Open-Lbel Extension of Rndomized, Double-Blind, Plcebo-Controlled, Phse 3 Study of the Sfety nd Anlgesic Efficcy of MNK-795 Oxycodone/Acetminophen Extended-Relese (OC/APAP ER) Tblets in n Acute Pin Model Neil Singl, MD 1 ; Thoms Brrett, PhD 2 ; Lis Sisk 2 ; Kenneth Kostenbder, MD 2 ; Jim Young, PhD 2 1 Lotus Clinicl Reserch LLC, Psden, CA, USA; 2 Mllinckrodt Inc., Hzelwood, MO, USA Introduction uudespite the wide rnge of tretment options vilble for cute pin, dvnces in the mngement of cute pin re needed 1 uumultimodl therpy combining oxycodone (OC) nd cetminophen (APAP) is well-estblished pproch to the tretment of cute pin 2,3 Combining gents with different mechnisms of ction my offer dditive effects, while llowing for the mngement of pin t lower dose of ech component, potentilly reducing the risk of concentrtion-dependent dverse events 4-6 uuin ddition, formultions engineered to provide quick nd sustined relese my offer therpeutic benefit s well s reduce the pill burden 5,7 uumnk-795 (OC/APAP ER) is n extended-relese (ER) combintion OC/APAP nlgesic, nd is being designed to provide both fst onset of nlgesi within 1 hour nd sustined nlgesi over the 12-hour dosing intervl OC/APAP ER tblets employ dul-lyer biphsic delivery mechnism tht, when dministered s single dose (ie, 2 tblets), ensures the immedite-relese component delivers 3.75 mg OC/325 mg APAP nd the ER component delivers 11.25 mg OC/325 mg APAP Incorportes technology designed to provide tmper resistnce nd buse deterrence uuin this pivotl clinicl tril, OC/APAP ER ws studied in n estblished cute pin model in ptients undergoing first mettrsl bunionectomy; mediction effects were evluted 48 hours post-procedure (double-blind) nd continued throughout voluntry open-lbel tretment period (up to 14 dys) Ptients Methods uptients u ged 18 to 75 yers undergoing unilterl, first mettrsl bunionectomy who reported t lest moderte or severe pin intensity nd numeric rting scle score of 4 (out of 1) between the hours of 4: AM nd 12: PM (fter cesstion of intrvenous poplitel nerve block) on the first postopertive dy were eligible for the study Study Design umulticenter, u rndomized, double-blind, plcebo-controlled, prllel group, phse 3 study of OC/APAP ER in ptients with moderte to severe cute pin Screening period of between 2 nd 3 dys before surgery, rndomized double-blind dosing phse of 2 dys (48 h) postprocedure, nd n optionl 14-dy open-lbel extension for qulified ptients (Figure 1) Figure 1: Study Design Surgery completed; b Nerve block stopped; c Erliest strt for pin ssessment nd rndomiztion; d Ltest strt for pin ssessment nd rndomiztion; e Study mediction dministered within 3 minutes of rndomiztion; f Ptients ssessed for prticiption in open-lbel extension within 48 to 52 hours of receiving first dose of study drug; g End-of-tretment evlutions performed within 3 dys of receiving lst dose of study drug; follow-up telephone cll 7±2 dys fter receiving lst dose of study drug (double-blind nd open-lbel phses). uduring u the double-blind phse of the study, ptients were rndomized to receive 2 tblets of OC/APAP ER (totl 15 mg OC/65 mg APAP) or plcebo dministered every 12 hours (, 12, 24, nd 36 h; 4 totl doses) Use of supplementl nlgesi ws permitted (ie, ibuprofen 4 mg up to 6 times per dy [24 mg/d]) during the double-blind nd open-lbel phses of the study ueligibility u criteri for the open-lbel extension phse of the study included completing the double-blind phse of the study; hving pin intensity score 3 t completion of the double-blind phse of the study, but