Combined use of calcipotriol solution (SOp.g/ ml) and Polytar liquid in scalp psoriasis.

Transcription

1 MCS9506INT 27 April1999 Pag 11 of 189 Summary This documnt has bn dov.;nloadd from \v\vw.lo-pharma.com subjct to th trms of us stat on th wbsit. It contains data and rsults rgarding approvd and non-approvd uss, formulations or tratmnt rgimns, and it is providd for transparncy and informational purposs only. Th contnt dos not rflct th oomplt rsults from all studi.s rlatd to a product. As a documnt of scijltific natur it is not to b sn as a rcommndation or advic rgarding th us of any products and you must always consult th spcific prscribing information approvd for th product prior to any prscription or us. MCS9506 INT Combind us of calcipotriol solution (SOp.g/ ml) and Polytar liquid in scalp psoriasis. A prospctiv, multicntr, opn-labl, randomisd, paralll group comparison of calcipotriol ~oh~tion usd with Polytal" liquid and calcipotriol solution alon for ight wks. Study Objctivs To compar th fficacy, safty and tolrability of calcipotriol solution (50"1-lg/ ml) whn usd alon and whn usd togthr with a tar basd tratmnt (Polytar liquid) in scalp psoriasis. Th primary rspons critrion was basd on th invstigators' ovrall assssmnt of tratmnt rspons on th scalp. Study Dsign A prospctiv, multicntr, opn-labl, randomisd, paralll group comparison for ight wks. At visit l all patints rcivd tratmnt with calcipotriol solution (SOp.g/ ml) applid twic daily to th scalp. In addition, patints wr randomly assignd to opn tratmnt with ithr Polytar liquid usd twic wkly or a non-mdicatd shampoo Gohnson's Baby Shampoo~) usd twic wkly. Patints wr sn aftr 2, 4 and 8 wks tratmnt (visits 2, 3 and 4). H th scalp psoriasis was judgd as 'clard' according to th invstigators' ovrall assssmnt of tratmnt rspons prior to visit 4, patints lft th study at that tim.

2 Pag 12 of April1999 MCS9506INT Patints to b ntrd Four hundrd and fifty patints from gnral practic wr to b randomisd. Th main inclusion critria wr : a clinical diagnosis of mild to modrat scalp psoriasis with prsnt or prvious chronic plaqu psoriasis on th body; at last 18 yars of ag; fmals of child-baring potntial to b using adquat contracption. Th main xclusion critria wr : acut guttat, pustular or ry.throdrmic psoriasis; tratmnt with topical antipsoriatic agnts on th scalp, systmic antipsoriatic agnts, PUV A, UVB, >400iu vitamin D daily, calcium tablts, >5000iu vitamin A daily, or any othr mdication which might affct th study disas; hyprsnsitivity to study mdications; prgnancy or brast fding; hyprcalcamia; significant rnal or hpatic disas. Study Procdurs Invstigators' assssmnts wr: xtnt of scalp psoriasis scord as 0 (no involvmnt), 1 (1-19%), 2 (20-39%), 3 (40-59%), 4 (60-79%) or 5 (80-100%); svrity of rdnss, thicknss and scalinss of scalp psoriasis sparatly scord as O=absnt, 1 =slight, 2=modrat, 3=svr, 4=svrst possibl, and a total sign scor was calculatd as th sum of th scors for all thr signs; ovrall assssmnt of tratmnt rspons compard to visit 1 as wors, no. chang, slight improvmnt, modrat improvmnt, markd improvmnt or clard Patints' assssmnts wr: svrity of thir scalp psoriasis, svrity of itching and skin flaking on th scalp sparatly scord as absnt, mild, modrat or svr; ovrall assssmnt of rspons to, and accptability of, tratmnt sparatly scord as vry poor, poor, avrag, good or xcllnt; quality of lif using a drmatology lif quality indx (DLQI) and burdn of disas qustionnair. For th DLQI, th possibl rang of th scor was 0 to 30 (th highr th scor, th gratr th impairmnt of quality of lif).

