently", "in", "a", "meta-analysis", "of", "controlled", "clinical", "trials", "with", "pioglitazone", "(19", "cases", "from", "12506", "patients,", "0.15%)", "than", "in", "control", "groups", "(7", "cases", "from", "10212", "patients,", "0:07%)", "HR", "2.64", "(95%", "CI", "1.11-6.31,", "P", "0:029).", "After", "excluding", "patients", "in", "whom", "exposure", "to", "study", "drug", "was", "less", "than", "one", "year", "at", "the", "time", "of", "diagnosis", "of", "bladder", "cancer,", "there", "were", "7", "cases", "(0.06%)", "on", "pioglitazone", "and", "2", "cases", "(0.02%)", "in", "control", "groups.", "Available", "epidemiological", "\"data", "also", "suggest", "a", "small", "increased", "risk", "of", "bladder", "cancer", "in", "diabetic", "patients", "treated", "with", "pioglitazone,", "in", "particular", "in", "patients", "treated", "for", "the", "longest", "durations", "and", "with", "the", "highest", "cumulative", "doses.", "A", "possible", "risk", "after", "short", "term", "treatment", "cannot", "be", "excluded.", "Risk", "factors", "for", "bladder", "cancer", "should", "be", "assessed", "before", "initiating", "pioglitazone", "treatment", "(risks", "include", "age,", "smoking", "history,", "exposure", "to", "some", "occupational", "or", "chemotherapy", "agents", "e.g", "cyclophosphamide", "or", "prior", "radiation", "treatment", "in", "the", "pelvic", "region).", "Any", "macroscopic", "haematuria", "should", "be", "investigated", "before", "starting", "pioglitazone", "therapy.", "Patients", "should", "be", "advised", "to", "promptly", "seek", "the", "attention", "of", "their", "physician", "if", "macroscopic", "haematuria", "or", "other", "symptoms", "such", "as", "dysuria", "or", "urinary", "urgency", "develop", "during", "treatment.", "Section", "4.8", "-", "Undesirable", "effects\"", "Inclusion", "of", "bladder", "cancer", "as", "an", "uncommon", "adverse", "reaction", "List", "of", "revisions", "to", "the", "Patient", "Information", "Leaflet", "Section", "1", "-", "What", "Actos/Competact", "is", "and", "what", "it", "is", "used", "for", "It", "is", "an", "anti-diabetic", "medicine", "used", "to", "treat", "type", "2", "(non-insulin", "dependent)", "diabetes", "mellitus,", "when", "metformin", "is", "not", "suitable", "or", "has", "failed", "to", "work", "adequately.", "Your", "doctor", "will", "check", "whether", "Actos/Competact", "is", "working", "3", "to", "6", "months", "after", "you", "start", "taking", "it.", "Actos", "may", "be", "used", "on", "its", "own", "in", "patients", "who", "are", "unable", "to", "take", "metformin,", "and", "where", "treatment", "with", "diet", "and", "exercise", "has", "failed", "to", "control", "blood", "sugar", "or", "may", "be", "added", "to", "other", "therapies", "(such", "as", "metformin,", "sulphonylurea", "or", "insulin)", "which", "have", "failed", "to", "provide", "sufficient", "control", "of", "blood", "sugar.", "Section", "2", "-", "Before", "you", "take", "Actos/Competact", "Do", "not", "take", "Actos/Competact", "if", "you", "have", "or", "have", "ever", "had", "bladder", "cancer.", "if", "you", "have", "blood", "in", "your", "urine", "that", "your", "doctor", "has", "not", "checked", "Section", "4", "-", "Possible", "side", "effects", "Heart", "failure", "has", "been", "experienced", "commonly", "(", "1", "to", "10", "users", "in", "100)", "in", "patients", "taking", "Actos", "in", "combination", "with", "insulin.", "Symptoms", "are", "unusual", "shortness", "of", "breath", "or", "rapid", "increase", "in", "weight", "or", "localised", "swelling", "(oedema).", "If", "you", "experience", "any", "of", "these,", "especially", "if", "you", "are", "over", "the", "age", "of", "65,", "seek", "medical", "advice", "straight", "away.", "Bladder", "cancer", "has", "been", "experienced", "uncommonly", "(I", "to", "10", "users", "in", "1000)", "in", "patients", "taking", "Actos/Competact:", "Signs", "and", "symptoms", "include", "blood", "in", "your", "urine,", "pain", "when", "urinating", "or", "a", "sudden", "need", "to", "urinate", "If", "you", "experience", "any", "of", "these,", "talk", "to", "your", "doctor", "as", "soon", "as", "possible", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-TYNANJ-00213202MAYAN", "Source:", "https://www.indup54dacooogsts.ucsf.edu/docs/psjf0226" ]

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[ "FROM", "HERETAN", "DEMAS", "FAX05-6204-2943", "19994", "18218", "(*)", "21", "31/21", ":", "28/x56:480:", "941295", "F", "1", "Takeda", "Chemical", "Industries,", "Ltd.", "Takeda", "Product", "Planning", "&", "Management", "Dept.,", "International", "Division", "1-1", "Doshomachi", "4-chome,", "Chuo-Ku,", "Osaka", "541,", "JAPAN", "Tel:", "+81", "6", "(204)", "2852", "Fax:", "+81", "6", "(204)", "2943", "TELEFAX", "MESSAGE", "To:", "E.", "Lilly", "&", "Company", "Date:", "January", "21,", "1999", "Att:", "Mr.", "Larry", "Ellingson", "From:", "Kunio", "Iwatani", "Executive", "Director", "Actos", "Product", "Team", "CC:", "Mr.", "Hamanaka,", "TPA", "Subject:", "Upjohn", "Matter", "Dear", "Mr.", "Ellingson,", "Enclosed", "please", "find", "a", "copy", "of", "Upjohn's", "letter", "to", "US", "FDA", "dated", "January", "7,", "1994.", "In", "the", "letter", "Upjohn", "said", "that", "in", "preliminary", "clinical", "evaluation", "in", "the", "United", "States,", "pioglitazone", "did", "not", "satisfy", "Upjohn's", "internal", "requirement", "for", "reduction", "blood", "glucose;", "therefore,", "the", "considerable", "programs", "required", "for", "development", "of", "pioglitazone", "are", "not", "in", "line", "with", "Upjohn's", "business", "needs.", "-..", "They", "did", "not", "mention", "about", "safety", "of", "pioglitazone.", "After", "Upjohn's", "decision,", "Takeda", "approached", "FDA", "and", "consulted", "whether", "Takeda", "might", "go", "further", "the", "clinical", "development", "works", "on", "pioglitazone.", "Since", "the", "FDA's", "response", "was", "positive", "to", "go", "ahead,", "Takeda", "took", "over", "Upjohn's", "works", "and", "finally", "filed", "NDA", "on", "January", "15,", "1999.", "This", "is", "the", "story", "of", "the", "fact.", "Although", "there", "may", "be", "rumors", "about", "the", "reasons", "of", "Upjohn's", "abandonment", "of", "pioglitazone", "development,", "specially", "from", "the", "viewpoints", "of", "safety", "issues,", "it", "might", "be", "advisable", "for", "us", "to", "keep", "saying", "that", "Upjohn's", "decision", "is", "based", "on", "JAN", "21", "'99", "07:43", "DALY", "19", "06", "6204", "2943", "PAGE", ".", "01", "Confidential", "-", "Subject", "to", "Protective", "Order", "LLY-CRCARCH-00003000", "Source:", "https://www.indupbodsfoodonts.ucsf.edu/docs/nljf0226" ]

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[ "DEPARTMENT", "OF", "HEALTH", "&", "HUMAN", "SERVICES", "Public", "Health", "Service", "Food", "and", "Drug", "Administration", "Rockville,", "MD", "20857", "IND", "33,729", "RECEIVED", "REGULATORY", "AFFAIRS", "DEPARTMENT", "Takeda", "Pharmaceuticals", "North", "America,", "Inc.", "Attention:", "Janet", "L.", "Haskin", "JUN", "1", "6", "2003", "Manager,", "Regulatory", "Affairs", "475", "Half", "Day", "Road,", "Suite", "500", "Takeda", "Pharmaceuticals", "North", "America,", "Ins", "Lincolnshire,", "IL", "60069", "Dear", "Ms.", "Haskins:", "Please", "refer", "to", "your", "Investigational", "New", "Drug", "Application", "(IND)", "submitted", "January", "15,", "1999,", "under", "section", "505(i)", "of", "the", "Federal", "Food,", "Drug,", "and", "Cosmetic", "Act", "for", "Actos", "(pioglitazone", "HCI)", "Tablets,", "15", "mg,", "30", "mg", "and", "45", "mg", "We", "also", "refer", "to", "your", "amendment", "dated", "May", "8,", "2003", "(serial", "#", "525),", "received", "on", "May", "9,", "2003,", "that", "provided", "a", "response", "to", "our", "November", "13,", "2002,", "letter", "which", "cited", "the", "reasons", "this", "protocol", "was", "placed", "on", "clinical", "hold", "and", "the", "information", "needed", "to", "resolve", "the", "clinical", "hold", "issues.", "We", "have", "completed", "the", "review", "of", "your", "submission", "and", "have", "concluded", "that", "removal", "of", "the", "clinical", "hold", "is", "not", "warranted.", "We", "acknowledge", "your", "agreement", "to", "monitor", "for", "bladder", "tumors", "in", "your", "clinical", "studies,", "and", "to", "amend", "the", "label", "and", "consent", "documents.", "However,", "until", "further", "information", "on", "bladder", "effects", "from", "ongoing", "studies", "is", "available,", "we", "do", "not", "believe", "studies", "in", "pediatric", "patients", "are", "warranted.", "Until", "you", "have", "submitted", "the", "required", "information", "and", "we", "notify", "you", "that", "you", "may", "initiate", "trials,", "this", "IND", "remains", "on", "clinical", "hold", "and", "you", "may", "not", "legally", "conduct", "clinical", "studies", "under", "it.", "Please", "identify", "your", "response", "to", "the", "clinical", "hold", "issues", "as", "a", "\"CLINICAL", "HOLD", "COMPLETE", "RESPONSE.\"", "To", "facilitate", "a", "response", "to", "your", "submission,", "submit", "this", "information", "in", "triplicate", "to", "the", "IND.", "In", "addition,", "send", "a", "copy", "of", "the", "cover", "letter", "to", "Ms.", "Jena", "Weber.", "Following", "receipt", "of", "your", "complete", "response", "to", "these", "issues,", "we", "will", "notify", "you", "of", "our", "decision", "within", "30", "days.", "424", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-INDNDA-01577085", "in", "MDL", "on", "01/31/13", "Source:", "https://www.induptrygg-ooooits.ucsf.edu/docs/xyjf0226" ]

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[ "DEPARTMENT", "OF", "HEALTH", "&", "HUMAN", "SERVICES", "Public", "Health", "Service", "Food", "and", "Drug", "Administration", "Rockville,", "MD", "20857", "IND", "33,729", "RECEIVED", "REGULATORY", "AFFAIRS", "DEPARTMENT", "Takeda", "Pharmaceuticals", "North", "America,", "Inc.", "Attention:", "Janet", "L.", "Haskin", "JUN", "1", "6", "2003", "Manager,", "Regulatory", "Affairs", "475", "Half", "Day", "Road,", "Suite", "500", "Takeda", "Pharmaceuticals", "North", "America,", "Ins", "Lincolnshire,", "IL", "60069", "Dear", "Ms.", "Haskins:", "Please", "refer", "to", "your", "Investigational", "New", "Drug", "Application", "(IND)", "submitted", "January", "15,", "1999,", "under", "section", "505(i)", "of", "the", "Federal", "Food,", "Drug,", "and", "Cosmetic", "Act", "for", "Actos", "(pioglitazone", "HCI)", "Tablets,", "15", "mg,", "30", "mg", "and", "45", "mg", "We", "also", "refer", "to", "your", "amendment", "dated", "May", "8,", "2003", "(serial", "#", "525),", "received", "on", "May", "9,", "2003,", "that", "provided", "a", "response", "to", "our", "November", "13,", "2002,", "letter", "which", "cited", "the", "reasons", "this", "protocol", "was", "placed", "on", "clinical", "hold", "and", "the", "information", "needed", "to", "resolve", "the", "clinical", "hold", "issues.", "We", "have", "completed", "the", "review", "of", "your", "submission", "and", "have", "concluded", "that", "removal", "of", "the", "clinical", "hold", "is", "not", "warranted.", "We", "acknowledge", "your", "agreement", "to", "monitor", "for", "bladder", "tumors", "in", "your", "clinical", "studies,", "and", "to", "amend", "the", "label", "and", "consent", "documents.", "However,", "until", "further", "information", "on", "bladder", "effects", "from", "ongoing", "studies", "is", "available,", "we", "do", "not", "believe", "studies", "in", "pediatric", "patients", "are", "warranted.", "Until", "you", "have", "submitted", "the", "required", "information", "and", "we", "notify", "you", "that", "you", "may", "initiate", "trials,", "this", "IND", "remains", "on", "clinical", "hold", "and", "you", "may", "not", "legally", "conduct", "clinical", "studies", "under", "it.", "Please", "identify", "your", "response", "to", "the", "clinical", "hold", "issues", "as", "a", "\"CLINICAL", "HOLD", "COMPLETE", "RESPONSE.