no lter thn 52 hours fter receiving the first dose of study drug; signing n open-lbel extension consent form prior to surgery; nd greeing to prticipte in the open-lbel extension phse of the study uptients u prticipting in the open-lbel phse of the study were dischrged with instructions to tke 2 tblets of OC/APAP ER every 12 hours until no longer needed The open-lbel phse lsted up to 14 dys, with clinic visits t dys 7 nd 14 (±1 dy), followed by telephone cll 7 dys (±2 dys) fter the lst dose uexclusion u criteri included ny medicl condition tht might decrese study complince or lter the bsorption, distribution, metbolism, or excretion of the study drug (eg, severe chronic dirrhe, chronic constiption, irritble bowel syndrome, or unexplined weight loss); gstric bypss surgery or gstric bnd; history of intolernce to short-term opioid use; nd tretment with study drug or bunionectomy in previous 3 months Assessments During the Open-Lbel Extension usfety u nd tolerbility ssessments were conducted throughout the open-lbel phse of the study nd included physicl exmintions, mesurement of vitl signs (eg, sitting blood pressure, pulse rte, nd temperture), nd clinicl lbortory tests (ie, chemistry, hemtology, nd urinlysis) Adverse events were collected t ech visit nd the 7-dy follow-up phone cll uglobl u ssessment of ptient stisfction ws evluted t 48 hours or erly termintion for the blinded-dosing phse nd t every clinic visit for the open-lbel phse Results Ptient Popultion ua utotl of 329 ptients were enrolled nd received 1 dose of study drug in the blinded-dosing phse of the study 166 ptients received OC/APAP ER; 163 received plcebo 293 ptients (89.1%) completed the double-blind phse of the study 146 ptients (49.8%; prior OC/APAP ER, n=77; prior plcebo, n=69) who completed the double-blind phse of the study entered the open-lbel phse of the study, with 129 ptients (88.4%) completing the open-lbel extension 145 ptients ttended the 1-week follow-up visit, nd 36 ptients ttended the 2-week follow-up visit udemogrphic u chrcteristics of the open-lbel sfety popultion were generlly similr between groups (Tble 1) uduring u the open-lbel dosing phse, 12 ptients (82.2%) received ±2% of the expected doses Prmeter Tble 1: Demogrphic nd Bseline Chrcteristics, Open-Lbel Sfety Popultion Plcebo (n=69) All Ptients in Open-Lbel Phse (N=146) Age, y, men (SD) 39.9 (12.4) 41.4 (14.1) 4.6 (13.2) Femle sex, n (%) 67 (87.) 55 (79.7) 122 (83.6) Rce, n (%) White Blck Asin Ntive Hwiin or other Pcific Islnder 42 (54.5) 31 (4.3) 4 (5.2) 48 (69.6) 19 (27.5) 9 (61.6) 5 (34.2) 5 (3.4) 1 (.7) Weight, kg, men (SD) 71.5 (13.1) 73.2 (12.6) 72.3 (12.8) Body mss index, kg/m 2, men (SD) 26. (4.1) 26.6 (3.4) 26.3 (3.8) Sfety nd Tolerbility uduring u the open-lbel phse, 64 ptients (43.8%) experienced 1 TEAE (Tble 2) The most frequently reported TEAEs were primrily gstrointestinl relted (nuse, vomiting, constiption) nd centrl nervous system-relted (somnolence, hedche, dizziness) Tretment-Emergent Adverse Event, n (%) Tble 2: Tretment-Emergent Adverse Events Occurring During the Open-Lbel Phse Plcebo (n=69) All Ptients (N=146) Any TEAE 25 (32.5) 39 (56.5) 64 (43.8) Nuse 8 (1.4) 18 (26.1) 26 (17.8) Vomiting 3 (3.9) 8 (11.6) 11 (7.5) Constiption 4 (5.2) 5 (7.2) 9 (6.2) Somnolence 1 (1.3) 6 (8.7) 7 (4.8) Hedche 4 (5.2) 2 (2.9) 6 (4.1) Dizziness 2 (2.6) 4 (5.8) 6 (4.1) Peripherl edem 3 (3.9) 4 (2.7) Pruritus 1 (1.3) 3 (4.3) 4 (2.7) Infection 1 (1.3) 3 (4.3) 4 (2.7) uvlues u nd chnges in vitl signs fter 7 dys of open-lbel tretment re shown in Tble 3 Vitl