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MC 890 - CSR

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CLINICAL STUDY REPORT

INVESTIGATION ON THE ACCEPTABILITY

OF CALCIPOTRIOL SOLUTION IN PATIENTS

WITH PSORIASIS OF THE SCALP

An Open, Single-Center, Pilot Study

The clinical study report has been redacte.d using the following principles: Where necessary ,information is anonymised to protect the privacy of study subjects. and named p ers.ons as.s.o ciate d \Vith the-trial as well as. to retain commercial confidential information. Swnmazy data are included but data onindividuals.tudy subjects, including data listings., are removed. This may result in page numbers not being consecutively numbered. Access to anonymised dataon individu alstudy subj ectmay be obtained upon approval ofa research proposal by the Patient and Scientific Review Board. Appendices to the clinical study report are omitted. Furth er de-tails and principles for anonymisation is available in the- do c:ument LEO PH.ARIVLI\ PRINCIPLES FOR ANONYMlSAJION OF CLINICAL TRIAL DATA

MC 890 STUDY

Medical Department

Leo Pharmaceutical Products

Denmark 00147189

10 March, 1993

MC 890 Shtdy Page 1

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Page 2 MC 890 Study

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MC 890 Study Page 3

ABSTRACT

The acceptability and tolerability of calcipotriol solution was evaluated in an open, single center

study. Patients with mild to moderate scalp psoriasis (and with concurrent psoriatic lesions on

the body) were recruited at one center in the United Kingdom. Patients received caldpotriol

solution (50 J,Lg/ ml) applied twice daily on the scalp without occlusion. A maximum of 60 m1

solution was provided per week. Assessments were made after 2, 4 and 6 weeks.

Eleven patients were included in the study. Five patients withdrew from the study for the

following reasons: Default (3 patients), deterioration of psoriasis (1 patient) and 1 patient

reported that ''the treatment was prunful" and "did not help".

Patient's assessment of the acceptability of caldpotriol solution is shown in the table:

Acceptability of caldpotriol solution

stinging

Burning

Painful

Other

Visit 2 ( n s 10)

,~,.- .. __ ... ': :--

1

0

0.

... :; .t '

Total no. of patients reporting one .or ~ore experiences

5 . ... . 4 .

II Two pa tient s reported both stinging ancf burni ng ~ One pat i e nt reported both atinsing and burnins 31 One patient reported "sc:alp dry" :':"

No serious or unexpected adverse events were reported / observed. No patient became

hypercalcaemic.

Mean total sign score (ie sum of scores for redness, thickness and scaling) decreased from a

mean of 8.7 (on a 12-point scale) at start of treatment to 6.0 at end of treatment.

It is concluded that the acceptability, safety and efficacy of twice daily application of caldpotriol

solution (50 J.Lg/ ml) should be further investigated in large, well-controlled studies of patients

with scalp psoriasis.

., ... .. . . . .. ~ ..... ' . . ' . . . .. ...... .... .. .

Page 4

CLINICAL STUDY REPORT APPROVAL

This Clinical Study Report has been approved by:

utical Products DK-2750 Ballerup DENMARK fel.: ext..

MC 890 Study

Signature

Date /95/

MC 890 Study

, REPORT AUTHORS

M.D. ),c .. ">'> rt,.,nn t

Leo Pharmaceutical Products DK-2750 Ballerup DENMARK Tel

M.D. partment

rmaceutical Products DK-2750 Balle rup DENMARK Tel.:

..... -. .......... Department Leo Laboratories Limited Longwick Road Princes Risborough Aylesbury Bucks HP17 9RR UNITED KINGDOM TeL

. . '

PageS

- .. .. . . - -. ~ ._,:. ....... ~ .. -

?age 6 MC 890 Study

MC 890 Study Page 7

, TABLE OF CONTENTS

1

2

3

3.1 3.2

4

5

6

7

7.1 7.2 7.3 7.4 7.5

8

9

Page

ABSTRACT 3

CLINICAL STUDY REPORT APPROVAL . . . . . . . . . . . . . . . . . . . . . . . . 4

REPORT AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

TABLE OF CONTENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

INVESTIGATOR AND STUDY CENTER . . . . . . . . . . . . . . . . . . . . . . . . . 9

COMPANY PERSONNEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

OBJECTIVE OF THE STUDY . ................. . .. ... .. . . .. . .. .