\"", "To", "facilitate", "a", "response", "to", "your", "submission,", "submit", "this", "information", "in", "triplicate", "to", "the", "IND.", "In", "addition,", "send", "a", "copy", "of", "the", "cover", "letter", "to", "Ms.", "Jena", "Weber.", "Following", "receipt", "of", "your", "complete", "response", "to", "these", "issues,", "we", "will", "notify", "you", "of", "our", "decision", "within", "30", "days.", "424", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-INDNDA-01577085", "in", "MDL", "on", "01/31/13", "Source:", "https://www.induptrygg-ooooits.ucsf.edu/docs/xyjf0226" ]

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[ "DEPARTMENT", "OF", "HEALTH", "&", "HUMAN", "SERVICES", "Public", "Health", "Service", "Food", "and", "Drug", "Administration", "Rockville,", "MD", "20857", "IND", "33,729", "RECEIVED", "REGULATORY", "AFFAIRS", "DEPARTMENT", "Takeda", "Pharmaceuticals", "North", "America,", "Inc.", "Attention:", "Janet", "L.", "Haskin", "JUN", "1", "6", "2003", "Manager,", "Regulatory", "Affairs", "475", "Half", "Day", "Road,", "Suite", "500", "Takeda", "Pharmaceuticals", "North", "America,", "Ins", "Lincolnshire,", "IL", "60069", "Dear", "Ms.", "Haskins:", "Please", "refer", "to", "your", "Investigational", "New", "Drug", "Application", "(IND)", "submitted", "January", "15,", "1999,", "under", "section", "505(i)", "of", "the", "Federal", "Food,", "Drug,", "and", "Cosmetic", "Act", "for", "Actos", "(pioglitazone", "HCI)", "Tablets,", "15", "mg,", "30", "mg", "and", "45", "mg", "We", "also", "refer", "to", "your", "amendment", "dated", "May", "8,", "2003", "(serial", "#", "525),", "received", "on", "May", "9,", "2003,", "that", "provided", "a", "response", "to", "our", "November", "13,", "2002,", "letter", "which", "cited", "the", "reasons", "this", "protocol", "was", "placed", "on", "clinical", "hold", "and", "the", "information", "needed", "to", "resolve", "the", "clinical", "hold", "issues.", "We", "have", "completed", "the", "review", "of", "your", "submission", "and", "have", "concluded", "that", "removal", "of", "the", "clinical", "hold", "is", "not", "warranted.", "We", "acknowledge", "your", "agreement", "to", "monitor", "for", "bladder", "tumors", "in", "your", "clinical", "studies,", "and", "to", "amend", "the", "label", "and", "consent", "documents.", "However,", "until", "further", "information", "on", "bladder", "effects", "from", "ongoing", "studies", "is", "available,", "we", "do", "not", "believe", "studies", "in", "pediatric", "patients", "are", "warranted.", "Until", "you", "have", "submitted", "the", "required", "information", "and", "we", "notify", "you", "that", "you", "may", "initiate", "trials,", "this", "IND", "remains", "on", "clinical", "hold", "and", "you", "may", "not", "legally", "conduct", "clinical", "studies", "under", "it.", "Please", "identify", "your", "response", "to", "the", "clinical", "hold", "issues", "as", "a", "\"CLINICAL", "HOLD", "COMPLETE", "RESPONSE.\"", "To", "facilitate", "a", "response", "to", "your", "submission,", "submit", "this", "information", "in", "triplicate", "to", "the", "IND.", "In", "addition,", "send", "a", "copy", "of", "the", "cover", "letter", "to", "Ms.", "Jena", "Weber.", "Following", "receipt", "of", "your", "complete", "response", "to", "these", "issues,", "we", "will", "notify", "you", "of", "our", "decision", "within", "30", "days.", "424", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-INDNDA-01577085", "in", "MDL", "on", "01/31/13", "Source:", "https://www.induptrygg-ooooits.ucsf.edu/docs/xyjf0226" ]

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[ "3.", "Reports", "to", "any", "third", "party,", "including,", "but", "not", "limited", "to,", "RedBook,", "First", "Data", "Bank,", "Blue", "Book,", "Medi-Span,", "or", "other", "price", "reporting", "service,", "regarding", "prices", "for", "TPNA", "products;", "4.", "Communications", "with", "RedBook,", "First", "Data", "Bank,", "Blue", "Book,", "Medi-Span,", "or", "other", "pricing", "reporting", "services,", "regarding", "prices", "for", "TPNA", "products;", "5.", "WAC", "and", "AWP", "generally;", "6.", "Medicare", "and", "Medicaid", "reimbursement", "for", "TPNA", "pharmaceutical", "products", "generally;", "7.", "Calculation", "and", "reporting", "of", "Average", "Manufacturer", "Price", "and", "Best", "Price", "for", "TPNA", "products,", "as", "may", "be", "required", "by", "federal", "and", "state", "laws", "and", "regulations;", "8.", "Communications", "with", "any", "state", "or", "federal", "governmental", "agency", "regarding", "TPNA's", "participation", "in", "the", "Medicaid", "program;", "9.", "Invoices,", "internal", "sales", "projections,", "and", "profit", "statements", "that", "indicate", "the", "price", "TPNA", "paid", "for", "its", "products", "and", "the", "profits", "IPNA", "made", "based", "upon", "sales", "of", "these", "products;", "10.", "Meetings", "at", "which", "sales,", "marketing,", "and", "pricing", "decisions", "were", "discussed;", "11.", "Communications", "with", "providers,", "if", "any,", "relating", "to", "the", "use", "of", "the", "terms", "\"spread\"", "or", "\"profit\"", "in", "the", "context", "of", "the", "sale", "or", "marketing", "of", "TPNA", "products;", "12.", "Marketing", "materials", "(including", "proposed", "materials),", "if", "any,", "relating", "to", "the", "cost", "and", "\"spread\"", "for", "TPNA", "products;", "13.", "Provision", "of", "free", "samples", "or", "nominally", "priced", "TPNA", "products", "to", "any", "providers;", "and", "14.", "Educational", "grants", "regarding", "TPNA", "products;", "These", "requirements", "are", "related", "to", "all", "TPNA", "marketed", "products.", "Each", "Takeda", "Employee", "or", "Contractor", "shall", "create", "an", "Outlook", "Folder", "entitled", "\"AWP\"", "beneath", "the", "\"Legal", "Hold\"", "folder", "provided", "as", "part", "of", "the", "implementation", "of", "CORP-B-019", "\"E-mail", "Management", "and", "Retention.\"", "Contact", "the", "Help", "Desk", "if", "your", "Outlook", "file", "folder", "structure", "does", "not", "contain", "a", "\"Legal", "Hold\"", "folder.", "This", "means", "that", "all", "documents,", "materials,", "and", "computer", "files", "(including", "e-mails,", "word", "processing", "documents,", "slides,", "etc.)", "falling", "into", "this", "category", "must", "continue", "to", "be", "maintained", "until", "you", "are", "informed", "otherwise,", "regardless", "of", "the", "specified", "record", "retention", "period", "that", "would", "apply", "to", "such", "materials", "under", "Takeda's", "current", "Records", "Retention", "Schedules", "and", "program.", "You", "are", "reminded", "that", "you", "must", "follow", "the", "requirements", "of", "BOP,", "CORP-B-019", "\"E-mail", "Management", "and", "Retention\"", "for", "the", "retention", "of", "electronic", "materials,", "and", "the", "\"Best", "Practices", "For", "The", "Physical", "And", "Electronic", "Storage", "Of", "Materials", "That", "Must", "Be", "Retained", "For", "Legal", "Reasons....\"", "IN", "ALL", "CASES,", "THE", "FOLLOWING", "INSTRUCTIONS", "APPLY", "TO", "DOCUMENTS,", "MATERIALS,", "INFORMATION,", "AND", "THINGS,", "IN", "HARD", "COPY", "OR", "ELECTRONIC", "FORMAT,", "THAT", "ARE", "REQUIRED", "TO", "BE", "RETAINED", "PURSUANT", "TO", "THIS", "LEGAL", "HOLD.", "Last", "printed", "11/30/2012", "4:28:00", "AM", "20122830-042845", "doc", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-RIM30b6-00000665", "Source:", "https://www.indup5316-@0003ts.ucsf.edu/docs/frjf0226" ]

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[ "3.", "Reports", "to", "any", "third", "party,", "including,", "but", "not", "limited", "to,", "RedBook,", "First", "Data", "Bank,", "Blue", "Book,", "Medi-Span,", "or", "other", "price", "reporting", "service,", "regarding", "prices", "for", "TPNA", "products;", "4.", "Communications", "with", "RedBook,", "First", "Data", "Bank,", "Blue", "Book,", "Medi-Span,", "or", "other", "pricing", "reporting", "services,", "regarding", "prices", "for", "TPNA", "products;", "5.", "WAC", "and", "AWP", "generally;", "6.", "Medicare", "and", "Medicaid", "reimbursement", "for", "TPNA", "pharmaceutical", "products", "generally;", "7.", "Calculation", "and", "reporting", "of", "Average", "Manufacturer", "Price", "and", "Best", "Price", "for", "TPNA", "products,", "as", "may", "be", "required", "by", "federal", "and", "state", "laws", "and", "regulations;", "8.", "Communications", "with", "any", "state", "or", "federal", "governmental", "agency", "regarding", "TPNA's", "participation", "in", "the", "Medicaid", "program;", "9.", "Invoices,", "internal", "sales", "projections,", "and", "profit", "statements", "that", "indicate", "the", "price", "TPNA", "paid", "for", "its", "products", "and", "the", "profits", "IPNA", "made", "based", "upon", "sales", "of", "these", "products;", "10.", "Meetings", "at", "which", "sales,", "marketing,", "and", "pricing", "decisions", "were", "discussed;", "11.", "Communications", "with", "providers,", "if", "any,", "relating", "to", "the", "use", "of", "the", "terms", "\"spread\"", "or", "\"profit\"", "in", "the", "context", "of", "the", "sale", "or", "marketing", "of", "TPNA", "products;", "12.", "Marketing", "materials", "(including", "proposed", "materials),", "if", "any,", "relating", "to", "the", "cost", "and", "\"spread\"", "for", "TPNA", "products;", "13.", "Provision", "of", "free", "samples", "or", "nominally", "priced", "TPNA", "products", "to", "any", "providers;", "and", "14.", "Educational", "grants", "regarding", "TPNA", "products;", "These", "requirements", "are", "related", "to", "all", "TPNA", "marketed", "products.", "Each", "Takeda", "Employee", "or", "Contractor", "shall", "create", "an", "Outlook", "Folder", "entitled", "\"AWP\"", "beneath", "the", "\"Legal", "Hold\"", "folder", "provided", "as", "part", "of", "the", "implementation", "of", "CORP-B-019", "\"E-mail", "Management", "and", "Retention.