signs during the open-lbel phse were norml in >9% of ptients t ny visit During the open-lbel phse, 1.4% of ptients hd shifts from norml to bnorml oxygen sturtion t ny time point Vitl Sign Tble 3: Vitl Sign Mesures nd Chnges From Bseline After 7 Dys of Open-Lbel Tretment Systolic blood pressure, mm Hg Men (SD) Medin Distolic blood pressure, mm Hg Men (SD) Medin Hert rte, bets/min Men (SD) Medin Respirtory rte, breths/min Men (SD) Medin Body temperture, C Men (SD) Medin Oxygen sturtion, % Men (SD) Medin Bseline Vlue (n=146) 117.3 (14.12) 116. 73.2 (9.31) 72. 73.9 (1.81) 74. 16.3 (1.94) 16. 36.66 (.5) 36.7 97.6 (1.69) 98. OL Visit Dy 7 (n=145) 12.6 (14.4) 12. 75.2 (9.7) 74. 74.1 (11.62) 74. 15.8 (1.68) 16. 36.4 (.54) 36.5 98. (1.6) 98. By Dy 14, very few ptients required pin medictions (n=36); therefore, dt from n=145 completing dy 7 re shown here. Ptient Stisfction Chnge From Bseline 3.4 (12.34) 3. 2.1 (8.45) 2..2 (1.99) -1. -.5 (2.52). -.26 (.58) -.2.4 (1.76). uat u the 7-dy follow-up, more thn 88% (of 144 ptients) indicted they were "very stisfied" or "stisfied" on ll mesures (Figure 2) uat u the 14-dy follow-up, more thn 83% (of 36 ptients) indicted they were "very stisfied" or "stisfied" on ll mesures (Figure 2) Ptients (%) 1 Figure 2: Proportion of Ptients Stisfied or Very Stisfied With OC/APAP ER After 7 or 14 Dys of Open-Lbel Phse Tretment 8 6 4 95.1 94.4 91.7 91. 86.1 86.1 9.3 Dy 7 Dy 14 83.3 Conclusions umultiple-dose dministrtion of OC/APAP ER ws generlly well tolerted in this 14-dy open-lbel u extension study The most frequently reported dverse events were consistent with those seen with other opioids in generl, nd specificlly, oxycodone Shifts in lbortory test results, vitl signs, nd oxygen sturtion were generlly smll nd not cliniclly significnt All chnges in clinicl lbortory tests nd vitl signs tht were outside of the defined reference rnge(s) were not cliniclly significnt ccording to the investigtor umore u thn 8% of ptients were very stisfied or stisfied with every mesure of tretment ssessed, including 94.4% for ese of dministrtion, 86.1% for time for the mediction to work, nd 83.3% for level of pin relief uoc/apap u ER is n importnt ddition to the rmmentrium for ptients with moderte to severe cute pin References 1. Apfelbum JL, Chen C, Meht SS, Gn TJ. Postopertive pin experience: results from ntionl survey suggest postopertive pin continues to be undermnged. Anesth Anlg. 23;97(2):534-54. 2. Gmmitoni AR, Gler BS, Lcouture P, et l. Effectiveness nd sfety of new oxycodone/cetminophen formultions with reduced cetminophen for the tretment of low bck pin. Pin Med. 23;4(1):21-3. 3. Cooper SA, Precheur H, Ruch D, et l. Evlution of oxycodone nd cetminophen in tretment of postopertive dentl pin. Orl Surg Orl Med Orl Pthol. 198;5(6):496-51. 4. Brkin RL. Acetminophen, spirin, or ibuprofen in combintion nlgesic products. Am J Ther. 21;8(6):433-442. 5. Rff RB. Phrmcology of orl combintion nlgesics: rtionl therpy for pin. J Clin Phrm Ther. 21;26(4):257-264. 6. Bever WT, McMilln D. Methodologicl considertions in the evlution of nlgesic combintions: cetminophen (prcetmol) nd hydrocodone in postprtum pin. Br J Clin Phrmcol. 