DESIGN OF STUDY . . ... .. . . .. . ... ... .. .. . .. ............. . .

CRITERIA FOR SELECTION OF STUDY PATIENTS ............... .

INCLUSION CRITERIA ............ ... .. . ... ... . .. ...... .. . EXCLUSION CRITERIA ............ . ............... . .. ........ .

CRITERIA FOR EARLY WITHDRAWAL FROM THE STUDY .. .. .. . .

STUDY MEDICATION ... .... .. ... . ... . ... .. .. ........... .. .

CONCOMITANT THERAPY . . .. ............ . . . . . . ... . .. . . . . . .

STUDY PROCEDURES ........... . ...... .. ... . ... . ......... .

MEDICAL HISTORY . .. ....... . ... . .. ... ..... . ...... ..... . .. . ACCEPT ABIUTY ASSESSMENT ... . .... . ........................ CLINICAL ASSESSMENT ........ .. ...... . ... . ... . . . ... . ...... LABORATORY EXAMINATIONS . . .. ... . ... ... . .. . . ... . ... .. .... . RECORDING OF ADVERSE EVENTS . .... . .. .... . ... . .... . . .. .

PRESENTATION OF RESULTS . ... .. ..... .. . .... . . .. ......... .

COMPLIANCE WITH ETHICAL RESPONSIBILITIES

11

11

11

11 12

12

13

14

14

15. 15 15 16 16

17

17

. .. . . : " " .. ; ... . . . ~ .. :_ ... _. ___ ... . . ..

Page 8 MC 890 Study

TABLE OF CONTENTS - cont'd

10

10.1 10.2 10.3 10.4 10.5

10.6 10.7 10.8

11

RESULTS ........ ............ . ..... . . .. . ...... .. ..... .. .. .

STIJDY PERIOD ...... ..... .. . ...... .. . . ....... ... ...... . . .. . STt.JDY POPULATION ..... . .............. .. . .......... . ..... . BASELINE DATA ..... . . .... .... . ............ . ...... ..... .... . ........ . DURATION OF TREATMENT . .. .......... .. ............... .. .. . ACCEPT ABrLITY /TOLERABILITY OF CA LCIPOTRIOL SOLUTION IN SCALP PSORIASIS ..... . . ..................... , . . ... ..... . . EFFECT Of CALCIPOTRIOL SOLUTION ON SCALP PSORIASlS . ..... ..... . CONCOMITANT DRUG TREATMENT ......... . ........... .. ... .. . SAFETY OF CALCIPOTRIOL SOLUTION .. ... ........ . .. . ....... . . .

CONCLUSION .................... . .... ... . . . ..... ... .... .

APPENDIX I: Study Protocol APPENDIX II: Case Record Form

Page

19

19 20 21 24

24 29 32 32

41

-.

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MC 890 Study

, INVESTIGATOR AND STUDY CENTER

.,. ; . ......

UNITED KlNGDOM

Page 9

... : . . I . .. . ..

~age 10

COMPANY PERSONNEL

l PRINCIPAL CLINICAL PROJECT CO-ORDINATOR

M.D. Medical Department Leo Pharmaceutical Products DK-2750 Ballerup DENMARK

LOCAL CLINICAL PROJECT MONITOR

Department Leo Laboratories Limited longwick Road Princes R.isborough Bucklnghamshire HP17 9RR UNITED KINGDOM

SECRETARIAL FUNCTIONS AND DATA COMPUTERJSATION

ln:> ,.,.,.,nnt

Leo Pharmaceutical Products DK-2750 Ballerup DENMARK

. . : .. .....

MC 890 Study

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MC 890 Study Page 11

, The following description up to and including Section 9, COMPLIANCE WITH ETHICAL

RESPONSIBILITIES, presents a synopsis of the protocol. The protocol itself is presented in

Appendix I.

1 OBJECTIVE OF THE STUDY

To assess the acceptability and tolerability of caldpotriol solution in patients with

scalp psoriasis.

2 DESIGN OF STUDY

An open, single-center pilot study. Treatment with caldpotriol solution 50 ~g/ml

for 6 weeks.

3 CRITERIA FOR SELECTION OF STUDY PATIENTS

3.1 INClUSION CRITERIA

3.1.1 Clinical diagnosis of scalp psoriasis.

3.1.2 At least 18 years of age.

3.1.3 Either sex.

3.1.4 . Women of child-bearing potential using adequate method of contraception.