\"", "Contact", "the", "Help", "Desk", "if", "your", "Outlook", "file", "folder", "structure", "does", "not", "contain", "a", "\"Legal", "Hold\"", "folder.", "This", "means", "that", "all", "documents,", "materials,", "and", "computer", "files", "(including", "e-mails,", "word", "processing", "documents,", "slides,", "etc.)", "falling", "into", "this", "category", "must", "continue", "to", "be", "maintained", "until", "you", "are", "informed", "otherwise,", "regardless", "of", "the", "specified", "record", "retention", "period", "that", "would", "apply", "to", "such", "materials", "under", "Takeda's", "current", "Records", "Retention", "Schedules", "and", "program.", "You", "are", "reminded", "that", "you", "must", "follow", "the", "requirements", "of", "BOP,", "CORP-B-019", "\"E-mail", "Management", "and", "Retention\"", "for", "the", "retention", "of", "electronic", "materials,", "and", "the", "\"Best", "Practices", "For", "The", "Physical", "And", "Electronic", "Storage", "Of", "Materials", "That", "Must", "Be", "Retained", "For", "Legal", "Reasons....\"", "IN", "ALL", "CASES,", "THE", "FOLLOWING", "INSTRUCTIONS", "APPLY", "TO", "DOCUMENTS,", "MATERIALS,", "INFORMATION,", "AND", "THINGS,", "IN", "HARD", "COPY", "OR", "ELECTRONIC", "FORMAT,", "THAT", "ARE", "REQUIRED", "TO", "BE", "RETAINED", "PURSUANT", "TO", "THIS", "LEGAL", "HOLD.", "Last", "printed", "11/30/2012", "4:28:00", "AM", "20122830-042845", "doc", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-RIM30b6-00000665", "Source:", "https://www.indup5316-@0003ts.ucsf.edu/docs/frjf0226" ]

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[ "DEPARTMENT", "OF", "HEALTH", "&", "HUMAN", "SERVICES", "Public", "Health", "Service", "Food", "and", "Drug", "Administration", "Rockville,", "MD", "20857", "IND", "33,729", "RECEIVED", "REGULATORY", "AFFAIRS", "DEPARTMENT", "Takeda", "Pharmaceuticals", "North", "America,", "Inc.", "Attention:", "Janet", "L.", "Haskin", "JUN", "1", "6", "2003", "Manager,", "Regulatory", "Affairs", "475", "Half", "Day", "Road,", "Suite", "500", "Takeda", "Pharmaceuticals", "North", "America,", "Ins", "Lincolnshire,", "IL", "60069", "Dear", "Ms.", "Haskins:", "Please", "refer", "to", "your", "Investigational", "New", "Drug", "Application", "(IND)", "submitted", "January", "15,", "1999,", "under", "section", "505(i)", "of", "the", "Federal", "Food,", "Drug,", "and", "Cosmetic", "Act", "for", "Actos", "(pioglitazone", "HCI)", "Tablets,", "15", "mg,", "30", "mg", "and", "45", "mg", "We", "also", "refer", "to", "your", "amendment", "dated", "May", "8,", "2003", "(serial", "#", "525),", "received", "on", "May", "9,", "2003,", "that", "provided", "a", "response", "to", "our", "November", "13,", "2002,", "letter", "which", "cited", "the", "reasons", "this", "protocol", "was", "placed", "on", "clinical", "hold", "and", "the", "information", "needed", "to", "resolve", "the", "clinical", "hold", "issues.", "We", "have", "completed", "the", "review", "of", "your", "submission", "and", "have", "concluded", "that", "removal", "of", "the", "clinical", "hold", "is", "not", "warranted.", "We", "acknowledge", "your", "agreement", "to", "monitor", "for", "bladder", "tumors", "in", "your", "clinical", "studies,", "and", "to", "amend", "the", "label", "and", "consent", "documents.", "However,", "until", "further", "information", "on", "bladder", "effects", "from", "ongoing", "studies", "is", "available,", "we", "do", "not", "believe", "studies", "in", "pediatric", "patients", "are", "warranted.", "Until", "you", "have", "submitted", "the", "required", "information", "and", "we", "notify", "you", "that", "you", "may", "initiate", "trials,", "this", "IND", "remains", "on", "clinical", "hold", "and", "you", "may", "not", "legally", "conduct", "clinical", "studies", "under", "it.", "Please", "identify", "your", "response", "to", "the", "clinical", "hold", "issues", "as", "a", "\"CLINICAL", "HOLD", "COMPLETE", "RESPONSE.\"", "To", "facilitate", "a", "response", "to", "your", "submission,", "submit", "this", "information", "in", "triplicate", "to", "the", "IND.", "In", "addition,", "send", "a", "copy", "of", "the", "cover", "letter", "to", "Ms.", "Jena", "Weber.", "Following", "receipt", "of", "your", "complete", "response", "to", "these", "issues,", "we", "will", "notify", "you", "of", "our", "decision", "within", "30", "days.", "424", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-INDNDA-01577085", "in", "MDL", "on", "01/31/13", "Source:", "https://www.induptrygg-ooooits.ucsf.edu/docs/xyjf0226" ]

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[ "3.", "Reports", "to", "any", "third", "party,", "including,", "but", "not", "limited", "to,", "RedBook,", "First", "Data", "Bank,", "Blue", "Book,", "Medi-Span,", "or", "other", "price", "reporting", "service,", "regarding", "prices", "for", "TPNA", "products;", "4.", "Communications", "with", "RedBook,", "First", "Data", "Bank,", "Blue", "Book,", "Medi-Span,", "or", "other", "pricing", "reporting", "services,", "regarding", "prices", "for", "TPNA", "products;", "5.", "WAC", "and", "AWP", "generally;", "6.", "Medicare", "and", "Medicaid", "reimbursement", "for", "TPNA", "pharmaceutical", "products", "generally;", "7.", "Calculation", "and", "reporting", "of", "Average", "Manufacturer", "Price", "and", "Best", "Price", "for", "TPNA", "products,", "as", "may", "be", "required", "by", "federal", "and", "state", "laws", "and", "regulations;", "8.", "Communications", "with", "any", "state", "or", "federal", "governmental", "agency", "regarding", "TPNA's", "participation", "in", "the", "Medicaid", "program;", "9.", "Invoices,", "internal", "sales", "projections,", "and", "profit", "statements", "that", "indicate", "the", "price", "TPNA", "paid", "for", "its", "products", "and", "the", "profits", "IPNA", "made", "based", "upon", "sales", "of", "these", "products;", "10.", "Meetings", "at", "which", "sales,", "marketing,", "and", "pricing", "decisions", "were", "discussed;", "11.", "Communications", "with", "providers,", "if", "any,", "relating", "to", "the", "use", "of", "the", "terms", "\"spread\"", "or", "\"profit\"", "in", "the", "context", "of", "the", "sale", "or", "marketing", "of", "TPNA", "products;", "12.", "Marketing", "materials", "(including", "proposed", "materials),", "if", "any,", "relating", "to", "the", "cost", "and", "\"spread\"", "for", "TPNA", "products;", "13.", "Provision", "of", "free", "samples", "or", "nominally", "priced", "TPNA", "products", "to", "any", "providers;", "and", "14.", "Educational", "grants", "regarding", "TPNA", "products;", "These", "requirements", "are", "related", "to", "all", "TPNA", "marketed", "products.", "Each", "Takeda", "Employee", "or", "Contractor", "shall", "create", "an", "Outlook", "Folder", "entitled", "\"AWP\"", "beneath", "the", "\"Legal", "Hold\"", "folder", "provided", "as", "part", "of", "the", "implementation", "of", "CORP-B-019", "\"E-mail", "Management", "and", "Retention.\"", "Contact", "the", "Help", "Desk", "if", "your", "Outlook", "file", "folder", "structure", "does", "not", "contain", "a", "\"Legal", "Hold\"", "folder.", "This", "means", "that", "all", "documents,", "materials,", "and", "computer", "files", "(including", "e-mails,", "word", "processing", "documents,", "slides,", "etc.)", "falling", "into", "this", "category", "must", "continue", "to", "be", "maintained", "until", "you", "are", "informed", "otherwise,", "regardless", "of", "the", "specified", "record", "retention", "period", "that", "would", "apply", "to", "such", "materials", "under", "Takeda's", "current", "Records", "Retention", "Schedules", "and", "program.", "You", "are", "reminded", "that", "you", "must", "follow", "the", "requirements", "of", "BOP,", "CORP-B-019", "\"E-mail", "Management", "and", "Retention\"", "for", "the", "retention", "of", "electronic", "materials,", "and", "the", "\"Best", "Practices", "For", "The", "Physical", "And", "Electronic", "Storage", "Of", "Materials", "That", "Must", "Be", "Retained", "For", "Legal", "Reasons....\"", "IN", "ALL", "CASES,", "THE", "FOLLOWING", "INSTRUCTIONS", "APPLY", "TO", "DOCUMENTS,", "MATERIALS,", "INFORMATION,", "AND", "THINGS,", "IN", "HARD", "COPY", "OR", "ELECTRONIC", "FORMAT,", "THAT", "ARE", "REQUIRED", "TO", "BE", "RETAINED", "PURSUANT", "TO", "THIS", "LEGAL", "HOLD.", "Last", "printed", "11/30/2012", "4:28:00", "AM", "20122830-042845", "doc", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-RIM30b6-00000665", "Source:", "https://www.indup5316-@0003ts.ucsf.edu/docs/frjf0226" ]

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[ "From:", "PLK", "RCC1", "Date", "and", "time", "10/27/93", "09", ":", "36:07", "To:", "PJDANIEL-", "-", "PW17", "PO", "PETER", "J.", "DANIELS", "CC:", "RJWELTER-", "-", "PW17", "PO", "RICHARD", "J.", "WELTER", "LTWELCH", "--RCC1", "LAWRENCE", "T", "WELCH", "From:", "plruppel", "subject:", "Pioglitazone", "statement", "Actually,", "this", "statement", "reflects", "pretty", "accurately", "the", "stand", "that", "Jim", "Moe", "and", "Larry", "Olanoff", "presented", "to", "Takeda", "in", "Osaka.", "There", "are", "preclinical", "issues", "and", "the", "amount", "of", "preclinical", "work", "that", "would", "be", "needed", "to", "address", "these", "issues", "and", "the", "modest", "clinical", "efficacy", "that", "has", "been", "seen", "do", "not", "justify", "development", "in", "accordance", "with", "Upjohn's", "business", "needs.", "Larry", "does", "not", "feel", "that", "there", "is", "a", "need", "for", "an", "\"Upjohn", "statement\".", "Please", "let", "me", "know", "if", "you", "want", "to", "discuss", "this", "further.", "Patty", "***", "Forwarding", "note", "from", "PJDANIEL--PW17PO", "10/26/93", "15:44", "*", "*", "*", "From:", "PJDANIEL", "To:", "PLRUPPEL--RCC1", "RUPPEL,", "PATRICIA", "CC", ":", "PJDANIEL", "RJWELTER", "LTWELCH", "-", "-RCC1", "WELCH,", "LAWRENCE", "Subject:", "Pioglitazone", "statement", "Patty,", "thanks", "for", "the", "Takeda", "letter.", "Some", "of", "my", "colleagues", "are", "concerned", "about", "the", "lack", "of", "frankness", "(and", "honesty?)", "of", "the", "Takeda", "statement.", "We", "realise", "we", "are", "hemmed", "in", "by", "a", "confidentiality", "clause,", "but", "does", "this", "have", "the", "endorsement", "of", "our", "senior", "management", ".", "Regards,", "Peter.", "tile", "-", "Takedy", "blogde", "fizone", "license", "ast", "CONFIDENTIAL", "-", "SUBJECT", "TO", "PROTECTIVE", "ORDER", "UPJ-0065604", "Source:", "https://www.indupbydemoodonts.ucsf.edu/docs/sljf0226" ]

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[ "08/07/2002", "18:46", "06", "6204", "2244", "2002", "08/08", "21:49", "FAX", "06", "6204", "2244", "TAKEDA", "DEVELOP", "DIVISION", "41", "003/006", "contact,", "what", "can", "we", "do?", "(7)", "As", "we", "point", "out", "in", "our", "action", "plan", "(see", "Action", "1,", "(1),", "iv),", "we", "can", "claim", "that", "the", "two-stage", "carcinogenicity", "model", "is", "considered", "to", "be", "too", "sensitive", "and", "likely", "to", "result", "in", "false", "positive.", "(8)", "We", "can", "ask", "FDA", "directly", "to", "disclose", "the", "details", "of", "\"promotion", "study\"", "and", "2-year", "carcinogenicity", "studies", "in", "our", "first", "response", "to", "FDA.", "It", "is", "not", "too", "late", "to", "think", "about", "a", "contact", "with", "NN", "after", "FDA's", "response", "to", "our", "first", "comments.", "[Conclusion]", "(1)", "Benefit<", "<Risk", "(2)", "This", "would", "not", "be", "the", "best", "moment", "to", "have", "a", "contact", "with", "NN.", "(3)", "We", "would", "better", "respond", "to", "FDA", "based", "on", "published", "papers,", "our", "data,", "NN's", "official", "comments", "on", "their", "homepage", "and", "the", "information", "that", "FDA", "gave", "TPNA", "about", "NN-622", "and", "pioglitazone", "and", "not", "on", "the", "information", "obtained", "from", "a", "contact", "with", "NN", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-THOMCL-00019746", "Produced", "in", "MDL", "on", "09/14/12", "Source:", "https://www.indupbodocoooosts.ucsf.edu/docs/pljf0226" ]