198;1(Suppl 2):215S-223S. 7. McCrberg BH, Brkin RL. Long-cting opioids for chronic pin: phrmcotherpeutic opportunities to enhnce complince, qulity of life, nd nlgesi. Am J Ther. 21;8(3):181-186. Disclosures Dr. Singl received grnts s clinicl investigtor from Mllinckrodt Inc. Dr. Brrett, Ms. Sisk, nd Dr. Young re employees of Mllinckrodt Inc. Dr. Kostenbder is pid consultnt to Mllinckrodt Inc. Acknowledgment Technicl editoril nd medicl writing support for the development of this poster ws provided by Sophie Bolick, PhD, Synchrony Medicl Communictions, LLC, West Chester, PA. Funding for this support ws provided by Mllinckrodt Inc., Hzelwood, MO. Objectives uuevlute the sfety of the dministrtion of multiple doses of OC/APAP ER in ptients with moderte to severe cute pin in n open-lbel extension phse of rndomized, double-blind, plcebo-controlled, phse 3 study Assessed the ptient s stisfction with tretment cross 5 dimensions, such s ese of dministrtion nd level of pin relief, on ctegoricl scle (ie, very stisfied, stisfied, neither stisfied nor disstisfied, disstisfied, or very disstisfied) Sttisticl Anlyses udescriptive u sttistics were summrized for bseline chrcteristics nd globl ssessment of stisfction umediction u dherence nd tretment-emergent dverse events (TEAEs) were summrized using frequencies nd percentges usummry u sttistics for ctul vlues nd chnges from bseline were clculted for the physicl exmintion findings, lbortory test results, vitl signs, nd pulse oximetry, nd shift nlysis exmined ctegoricl chnges from bseline to vrious time points u1 uptient reported 3 severe TEAEs, nd 1 ptient reported serious dverse event (ie, deep vein thrombosis determined by the investigtor to be unrelted to tretment with the study drug) uchnges u from bseline in lbortory vlues (ie, hemtology, serum chemistry, nd urinlysis) were generlly smll nd were similr between tretment groups during double-blind periods nd similr between the double-blind nd open-lbel periods Six ptients (4.1%) hd lnine minotrnsferse nd/or sprtte minotrnsferse 3 times the upper limit of norml vlues t lest once during the study Totl bilirubin remined within the norml reference rnge in ll 6 cses None met Hy's Lw criteri 2 Ese of Administrtion Dosing Frequency Number of Tblets Tken Time for Mediction to Work Level of Pin Relief midwest pin society 213 October 25-26 Chicgo, IL
Introduction uudespite the wide rnge of tretment options vilble for cute pin, dvnces in the mngement of cute pin re needed 1 uumultimodl therpy combining oxycodone (OC) nd cetminophen (APAP) is well-estblished pproch to the tretment of cute pin 2,3 Combining gents with different mechnisms of ction my offer dditive effects, while llowing for the mngement of pin t lower dose of ech component, potentilly reducing the risk of concentrtion-dependent dverse events 4-6 uuin ddition, formultions engineered to provide quick nd sustined relese my offer therpeutic benefit s well s reduce the pill burden 5,7 uumnk-795 (OC/APAP ER) is n extended-relese (ER) combintion OC/APAP nlgesic, nd is being designed to provide both fst onset of nlgesi within 1 hour nd sustined nlgesi over the 12-hour dosing intervl OC/APAP ER tblets employ dul-lyer biphsic delivery mechnism tht, when dministered s single dose (ie, 2 tblets), ensures the immedite-relese component delivers 3.75 mg OC/325 mg APAP nd the ER component delivers 11.25 mg OC/325 mg APAP Incorportes technology designed to provide tmper resistnce nd buse deterrence uuin this pivotl clinicl tril, OC/APAP ER ws studied in n estblished cute pin model in ptients undergoing first mettrsl bunionectomy; mediction effects were evluted 48 hours post-procedure (double-blind) nd continued throughout voluntry open-lbel tretment period (up to 14 dys) Objectives uuevlute the sfety of the dministrtion of multiple doses of OC/APAP ER in ptients with moderte to severe cute pin in n open-lbel extension phse of rndomized, double-blind, plcebo-controlled, phse 3 study