3.1.5 Written informed consent given.

. . . .. , . . J

I Page 12 MC 890 Study

3.2, EXCLUSION CRJTERIA

3.2.1 Pregnant or breast-feeding femal~s.

3.2.2 Current medication with > 500 iu. vitamin D daily or calcium tablets.

3.2.3 Known or suspected of not being able to comply with a study protocol.

3.2.4 Hypercalcaemia. (Defined as serum caldum (total) above the upper limit of normal

for the local laboratory).

3.2.5 Significant renal disease. (Defined as serum creatinine greater than 1.5 times the

upper limit of normal for the local laboratory).

3.2.6 Significant hepatic disease. Defined as either:

a} serum aspartate aminotransferase or alanine aminotransferase greater

than 1.5 times the . upper limit of normal for the local laboratory.

or

b) serum alkaline phosphatase greater than 1.5 times the upper limit of

normal for the local laboratory.

4 CRITERIA FOR EARLY WITHDRAWAL FROM THE STUDY

4.1 Patient's voluntary withdrawal.

4.2 Medical deterioration.

4.3 Any unacceptable adverse events.

4.4 EXclusion criteria emerging during the study. . ...

... .... .. ;.. ' ~ .


4.5 Persistent Hypercalcaemia: If the patient had a serum calcium (total) above the

upper limit of normal on more than one occasion during the study, the patient was

withdrawn.

5 STUDY MEDICATION

CaJdpotriol solution containing 50 JJ,g/mJ of calcipotriol in the following vehicle:

Isopropanol Hydroxypropylcellulose Menthol Sodium citrate Propylene glycol Purified water

Batch no.: 902231101.

Manufactur:ed and certified by leo P~armaceuticaJ Products, Bal1erup, Denmark

August, 1990. Expiry date: February, 1992.

5.1 STORAGE OF STUDY MEDICATION

Study medication was stored at room temperature {i.e. below 25C).

5.2 ADMINISTRATION OF STUDY MEDICATION

The medication was applied twice daily (morning and evening). A few drops were

applied to affected skin on the scalp and rubbed in lightly. Care was taken not to

allow the solution to run on to the face. Patients were instructed to wash their hands

after application to avoid inadvertent spread of .the solution.

Occlusion or other treatment of the scalp was not permitted.

' ' I -'

- - ' 1 . .... .. . . .


1

5.3- DURATION OF THERAPY

Six weeks.

5.4 SHAMPOO

A non-medicated shampoo, Sunsilk~- Normal hair, was provided for use during

the study. Hair could be washed 2- 3 times weekly. The hair was to be dried before

applying the study medication.

6 CONCOMITANT THERAPY

Concomitant medication for conditions other than psoriasis was continued

throughout the study. No anti psoriatic scalp medication (except that with test drug)

was allowed during the study period. Topical antipsoriatic medication (medium

strength steroids, tars and dithranol) were allowed on the upper extremities, trunk

and lower extremities.

Administration of any concomitant medication was recorded in the Case Record

Form. Use of the non-medicated shampoo was permitted throughout the study.

7 STUDY PROCEDURES

Visit 1 2 3 4

(Weeks) (0) (2) (4)" (6)

MedkaJ History X

Clinical Assessment X X X X

Laboratory Assessments X X X

Adverse Events X X X

I , - . . .. .. . , .... ..: ... _ .. . : .. .. :


' 7.1 MEDICAL HISTORY (visit 1)

At visit 1 the patient's history of psoriasis, demographic data and all aspects relevant

to the protocol's inclusion and exclusion criteria were recorded and evaluated.

7.2 ACCEPT ABILITY ASSESSMENT

7.2.1 Patient's assessment

At each visit the patient was asked specific questions regarding the acceptability

of the medication as follows:

''Did the solution sting or bum?" ''Was it painful in any other way?" "Was it

soothing?''

Full details including inddence, duration, severity, chronological relationship to

medication applications were recorded.

7.3 CLINICAL ASSESSMENT

7.3.1 Investigator's assessments

The investigator made the following clinical assessments:

7.3.1.1 ~?~~~~~n! _o! ~l:e_ ~x!:_n! _o! ~c:_a~~ p:o_ri_a:i~ At each visit the investigator assessed the area of scalp a~fected (cml):

7.3.1.2 _:\_s:~:~~n_! _o! .?!~~a! _s~g_n? At each visit the investigator assessed the severity of redness, thickness and scaliness

on a 5-point scale ranging from 0 = no to 4 = most severe.