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[ "8", "January", "2003", "To:", "MPDRAP", "I", "Leader", "cc:", "CEOs", "and", "General", "Managers", "of", "Pharmaceutical", "Units", "My", "Concerns", "about", "sNDA", "for", "Actos", "45mg", "in", "the", "USA", "(Reconfirmation)", "Pharmaceutical", "International", "Division", "Y.", "Narai", "I", "express", "my", "opinion", "about", "the", "conclusion", "drawn", "at", "MPDRAP", "Committee", "Meeting", "where", "it", "was", "agreed", "that", "sNDA", "to", "obtain", "the", "approval", "of", "the", "45mg", "combination", "indications", "would", "be", "submitted,", "as", "well", "as", "the", "safety", "update", "based", "on", "the", "commitment", "studies.", "As", "you", "know,", "Actos", "is", "the", "essential", "product", "for", "IPNA", "and", "is", "vital", "to", "the", "survival", "of", "TPNA.", "If", "unfavorable", "revisions", "in", "the", "Actos", "labeling", "are", "made,", "it", "invites", "the", "serious", "risk", "to", "Actos", "in", "the", "US.", "TPNA", "is", "now", "under", "attack", "from", "GSK,", "especially", "by", "Avandamet", "and", "is", "eager", "to", "maintain", "their", "market", "share.", "In", "addition", "to", "this", "attack,", "if", "the", "indications", "of", "Actos", "are", "reduced,", "TPNA", "is", "pushed", "into", "critical", "situation.", "This", "issue", "seriously", "damages", "not", "only", "US", "market", "but", "also", "Takeda's", "global", "strategy.", "Therefore,", "HQ", "should", "be", "extremely", "cautious", "about", "the", "issues", "related", "to", "Actos.", "If", "this", "sNDA", "raises", "the", "argument", "for", "the", "indications", "of", "Actos,", "for", "example,", "reductions", "in", "the", "indications,", "the", "issues", "will", "come", "to", "a", "critical", "path", "like", "as", "I", "mentioned.", "So", "we", "should", "go", "into", "action", "on", "condition", "that", "there", "is", "no", "such", "risk.", "Combination", "therapy", "in", "the", "US", "market", "accounts", "for", "64%", "of", "total", "Actos", "sales.", "(29%", "in", "combination", "with", "SU,", "27%", "Metformin", "and", "8%", "Insulin)", "Regarding", "the", "possibility", "of", "the", "risk", "of", "labeling", "revision,", "International", "Division", "entrusts", "Development", "Division", "with", "final", "decision.", "However,", "just", "to", "be", "sure,", "I", "would", "like", "to", "reconfirm", "that", "this", "sNDA", "dose", "not", "lead", "to", "a", "serious", "situation.", "I", "heard", "that", "TPNA", "R&D", "suggested", "to", "HQ", "and", "is", "getting", "ready", "for", "sNDA", "for", "the", "45mg", "combination", "indications.", "However,", "HQ", "should", "carefully", "judge", "whether", "this", "sNDA", "should", "be", "submitted", "to", "the", "FDA", "or", "not.", "I", "think", "that", "sNDA", "for", "efficacy", "should", "be", "submitted", "only", "when", "there", "is", "no", "risk", "that", "this", "sND", "A", "damages", "the", "current", "labeling.", "According", "to", "the", "results", "of", "PNFP-343,", "combination", "with", "insulin,", "edema", "was", "observed", "more", "often", "than", "Avandia,", "which", "dose", "not", "have", "the", "indication", "for", "combination", "with", "insulin", "and", "CHF", "in", "this", "study", "seems", "to", "be", "dose", "related.", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-THOMCL-00005583", "Produced", "in", "MDL", "on", "09/14/12", "Source:", "https://www.indupt2290-coots.ucsf.edu/docs/syjf0226" ]

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[ "8", "January", "2003", "To:", "MPDRAP", "I", "Leader", "cc:", "CEOs", "and", "General", "Managers", "of", "Pharmaceutical", "Units", "My", "Concerns", "about", "sNDA", "for", "Actos", "45mg", "in", "the", "USA", "(Reconfirmation)", "Pharmaceutical", "International", "Division", "Y.", "Narai", "I", "express", "my", "opinion", "about", "the", "conclusion", "drawn", "at", "MPDRAP", "Committee", "Meeting", "where", "it", "was", "agreed", "that", "sNDA", "to", "obtain", "the", "approval", "of", "the", "45mg", "combination", "indications", "would", "be", "submitted,", "as", "well", "as", "the", "safety", "update", "based", "on", "the", "commitment", "studies.", "As", "you", "know,", "Actos", "is", "the", "essential", "product", "for", "IPNA", "and", "is", "vital", "to", "the", "survival", "of", "TPNA.", "If", "unfavorable", "revisions", "in", "the", "Actos", "labeling", "are", "made,", "it", "invites", "the", "serious", "risk", "to", "Actos", "in", "the", "US.", "TPNA", "is", "now", "under", "attack", "from", "GSK,", "especially", "by", "Avandamet", "and", "is", "eager", "to", "maintain", "their", "market", "share.", "In", "addition", "to", "this", "attack,", "if", "the", "indications", "of", "Actos", "are", "reduced,", "TPNA", "is", "pushed", "into", "critical", "situation.", "This", "issue", "seriously", "damages", "not", "only", "US", "market", "but", "also", "Takeda's", "global", "strategy.", "Therefore,", "HQ", "should", "be", "extremely", "cautious", "about", "the", "issues", "related", "to", "Actos.", "If", "this", "sNDA", "raises", "the", "argument", "for", "the", "indications", "of", "Actos,", "for", "example,