Ptients Methods uptients u ged 18 to 75 yers undergoing unilterl, first mettrsl bunionectomy who reported t lest moderte or severe pin intensity nd numeric rting scle score of 4 (out of 1) between the hours of 4: AM nd 12: PM (fter cesstion of intrvenous poplitel nerve block) on the first postopertive dy were eligible for the study Study Design umulticenter, u rndomized, double-blind, plcebo-controlled, prllel group, phse 3 study of OC/APAP ER in ptients with moderte to severe cute pin Screening period of between 2 nd 3 dys before surgery, rndomized double-blind dosing phse of 2 dys (48 h) postprocedure, nd n optionl 14-dy open-lbel extension for qulified ptients (Figure 1) Figure 1: Study Design Surgery completed; b Nerve block stopped; c Erliest strt for pin ssessment nd rndomiztion; d Ltest strt for pin ssessment nd rndomiztion; e Study mediction dministered within 3 minutes of rndomiztion; f Ptients ssessed for prticiption in open-lbel extension within 48 to 52 hours of receiving first dose of study drug; g End-of-tretment evlutions performed within 3 dys of receiving lst dose of study drug; follow-up telephone cll 7±2 dys fter receiving lst dose of study drug (double-blind nd open-lbel phses). uduring u the double-blind phse of the study, ptients were rndomized to receive 2 tblets of OC/APAP ER (totl 15 mg OC/65 mg APAP) or plcebo dministered every 12 hours (, 12, 24, nd 36 h; 4 totl doses) Use of supplementl nlgesi ws permitted (ie, ibuprofen 4 mg up to 6 times per dy [24 mg/d]) during the double-blind nd open-lbel phses of the study ueligibility u criteri for the open-lbel extension phse of the study included completing the double-blind phse of the study; hving pin intensity score 3 t completion of the double-blind phse of the study, but no lter thn 52 hours fter receiving the first dose of study drug; signing n open-lbel extension consent form prior to surgery; nd greeing to prticipte in the open-lbel extension phse of the study uptients u prticipting in the open-lbel phse of the study were dischrged with instructions to tke 2 tblets of OC/APAP ER every 12 hours until no longer needed The open-lbel phse lsted up to 14 dys, with clinic visits t dys 7 nd 14 (±1 dy), followed by telephone cll 7 dys (±2 dys) fter the lst dose uexclusion u criteri included ny medicl condition tht might decrese study complince or lter the bsorption, distribution, metbolism, or excretion of the study drug (eg, severe chronic dirrhe, chronic constiption, irritble bowel syndrome, or unexplined weight loss); gstric bypss surgery or gstric bnd; history of intolernce to short-term opioid use; nd tretment with study drug or bunionectomy in previous 3 months Assessments During the Open-Lbel Extension usfety u nd tolerbility ssessments were conducted throughout the open-lbel phse of the study nd included physicl exmintions, mesurement of vitl signs (eg, sitting blood pressure, pulse rte, nd temperture), nd clinicl lbortory tests (ie, chemistry, hemtology, nd urinlysis) Adverse events were collected t ech visit nd the 7-dy follow-up phone cll uglobl u ssessment of ptient stisfction ws evluted t 48 hours or erly termintion for the blinded-dosing phse nd t every clinic visit for the open-lbel phse Assessed the ptient s stisfction with tretment cross 5 dimensions, such s ese of dministrtion nd level of pin relief, on ctegoricl scle (ie, very stisfied, stisfied, neither stisfied nor disstisfied, disstisfied, or very disstisfied) Sttisticl Anlyses udescriptive u sttistics were summrized for bseline chrcteristics nd globl ssessment of stisfction umediction u dherence nd tretment-emergent dverse events (TEAEs) were summrized using frequencies nd percentges u usummry sttistics for ctul vlues nd chnges from bseline were clculted for the physicl exmintion findings, lbortory test results, vitl signs, nd pulse oximetry, nd shift nlysis exmined ctegoricl chnges from bseline to vrious time points