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I Page 16 I

7.4

I

17.4.1

7.4.2

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MC 890 Study

LABORATORY EXAMINATIONS

Blood samples for analysis of the variables listed below were taken at visits 1, 2 and

4 (or earlier if patient withdrawn).

Haematology

s1>-haemoglobin B-erythrocytes B-leucocytes (total count) B-leucocyte differential count B-pJatelets

Blood chemistry

s2>-bilirubin (total) S-alkaline phosphatase S-aspartate aminotransferase (ASAT) or S-alanine aminotransferase (ALAT) S-creatinine S-calcium (total) S-phosphate S-albumin

7.5 RECORDING OF ADVERSE EVENTS

I) B = Blood. 2

> s-= s.- -

In addition to the specific questions on acceptability of calcipotriol solution (see

7.2.1), the investigator asked the patient: "Since I last saw you, has the treatment

upset you in any way or have you noticed any uncharacteristic skin changes on the

scalp?". If so, the nature, date of onset, duration, severity ("mild~, "moderate" or

"severe~) and causal relationship to trial medication ("unlikely", "possible" or

"probable") were recorded.

The investigator also observed the patient's scalp for any uncharacteristic skin

changes which were recorded.


Any serious and unexpected adverse events were to be reported to the Company

immediately (ie within 24 hours).

8 PRESENTATION OF RESULTS

i) a subjective assessment of the overall acceptability of the solution was

made by the investigator.

ii) all laboratory parameters were compared from baseline to each successive

visit.

iii) all adverse effects were documented. Those which were classified as

"possibly" or "probably" related to study drug were listed.

iv) all spedfic experiences reported were listed. The severity, type and

persistence were documented.

9 COMPLIANCE WITH ETHICAL RESPONSIBILITIES

9.1 The investigator signed a statement to confirm that:

9.1.1 the study would be conducted to conform with the Declaration of HeJsinki II as

adopted by the 18th World Medical Assembly, 1964, and revised by the 29th World

Medical Assembly, Tokyo, 1975, and Venice, 1983

9.1.2 the patient only participated after giving signed informed consent having received

verbal and written information about the study. The information emphasized that

participation in the study was voluntary and that the patient couJd withdraw from

the study at any time and for any reason

9.1.3 the clinical trial was approved by the Medicines Control Agency in the United

Kingdom and the local Ethics Committee.

9.2 Patients were covered bv the Product liability insurance of leo Pharmaceutical Products.

MC 890 Study

.. .:


' 10

10.1

10.1.1

RESULTS

STUDY PERIOD

Study start

The first patient attended visit 1 on November 7, 1990 and started using the trial

medication on the same date.

10.1.2 Study completion

The last patient who completed the trial stopped medication on January 16, 1991.

10.1.3 Duration of the study

The total duration of the study was approximately 2 months.

Individual data on dates of visits 1 - 4 are listed in Table I.

Table I: Dates of visits attended

Pt. Age Stx Visit 1 Visit 2 no . (yrs) (dd/moa/yy) (dc!/IMI/yy)

I I I I I I I I I I I I 'I I I I I I I I . . lllun (SO)::-.. , ..

Range Numb~r u

I IPage 20 MC 890 Study

I I 10.2 STUDY POPULATION

10.2.1 Disposition of study subjects

10.2.1.2

A total of 11 adult patients were evaluated for participation in the study and seen

at visit 1.

A total of 5 patients were withdrawn from the study, 3 patients defaulted, 1 after

visit 2 and 2 patients after visit 3. One patient withdrew at visit 3 because of

"deterioration of psoriasis" and one patient withdrew at visit 3 because she found

"the treatment painful~ and that the treatment "did not help".

10.2.2 Protocol violators

The protocol listed a number of inclusion and exclusion criteria {see Section 3) with

which the patients had to comply o be eligible for receiving treatment.

All of the patients complied with the protocol eligibility criteria.

MC 890 Study

' 10.2.3 Disposition of study subjects - flow-chart

EJ Visit 1

dJ Visit 2

Default

Visit 3

Def aul.t Withdrawn

Visit 4

One patien t withdrew because of deterioration of psoriasis One pat i ent withdrew because of unacceptabte adverse events

10.3 BASELINE DATA

Data recorded at visit 1 for the 11 patients receiving trial medication.