3 MCS9506INT 27 April1999 Pag 13 of 189 Advrs vnts wr rcordd and laboratory assssmnts, including srum calcium, wr masurd. Schdul of study procdurs: Visit Wk Informd consnt * Mdical history... Randomisation... Invstigators' assssmnts: 1) Ovrall assssmnt of rspons ) Extnt/ clinical signs of scalp psoriasis... Patints' assssmnts: 1) clinical symptoms 2) ovrall assssmnt of tratmnt 3) quality of lif * * * * * (1) Advrs vnts * * * Laboratory assssmnts * * (1) Supply of tst mdication... * * Collction of tst mdication * * (t l Or at tim of withdrawal from study Rspons Critria Th primary rspons critrion was th proportion of patints in ach tratmnt group who achivd ' markd improvmnt' or 'claranc' (tratmnt succss) of scalp psoriasis according to th invstigators' ovrall assssmnt of tratmnt rspons at th nd of tratmnt. Scondary rspons critria wr basd on : th invstigators' assssmnt of xtnt of scalp psoriasis and clinical signs of scalp psoriasis; patints'

4 Pag 14 of April1999 MCS9506INT assssmnt of clinical symptoms, ovrall assssmnt of tratmnt rspons and accptability, and quality of lif; advrs vnts and laboratory assssmnts. Study Population Rsults A total of 461 patints wr rcruitd and randomisd, 236 to calcipotriol solution plus Polytar liquid, 225 to calcipotriol solution plus non-mdicatd shampoo. 186 (79%) patints randomisd to Polytar liquid attndd th last study visit (visit 4), or compltd th study bfor this visit as thir scalp psoriasis had clard, compard to 179 (80%) in th non-mdicatd shampoo group. Baslin Data Th two tratmnt groups wr wll matchd in trms of dmographics and baslin disas charactristics, as shown blow. Polytar Liquid Non-mdicatd Shampoo Man ag (yars) Fmals(%) Caucasians (%) Man duration of scalp psoriasis (yars) Man sign scors Thicknss Rdnss Scali nss Total Man scor for 'xtnt' Man scor for DLQI

5 MCS9506INT 27 April1999 Pag 15 of 189 Efficacy Rsults Invstigators' assssmnts Ovrall assssmnt of tratmnt rspons : in th pr-protocol population, th numbr of patints with 'trabnnt succss' at nd of tratmnt was 118 (55.9%) in th Polytar liquid group compard to 107 (51.7%) in th nonmdicatd shampoo group. Th diffrnc btwn th groups was not statistically significant (P=0.388; odds ratio for th comparison of Polytar liqul.d r""lativ"" to non mdt'catd sl.. - -~ ~~ oc:a~ rt t~ - _... _--a.:-.c. _.:...:.. - uco..u yvv- ~d J I U '-~ JVJ uuu;:. Jc:IIU.V JlVIII 0.81 to 1.75). Th rsults for thm population wr similar. Tim to first achiv an assssmnt of 'tratmnt succss' : thr wr no statistically significant diffrncs btwn th tratmnt groups (P=0.648 for pr-protocol population, P=0.798 for ITT population). Total sign scor : th man dcras from baslin to nd of tratmnt was 3.3 in th Polytar 431 liquid group compard to 2.8 in th non-mdicatd shampoo group, and th diffrnc btwn th groups was statistically significant (P=0.040; man diffrnc = 0.43; 95% Cl from 0.02 to 0.84). Individual sign scors : th man dcrass from basjin to th nd of tratmnt ar shown blow. Polytar Non-mdicatd Diffrnc btwn tratmnt groups Liquid Shampoo Diffrnc (95% Cl) P-valu Thicknss (-0.07 to 0.26) Rdnss (-0.05 to 0.28) Scalinss (0.04 to 0.39) Extnt of scalp psoriasis : th man dcras from baslin to nd of trabnnt in th scor was 1.0 in th Polytar liquid group, compard to 0.9