Results Ptient Popultion ua utotl of 329 ptients were enrolled nd received 1 dose of study drug in the blinded-dosing phse of the study 166 ptients received OC/APAP ER; 163 received plcebo 293 ptients (89.1%) completed the double-blind phse of the study 146 ptients (49.8%; prior OC/APAP ER, n=77; prior plcebo, n=69) who completed the double-blind phse of the study entered the open-lbel phse of the study, with 129 ptients (88.4%) completing the open-lbel extension 145 ptients ttended the 1-week follow-up visit, nd 36 ptients ttended the 2-week follow-up visit udemogrphic u chrcteristics of the open-lbel sfety popultion were generlly similr between groups (Tble 1) uduring u the open-lbel dosing phse, 12 ptients (82.2%) received ±2% of the expected doses Tble 1: Demogrphic nd Bseline Chrcteristics, Open-Lbel Sfety Popultion Prmeter Plcebo (n=69) All Ptients in Open-Lbel Phse (N=146) Age, y, men (SD) 39.9 (12.4) 41.4 (14.1) 4.6 (13.2) Femle sex, n (%) 67 (87.) 55 (79.7) 122 (83.6) Rce, n (%) White Blck Asin Ntive Hwiin or other Pcific Islnder 42 (54.5) 31 (4.3) 4 (5.2) 48 (69.6) 19 (27.5) 9 (61.6) 5 (34.2) 5 (3.4) 1 (.7) Weight, kg, men (SD) 71.5 (13.1) 73.2 (12.6) 72.3 (12.8) Body mss index, kg/m 2, men (SD) 26. (4.1) 26.6 (3.4) 26.3 (3.8) Sfety nd Tolerbility uduring u the open-lbel phse, 64 ptients (43.8%) experienced 1 TEAE (Tble 2) The most frequently reported TEAEs were primrily gstrointestinl relted (nuse, vomiting, constiption) nd centrl nervous system-relted (somnolence, hedche, dizziness) Tretment-Emergent Adverse Event, n (%) Tble 2: Tretment-Emergent Adverse Events Occurring During the Open-Lbel Phse Plcebo (n=69) All Ptients (N=146) Any TEAE 25 (32.5) 39 (56.5) 64 (43.8) Nuse 8 (1.4) 18 (26.1) 26 (17.8) Vomiting 3 (3.9) 8 (11.6) 11 (7.5) Constiption 4 (5.2) 5 (7.2) 9 (6.2) Somnolence 1 (1.3) 6 (8.7) 7 (4.8) Hedche 4 (5.2) 2 (2.9) 6 (4.1) Dizziness 2 (2.6) 4 (5.8) 6 (4.1) Peripherl edem 3 (3.9) 4 (2.7) Pruritus 1 (1.3) 3 (4.3) 4 (2.7) Infection 1 (1.3) 3 (4.3) 4 (2.7) u1 uptient reported 3 severe TEAEs, nd 1 ptient reported serious dverse event (ie, deep vein thrombosis determined by the investigtor to be unrelted to tretment with the study drug) uchnges u from bseline in lbortory vlues (ie, hemtology, serum chemistry, nd urinlysis) were generlly smll nd were similr between tretment groups during double-blind periods nd similr between the double-blind nd open-lbel periods Six ptients (4.1%) hd lnine minotrnsferse nd/or sprtte minotrnsferse 3 times the upper limit of norml vlues t lest once during the study Totl bilirubin remined within the norml reference rnge in ll 6 cses None met Hy's Lw criteri
