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Apixaban

Phase 3

Deep Vein Thrombosis | Small molecule | Other |Bristol-Myers Squibb Company|Last Updated: Jul 9, 2014

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindACTIVE_CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment8,628
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00452530Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Knee Replacement SurgeryPHASE3 COMPLETED 3,221Jun 1, 2007Jan 1, 2009Jul 9, 2014122 Austria, Belgium +25
NCT00423319Study of an Investigational Drug for the Prevention of Thrombosis-related Events Following Hip Replacement Surgery (ADVANCE-3)PHASE3 COMPLETED 5,407Mar 1, 2007Sep 1, 2009May 14, 2014143 United States, Argentina +19
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Study Endpoints
Primary Endpoints
Rate of Adjudicated Venous Thromboembolic Event-related and All-cause Deaths With Onset During the Intended-treatment Period
Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study drug

Event rate=Number of events divided by the number of patients evaluated. Intended treatment period starts on the day of randomization, and for those who received study drug, ends at the later of 2 days after last dose or 14 days after the first dose of study drug; for randomized patients who did not receive study drug, the period ends 14 days after randomization.Venous thromboembolic event (VTE)=nonfatal pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or asymptomatic proximal DVT detected by ultrasound. VTE-related death=fatal PE or sudden death for which VTE could not be excluded as a cause.

Rate of Composite of Adjudicated Venous Thromboembolic Event (VTE)-Related (Pulmonary Embolism and Symptomatic and Asymptomatic Deep Vein Thrombosis[DVT]) and All-cause Death During the Intended Treatment Period
Day 1 (first dose of study drug) to later of 2 days after last dose or 38 days after first dose

Event rate=Number of events divided by the number of patients evaluated. A mandatory bilateral ascending contrast venogram was to be obtained on Day 35 (± 3). Patients with confirmed symptomatic DVT at any time, or asymptomatic DVT upon venography, were to receive treatment for DVT according to the investigator's standard of care. Signs and symptoms suggestive of VTE included, but were not limited to: 1) lower extremity DVT: erythema, warmth, pain, swelling, tenderness; and 2) PE: pleuritic chest pain, dyspnea, cough, hemoptysis, syncope, light-headedness/dizziness, tachypnea, and tachycardia. Intended Treatment Period started on day of randomization and, for patients who received treatment, ended at the later of 2 days after last dose of study drug or 38 days after the first dose (presurgery) of study drug. For randomized patients who did not receive study drug, the period ended 38 days after randomization.

Secondary Endpoints
Rate of Adjudicated Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism, and Venous Thromboembolic Event-related Death With Onset During the Intended Treatment Period
Day of randomization to later of 2 days after last dose or 14 days after first dose; 14 days after randomization for those who did not receive study
Rate of Major Bleeding, Clinically Relevant Nonmajor Bleeding (CRNM), and Major Bleeding or CRNM
Days 1 to 12
Number of Participants With Serious Adverse Events (SAE), Bleeding Adverse Events (AEs), Discontinuations Due to AEs, and Death as Outcome
Days 1 through 12 + 2 days (nonserious AEs, bleeding AES) or 30 days (SAES, deaths) after last dose of study drug
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Study Design & Arms
AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Apixaban, 2.5 mg BID + PlaceboEXPERIMENTALParticipants received apixaban, 2.5-mg tablets twice daily (BID), plus a matching enoxaparin-placebo injection 12 (±3) hours prior to hip-replacement surgery through 11 (±2) days after the day of surgery.
Enoxaparin, 40 mg QD + PlaceboACTIVE_COMPARATORParticipants received enoxaparin, 40-mg subcutaneous injection once daily (QD), plus a matching apixaban-placebo tablet 12 (±3) hours prior to hip-replacement surgery through 11 (±2) days after the day of surgery.
Apixaban, 2.5 mg BID plus placeboACTIVE_COMPARATORParticipants received apixaban, 2.5 mg twice daily (BID), as oral tablets, and matching enoxaparin-placebo injection once daily (QD)
Enoxaparin, 40 mg QD plus placeboEXPERIMENTALParticipants received enoxaparin, 40 mg QD subcutaneously, and matching apixaban-placebo tablets BID
Interventions
NameTypeDescription
EnoxaparinDRUG40 mg, administered once daily by subcutaneous injection, for 12 days
ApixabanDRUG2.5 mg, administered twice daily as tablets, for 12 days
Enoxaparin-matching placeboDRUGAdministered once daily by subcutaneous injection
Apixaban-matching placeboDRUGOral tablet administered twice daily
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites122

Key Inclusion Criteria * Patients scheduled for either elective unilateral or same-day bilateral total knee replacement surgery (TKR) or a revision of at least 1 component of a TKR * Patients willing and able to undergo bilateral ascending contrast venography Key Exclusion Criteria * Known or sus...

Countries:AustriaBelgiumBrazilChileChinaColombiaCzechiaDenmarkFranceGermanyHungaryIndiaIsraelItalyMalaysiaMexicoNorwayPhilippinesPolandRussiaSingaporeSouth AfricaSouth KoreaSpainSwedenUkraineUnited KingdomUnited StatesArgentinaAustraliaCanadaRomania
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