", "reductions", "in", "the", "indications,", "the", "issues", "will", "come", "to", "a", "critical", "path", "like", "as", "I", "mentioned.", "So", "we", "should", "go", "into", "action", "on", "condition", "that", "there", "is", "no", "such", "risk.", "Combination", "therapy", "in", "the", "US", "market", "accounts", "for", "64%", "of", "total", "Actos", "sales.", "(29%", "in", "combination", "with", "SU,", "27%", "Metformin", "and", "8%", "Insulin)", "Regarding", "the", "possibility", "of", "the", "risk", "of", "labeling", "revision,", "International", "Division", "entrusts", "Development", "Division", "with", "final", "decision.", "However,", "just", "to", "be", "sure,", "I", "would", "like", "to", "reconfirm", "that", "this", "sNDA", "dose", "not", "lead", "to", "a", "serious", "situation.", "I", "heard", "that", "TPNA", "R&D", "suggested", "to", "HQ", "and", "is", "getting", "ready", "for", "sNDA", "for", "the", "45mg", "combination", "indications.", "However,", "HQ", "should", "carefully", "judge", "whether", "this", "sNDA", "should", "be", "submitted", "to", "the", "FDA", "or", "not.", "I", "think", "that", "sNDA", "for", "efficacy", "should", "be", "submitted", "only", "when", "there", "is", "no", "risk", "that", "this", "sND", "A", "damages", "the", "current", "labeling.", "According", "to", "the", "results", "of", "PNFP-343,", "combination", "with", "insulin,", "edema", "was", "observed", "more", "often", "than", "Avandia,", "which", "dose", "not", "have", "the", "indication", "for", "combination", "with", "insulin", "and", "CHF", "in", "this", "study", "seems", "to", "be", "dose", "related.", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-THOMCL-00005583", "Produced", "in", "MDL", "on", "09/14/12", "Source:", "https://www.indupt2290-coots.ucsf.edu/docs/syjf0226" ]

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[ "Ms.", "Wakamatsu,", "Assistant", "manager,", "Dept.", "Strategic", "Development,", "et", "al.", "Attachment:", "NDA", "schedule", "for", "each", "project", "approved", "on", "the", "5th", "GDC", "1.", "Openings", "Remarks", "Dr.", "Kitazawa", "made", "opening", "remarks.", "He", "mentioned", "that", "TAKEDA", "has", "been", "driving", "for", "to", "be", "a", "global", "pharmaceutical", "company", "in", "this", "decade,", "concentrating", "all", "resource", "into", "the", "pharmaceutical", "business,", "under", "the", "clear-cut", "leadership", "of", "the", "CEO.", "Pharmaceutical", "Development", "Division", "is", "a", "core", "organization", "of", "Takeda", "Pharmaceutical", "Company,", "enhancing", "the", "pipeline", "products,", "which", "is", "the", "decisive", "factor", "for", "TAKEDA", "business.", "However,", "in", "the", "present", "condition,", "since", "the", "launch", "of", "Actos", "in", "1999", "there", "are", "no", "new", "products", "launched.", "While", "this", "situation", "is", "critical,", "the", "Pharmaceutical", "Development", "Division", "is", "thought", "to", "be", "conservative", "and", "lack", "of", "challenging", "spirit.", "He", "stated", "that", "his", "mission", "is", "to", "improve", "this", "conservative", "atmosphere", "and", "grow", "challenging", "spirit", "to", "develop", "and", "launch", "the", "new", "products", "earlier", "than", "scheduled.", "Formatted:", "Not", "Hidden", "3.", "MPDRAP-I", "(Diabetes)", "1)", "AD-4833", "Update", "of", "US", "status", "by", "TPNA", "Bladder", "tumor", "observed", "in", "NN622", "study", "As", "for", "the", "bladder", "issues,", "an", "expected", "response", "from", "FDA", "is", "in", "early", "October", "and", "pediatric", "study", "(Actos", "508)", "is", "temporarily", "on", "hold,", "however,", "this", "is", "not", "an", "official", "hold.", "In", "the", "recent", "teleconference", "discussing", "non-clinical", "issues,", "the", "experts", "could", "not", "identify", "any", "rational", "hypothesis", "that", "dual", "PPAR", "agonists", "may", "be", "linked", "to", "bladder", "tumogenesis.", "A", "clinical", "expert", "meeting", "is", "scheduled", "for", "October", "1", "and", "2", "to", "discuss", "how", "to", "screen/monitor", "bladder", "tumors", "in", "long-term", "clinical", "trials,", "since", "FDA", "may", "force", "TPNA", "to", "do", "it.", "Label", "changes", "may", "be", "requested", "by", "FDA", "and", "it", "is", "very", "difficult", "to", "assess", "the", "marketing", "impact", "of", "such", "label", "change", "at", "this", "moment.", "It", "was", "suggested", "to", "prepare", "non-clinical", "\"White", "paper\"", "to", "address", "the", "bladder", "issue.", "US", "commitment", "study", "of", "30mg", "vs.", "45mg", "An", "SNDA", "will", "be", "submitted", "in", "this", "autumn,", "where", "studies", "341,", "342,", "343", "and", "513", "are", "included.", "The", "objectives", "of", "the", "submission", "are", "for", "1)", "a", "safety", "purpose,", "not", "for", "an", "efficacy", "or", "new", "indication", "of", "45mg,", "and", "2)", "an", "update", "of", "oral", "contraceptive", "interaction", "results", "in", "the", "label.", "Timelines", "and", "issues", "on", "Actos", "combination", "projects", "were", "presented.", "Actos-Metformin", "Convenience", "Pack", "is", "expected", "to", "file", "sNDA", "in", "March", "2003", "and", "to", "be", "approved", "in", "September", "2003.", "TPNA", "believes", "stability", "data", "of", "3", "months", "are", "sufficient", "2", "Confidential", "-", "Subject", "to", "Protective", "Order", "TAK-THOMCL-00012574", "Source:", "https://www.indupto442coo02ts.ucsf.edu/docs/Imjf0226", "Produced", "in", "MDL", "on", "09/14/12" ]

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