uvlues u nd chnges in vitl signs fter 7 dys of open-lbel tretment re shown in Tble 3 Vitl signs during the open-lbel phse were norml in >9% of ptients t ny visit During the open-lbel phse, 1.4% of ptients hd shifts from norml to bnorml oxygen sturtion t ny time point Tble 3: Vitl Sign Mesures nd Chnges From Bseline After 7 Dys of Open-Lbel Tretment Vitl Sign Bseline Vlue (n=146) OL Visit Dy 7 (n=145) Chnge From Bseline Systolic blood pressure, mm Hg Men (SD) Medin 117.3 (14.12) 116. 12.6 (14.4) 12. 3.4 (12.34) 3. Distolic blood pressure, mm Hg Men (SD) Medin 73.2 (9.31) 72. 75.2 (9.7) 74. 2.1 (8.45) 2. Hert rte, bets/min Men (SD) Medin 73.9 (1.81) 74. 74.1 (11.62) 74..2 (1.99) -1. Respirtory rte, breths/min Men (SD) Medin 16.3 (1.94) 16. 15.8 (1.68) 16. -.5 (2.52). Body temperture, C Men (SD) Medin 36.66 (.5) 36.7 36.4 (.54) 36.5 -.26 (.58) -.2 Oxygen sturtion, % Men (SD) Medin 97.6 (1.69) 98. 98. (1.6) 98. By Dy 14, very few ptients required pin medictions (n=36); therefore, dt from n=145 completing dy 7 re shown here..4 (1.76). Ptient Stisfction uat u the 7-dy follow-up, more thn 88% (of 144 ptients) indicted they were "very stisfied" or "stisfied" on ll mesures (Figure 2) uat u the 14-dy follow-up, more thn 83% (of 36 ptients) indicted they were "very stisfied" or "stisfied" on ll mesures (Figure 2) Figure 2: Proportion of Ptients Stisfied or Very Stisfied With OC/APAP ER After 7 or 14 Dys of Open-Lbel Phse Tretment 1 95.1 94.4 91.7 91. 86.1 86.1 9.3 Dy 7 Dy 14 83.3 8 Ptients (%) 6 4 2 Ese of Administrtion Dosing Frequency Number of Tblets Tken Time for Mediction to Work Level of Pin Relief
Conclusions umultiple-dose dministrtion of OC/APAP ER ws generlly well tolerted in this 14-dy open-lbel u extension study The most frequently reported dverse events were consistent with those seen with other opioids in generl, nd specificlly, oxycodone Shifts in lbortory test results, vitl signs, nd oxygen sturtion were generlly smll nd not cliniclly significnt All chnges in clinicl lbortory tests nd vitl signs tht were outside of the defined reference rnge(s) were not cliniclly significnt ccording to the investigtor umore u thn 8% of ptients were very stisfied or stisfied with every mesure of tretment ssessed, including 94.4% for ese of dministrtion, 86.1% for time for the mediction to work, nd 83.3% for level of pin relief uoc/apap u ER is n importnt ddition to the rmmentrium for ptients with moderte to severe cute pin References 1. Apfelbum JL, Chen C, Meht SS, Gn TJ. Postopertive pin experience: results from ntionl survey suggest postopertive pin continues to be undermnged. Anesth Anlg. 23;97(2):534-54. 2. Gmmitoni AR, Gler BS, Lcouture P, et l. Effectiveness nd sfety of new oxycodone/cetminophen formultions with reduced cetminophen for the tretment of low bck pin. Pin Med. 23;4(1):21-3. 3. Cooper SA, Precheur H, Ruch D, et l. Evlution of oxycodone nd cetminophen in tretment of postopertive dentl pin. Orl Surg Orl Med Orl Pthol. 198;5(6):496-51. 4. Brkin RL. Acetminophen, spirin, or ibuprofen in combintion nlgesic products. Am J Ther. 21;8(6):433-442. 5. Rff RB. Phrmcology of orl combintion nlgesics: rtionl therpy for pin. J Clin Phrm Ther. 21;26(4):257-264. 6. Bever WT, McMilln D. Methodologicl considertions in the evlution of nlgesic combintions: cetminophen (prcetmol) nd hydrocodone in postprtum pin. Br J Clin Phrmcol. 198;1(Suppl 2):215S-223S. 7. McCrberg BH, Brkin RL. Long-cting opioids for chronic pin: phrmcotherpeutic opportunities to enhnce complince, qulity of life, nd nlgesi. Am J Ther. 21;8(3):181-186. Disclosures Dr. Singl received grnts s clinicl investigtor from Mllinckrodt Inc. Dr. Brrett, Ms. Sisk, nd Dr. Young re employees of Mllinckrodt Inc. Dr. Kostenbder is pid consultnt to Mllinckrodt Inc. Acknowledgment Technicl editoril nd medicl writing support for the development of this poster ws provided by Sophie Bolick, PhD, Synchrony Medicl Communictions, LLC, West Chester, PA. Funding for this support ws provided by Mllinckrodt Inc., Hzelwood, MO.