10.3.1 Sex distribution

One male and 10 female patients were included in this study (Table II).

10.3.2 Age

Patients' mean age was 51.2 years (range 23 - 82) (Table II).

Page 21

.. . . .. ~ . . . . . .


10.3.4

10.3.5

Ten out of 11 patients had psoriasis on other areas of the body, treatment of these

lesions are listed in Table IV.

Table IV: Treatment of psoriasis on tke body except scalp at baseline ... :?

. ,;::.-!::.:: .. '.:" .. : . ... .

Pat ient Age Sex Pso~iaais on oth~ no . (yn) areas o r the body

I I Yes I I Yes I I I Yea I I Yes I I I Yes Eollient ... . ::::.:: I I I No I I Yes I I I Yea I I I Yea I Yea I I Yea

Concomitant drug treatment

Two patients received concomitant drug treatment, listed in Table V. There was no

change in concomitant treatment during the study.

Table V: Concomitant drug treatment at baseline

Patien t Age Sex Drug Dosage no . (y r s J

I I I Cyclopenthiazide o.s 1111 : "Diabetes tablet" I I Warfarin 8 IDS ' Nepro nn soo a .:.

Extent and severity of patients' scalp psoriasis

Extent and severity of scalp psoriasis are indicated in Table VI.

I -. . ~ , ~

I Page 24 Me 890 Study

I I

Table VI: Extent and severity of scalp psoriasis at baseline

Pt . Age Sex txt~n t Redne~s no . { y rs ) ( ~' ) ~core

I I I 60 3 I I I 10 2 I I I 20 3 I I I 20 3 I I I 15 2 I I I 80 3 I I I 48 4 I I I i scalp 3 I I 30 2 I I 30 3 I I 2S 2 ~eiSII ( SO) 39 7 (28.8 \ 3 ( l) Ranae 10 ~ ao 2 .. 4 Numbe r 11

ll Scor~ : 5- po l n t ca l e (0 ~ none 4 ~ most severe )

10.4 DURATION . OF TREATMENT

. Thic:~ess score

3

2

4

2

3 .. 3

3

3

J . .

2 .:

2

. 3

. 9 '

6 . . .: -....... : .. ...

3 (l J l (1): 8 . 7 . (L2)


10.5.1

Does the solution sting?

Does the solution burn?

Was the solution painful in any other way?

Was the solution soothing?

Stinging

Five patients reported stinging at one or more visits during the study, 2 patients

found the stinging "severe" or "moderate". All 5 patients considered stinging to be

"possibly'' or "probably" related to the study drug.

The number of patients who experienced stinging at each visit and the severity,

duration and relationship to study medication for each reported episode are shown

in Tables VIla - d.

Table VIla: Clinical assessment, all visits. Stinging

Pat i ent Age no. (yr s)

Self

SUl!l

Visit 2 ,

Yes Not att.

y.,s No No No Yes No No No No

3

Visit 3.

Yes Yes Y~s NO No Yea

Not att ;: . : No No No No. .,

. :

Table VIIb: Clinical assessment, visit 2. Stinging

Pt. Ag~ Sex no. (yrs )

Expe ri-ence

Yes Yes No No No Yes

No No No No

3

Severity

Severe Mild

Severe

Relal ionahip to s tucly

dM.Ig.

Probable. Probabll'

Probable Hours

.. ...

Page 26

10.5.2

Table VIle: Clinical assessment, visit 3. Stinging

Pt . Age Sex Experi-no. ( yra ) e nc:e

Yta Yes Yes No No Yes NQ No NQ No

::::::C',:=;: : II

Seve rity

!Oioderate Mi ld Mild

Mild

Relationshi p t o study

d rug

Possible Probable Probable

Probable

Tiree l u ting

Hours Seeoncia ~inutea

Second&

Table VIId: Clirrical assessment, uisit 4. Stinging

Pt. Age Sex Esperi-no. (yrs) enc e

Ill ~r :.

1

Burning

Severity

Mi l d

Relationship to study

dru r

Probable

Tillie las t inc

Second a

No . or days s ince laat viait

10 All All

All

MC 890 Study

. . ftdaUon-. Re la t ed. to . ship to. previous '

applica - experi~nee. tion.

None None None

None . :

~ .: , :~ . . ; . . .