6 Pag 16 of April1999 MCS9506INT in th non-mdicatd shampoo group, and th diffrnc btwn th groups was not statistically significant (P=0.123; man diffrnc= 0.17; 95% CI from to 0.39). Patints' assssmnts Symptoms : th odds ratios for th odds of improvmnt in th Polytar liquid group rlativ to that in th non-mdicatd shampoo group at th nd of tratmnt ar shown blow. Odds ratio (95% Cl) P-valu Svrity 1.44 (0.99 to 2.11) Itching 1.49 (1.04 to 2.15) Skin flaking 1.25 (0.87 to 1.78) In all cass, th odds ratio is in favour of th Polytar liquid group Patints' assssmnt of tratmnt : th prcntags of patints scoring 'good' or 'xcllnt' at th nd of tratmnt ar givn blow. Poly tar Non-mdicatd Odds ratio t ) (95% Cl) P-valu Liqu:id Shampoo (N=211) (N=207) Rspons to (0.96 to 2.29) tratmnt Accptability of (0.78 to 1.99) tratmnt t ) Odds ratio for comparison of Polytar liquid rlativ to non-mdicatd shampoo. Quality of lif : thr wr no statistically significant diffrncs btwn tratmnt groups. Th man dcras from baslin to th nd of tratmnt in DLQI scor (a dcras rprsnting an improvmnt in quality of lif)

7 MCS9506INT 27 April1999 Pag 17 of 189 '. was 3.0 in both tratmnt groups (P=0.992; man diffrnc= 0.01; 95% Cl from to 0.97). Safty Rsults Th prcntags of patints rporting advrs vnts and th numbr of vnts rportd ar shown blow. Polytal' Liquid Non-mdicatd Shampoo I ln=??4),-., (N=217) % of No. of % of No. of patints vnts patints vnts All vnts Cutanous vnts on fac on scalp Th numbr and prcntag of advrs vnts rportd of 'svr', 'modrat' and 'mild' svrity, and of 'probabl', 'possibl' and 'unlikly' rlation to study mdication ar shown blow. Polytar Liquid Non-mdicatd Shampoo No. of vnts % No. of vnts % Svrity Svr Modrat Mild Not classifid Rlation to study mdication Probabl Possibl Unlikly

8 Pag 18 of April1999 MCS9506INT Eightn (7.6%) patints randomisd to Polytar liquid and 19 (8.4%) patin~ randomisd to non-mdicatd shampoo withdrw du to unaccptabl advrs vnts. Four patints in ach group suffrd srious advrs vnts, all of 'unlikly' rlation to study mdication. For all laboratory paramtrs tstd, th man chang from baslin to nd of trabnnt was small, and was similar in th two tratmnt groups. Thr patints in th Polytar liquid group and svn patin~ in th non-mdicatd shampoo group had significantly abnormal laboratory valus at th nd of th study. Ths valus wr ou~id th normal rfrnc rang at th start of th study, xcpt in two patints in th non-mdicatd shampoo group: in on of ths th abnormalitis wr considrd to b of unlikly rlation to th study tratmnt by th invstigator, and in th scond th abnormality was considrd to b not clinically significant by th invstigator. Conclusions In trms of th primary fficacy critrion, thr was no statistically significant diffrnc btwn th calcipotriol solution/polytar liquid group and th calcipotriol solution/non-mdicatd shampoo group. Howvr thr wr som statistically significant diffrncs in th scondary fficacy critria in favour of th calcipotriol solution/polytar liquid tratmnt Us of Polytar liquid with calcipotriol solution in th trabnnt of scalp psoriasis is wlltolratd, with no incras in advrs vnts. Calcipotriol solution in combination with Polytar liquid is wll tolratd in th tratmnt of scalp psoriasis with som vidnc of nhancd fficacy.