~ .. ' . wa.: : .. .~ . . . : . . :. ~.::' :

Ho . ot Relation,: , Related;: to , :t day:a sinc e a hip . ta:,.._::.:.:. preVious. .. :e:~-: last visit. applica- v-.~ exp.;rhnee

MC 890 Study

Table VIlla: Cliniclll assessment, all visits. Burning

l'ati~nt no,

SUN

Age (yr)

Sex Vlsl t 2

Yes

No No No No Yes No 'tea No No

3

Visit 3

Yes No llo No No No

Not ott, No -No No No: .

1. '

Table Vlllb: Clinical assessment, visit 2. Burning

Pt. no.

Age Sex (yrs)

Ex peri-rnce

Yes No No No No v ... No Yes No No

1111:A::~~ ~~a

Severity

Severe

Mild

Relationship to stud)l

.....

Page 28 MC 890 Study

10.5.3 Pain

10.5.4

10.5.5

One patient withdrew at visit 3 because she found the treatment painful. No other

patients considered that the solution was painful.

Soothing

Four patients considered that the solution was soothing at one or more visits. The

number of patients who considered the solution soothing at each visit are shown

in Table IX.

Table IX: Clinical assessment, all visits. Soothing

Patient Ase no. _(yrs)

Sex Vi& it 2 Visit 3

No No Not att. No

No No No No /lo No Yes No No Nat att. Yes Yes. No Yes No No No No

SUM 2 2

Other observations

The number of patients who mentioned any other observations at respective visits

and the severity, duration and relationship to study medication for each reported

episode are shown in Tables Xa - b.


10.6

10.6.1

Table Xa: Clinical assessment, all visits. Other observations

Pati.ent Age no. (age)

SUM

Sex At visit 2 specitication ot ether obs.

Scali) dry

TreatDcnt did not help

Vldt.2

No

No Yes. No .. . . No

NO'" :

No. No

Table Xb: Clinical assessment, visit 2. Other observations

Pt. Age no. (yrs)

Sex xperi- Type cnce or

No No Yea

No No

expe-rience

Scalp dry

Seve-rity

Mild

Relation- ship to study druc

Probable Seconds;

Treatment did not help No

No No

ll::::

. .

EFFECT OF CALCIPOTRIOL SOLUTION ON SCALP PSORIASIS

Effect on total sign score

The mean reduction in total sign score (ie sum of scores for redness, thickness and

scaliness) from start to end of treatment was 2.7 (range 0 - 7).

Table XI shows the total sign scores at respective visits and the changes in total sign

score from baseline to end of treatment for all patients.

:>age 30

10.6.2

.. ...... .... ~ . . 7'.

MC 890 Study

Table XI: Clinical assessment, ail visits. Total sign score.

Pt . Age Sex no. (yrs)

IIIEAN (SO) RANCE NUMBER'

~ ~ 8 9

10 10

9 10 8

8.7 (1.2)' 6 .. 10

11

Visit.,~ I CO t"e

VIsit.~~ a


The mean reduction in score for thickness from start to end of treatment was 1.0

(range 0 - 2). The scores for thickness at respective visits and . the changes from

baseline (visit 1) to end of treatment for all patients are shown in Table XIII.

Table Xlll: Clinical assessment. Scores for thickness

Pt . Age Sex Viait111 no . (yrs) score

) ) . ) 2 Not att. 1 4 ) 3 2 2 1 ) 2 2 3 2 2 3 3 Not att'. 3 2 2

~ ) 2 2 2 3 2 1

1. 8 ' (1. 0 ) ' 1. - .3: .

6

MEAN (SD) J .O (0 . 6) 2 . 4 (0. 5) 1.9 (0 .7) RANCE: 2 - 4 2 - 3 1 - 3 N~BER 11 10 10

ft Score: 5-polnt scale (0 = none - 4 =oat Ievere)

The mean reduction in score for scaliness from start to end of treatment was 1.0

(range 0 - 3). The scores for scaliness at respective visits and the changes from

baseline (visit 1) to end of treatment for all patients are shown in Table XIV.

Table XIV: ClinicaL assessment. Scores for scaliness

Pt. Age Sex Visit 111 Vlsit 112 Vhlt11J , vis it n~:i.\_ no. ( yn) score score ccore , acor~ .. ..

Not . .

2 2 3 a it : ... 3 Not lltt. 1 . :;f'!:;~: ... 2 2 2 3 2 2 -r :_.;:> 3 2 2 3 3 3 .. - 2 .. : ..

~ 3 Not att . Not att. 2 2. 1 II ~ 3 Not att. 3 2 Not a t t'. 3 2 2 Not at t.

MEAN (SO) ).0 (0.6) 2.5 (0 .7) 2.2 (0. 6) . RANCE 2 ~ 4 2 ~ 4 1 ~ - ) ' NUMBER 11 10 10

.,: 11 Sco!'e: 5-point scale (0 " none ~ 4 =most severe)

MC 890 Study

10;,6.3 Extent of scalp psoriasis

Table XV shows the extent of scalp psoriasis at respective visits and the changes in

extent from baseline to end of treatment for all patients. Four patients had a

reduction in extent recorded (range 10 -.. 60 cnf~) and 6 patients experienced no

change in extent of their scalp psoriasis.

Table XV: Clinical assessment, all visits. Extent of SCillp psoriasis

Pt. Age Sex Vis.it 1 Visit 2 Viait 3 no. (yrs) cm1 era'


If the patient's answer to the open question was "NO'', no further questions were

asked.

Further, the investigator observed the patient for adverse effects on the scalp.

For each adverse event, the following related details were recorded in the Case

Record Form.

1) The adverse event in the investigator's own terminology.

2) Date of first occurrence.

3) The number of days since the preceding visit that the patient was affected by

the adverse event.

4) The investigator's opinion on the severity of the adverse event, classified as

''mild", .''moderate'' or ''severe".

5) Whether the investigator consid~red the. relationship of the adverse event to the

study drug to be ''unlikely", "possible" or "probable".

In the analysis and presentation of adverse events, the following approach was used:

A particular adverse event was counted only once for each patient, even if the

adverse event was recorded repeatedly.

The individual adverse event data, using the investigator's terminology, are

presented in Table XVI.

I I Page 34

10.8.2

MC 890 Study

Table XVI: Adverse events reported/observed after start of treatment

Date or .,Dura- . Reta'tton,.:, s~v~rity:::

u~~~) , .:~~~.:~~i: .. _.:':: .::-: Pt. Age Sex Visit no. (yrs) no.

Adverse event

Ill 3 3 2 So~e extension ot psoriaais -Some irritation - 14 . p'~ob~bl)' :..:~~~~:~ ~~.':? 7 . . . Pro~brc: .. ,~. severe = '.:, . .. :: : .:.~ : .~ ::.~ .. ~::f~ily:. .;': -~- ~-;~i~

' ~


Table XVIIb: Laboratory assessment: Blood erythrocytes, all visits. Reference interval for patient no. 1-9: M: 4.5-6.5; F: 3.8-5.8 .x 1012/J; for patient no. 10-11: M: 4.5-6.5; F: 4.0-5.8 X 1012/l

Patient Age Se:~t Visit 1 Vi.5it 2 Visit 3 no. (yrs)

"~~~ 4.45 4. ~ No~ att. 4.2 ~.19L ~.22L

.19 .16

~:6~L 4.68 ~.82L ~:~~L .60

Mean (SD) 11 . 14 (0 .48) ~.12 (o.saA Ranae 3.19- li.o 3.22 .. ll.6 N1.111ber 9 6

I II I 4.44L 4.67 4.71 H: Value above upper li111i t ot the reference range. L: Value bela~ lower limit ot the reference range

Vlsi t 11 :': . C:l;anae'a CrOll ~ ot~rt =''~.:: .... .to end of. treatlle~~~':{

Table XVIIc: Laboratory assessment: Blood leuc~tes, all visits. Reference interval for patient no. 1 - 9: 4 - 11 10 2!1; for patient no. 10 and 11: 4 - 11 10~211

Patient Age Su: Vis lt 1 Visi t 2 vi"s it , j no. (yrs I . ..

U.aH 6. 9.3 Not at't. 12:4H b. 7.2 6.2 s.

12 . 4H 10 . 7.6 7.7 6.9 ~ L Not att. .7 4 . 1 6.0 6.7

Mean (SO) 1~ (2 .9) ,.5 (2 . J) 8l ().6) Range J. .. 12.4 .1 6 10.6 6. : .. 12.9 Nu11ber 9 3

I I I 7 .l s.ll 8.6 H: Value above upper limit of the C"eterence: range L: Va lue below lower limit ot the . r"eference ranae

MC 890 Study

Table XVIId: Laboratory assessment: Blood platelets, all visits. Reference interval for patient no. 1-9: 150-400 109/1; for patient no. 10-11: 140-380 zo9;z

Pati

278

~~6 256 2')4 236 321 2l2 2 6

Mean (SD) 276 (321 Ran1c 236 ~ 335 Nu11ber 9

I II I 360 1 8 H: Value above U?per lioai t or the L: Value below lower lioail of the

Visit 2

274 Not att .

270 220 22')

253 250

249 122) 220 ~ 274

6

332

rererenc:e rc!crcnc:e

Visit 3

311 337

200 l'iot att .

283 (73) 200 ~ 337'

3

range range

Visit _ ..

Not att. 352 2116 272 212 .

Not att . 260.- .

Not att .:

.... . Not ate. Not att.,:

cr.An8ea trm.:Stat.t. .. :: .. .to end or:- treatment . .

. ... . ':

.. : .. :. :: ...... ~ ..... :::

Table XVIIe: Laboratory assessment: Serum bilirubin, all visits. Reference interval. for patient no. 1 - 9: 3 - 15 gmoVl; for patient no. 10 and 11: 3 - 15 gmoVl

Patient Age SclC Viai t l no. (yra)

6 12 6 6

6 7

l Mean (SD) z (2) Range - 12 llu111ber 8

I I 6 6

Visit 2

6 Not ott.

6 3 7

l 6 (2) 3 ~ 9

7

8 6

Visic 3

5 No t att.

7

7 (3) 5 ~ ~.:

4

7 9

. H: Value above upper lim i t ot the reterence ranse L: Val ue below lower l imit of the reference ranse

Not att .' 8 g 4

Not att'.

Not att-. .. .

.,="~ ~ J_': -~:~~J.:;;.ff(,1~~;I\ . 2 '

MC 890 Study 'Page 37

Table XVII: Laboratory assessment: Serum alkilline phosphatase, all visits. Reference interval for patient no. 1 - 9: 4-13 lUll; for patient no. 10 and 11: 56-241 lUll

Patient Age Sex V.iai t 1 Visit 2 Visit 3 no . (ye-s)

visit 11. ~:~- chana~~f~r~:-~t'~~-t\),:, . to end . .' of:-: t reatlllent .. ,::-

3.7L ).6L 4.2 10.0 Not a~t ; 9. 0 ~-6 ~-6 .J .4

11.8 93

4.:! s.o 6.11L Not: att . .o s.4 6.5 4.3

Mun (SD) s.,c2.t} 5.6 c2.o) Range J. - 10.0 J.6 - 93 NUJ~~bcr 8 6

I II I 251H 236 261H 112 116 114 H: Value above u pper limit of the reference ranee L: Value below l awer 1 i lli t of the referen ce ranee

Table XVIIg: Laboratory assessment: Serum aspartate aminotransferase, all visits. Reference interval: 11 - 35 lUll

Patient Ase sex Vidt 1 Visit 2 Visit 3 no. (yrs)

~~ 29 24 Not at t. 16 32 31 24 16

)8H 14 .

i~ 15 Not att . 16 16 13 17 20

:~!can (SD) 22 (8) 24 (9) 17 (5) Range 15 - 311 15 ~ 38 13 ~ 24: Nu.,ber 8 7 4 :

H: Value above upper l i mit o f t he reCerence ranse L: Value be low l ower limit ot the rete renee ranse

' :~ :

Table XVIIh: Laboratory assessment: Serum alanine aminotransferase, all visits. Reference interval: 0 - 35 lUll

Patien t Ase Sex no. (yt's)

I I I

Visit 1

34 17

Visi t 2 Visit 3

u : . 17' ' .


Table XVIIi: Laboratory assessment: Serum albumin, all visits. Reference interoal for patient no. 1 - 9: 37 - 49 mmol/1; for patient no. 10 and 21: 37 - 49 mmol/l

Patient Age Sex Vlsit 1 Visit 2 no. (yl'S)

42 41 43 Not a t t . 47 b7 42 112

42 41

4:) liS

~ 110 44

Mean (SO) 113 (2, 113 (2! llanae. bl - 7 llo - 7 Nu111ber 8 7 ..

I I I ~~L ~~ H: Value above upper l i~it of the reference range L: Value below lower limit o f the reference range

40 46

Vide 11: ' .: . : ' ch~~~~,:,cr~:'at'art.'?~-. , .:- . to encl o,f.: treatn.ant;:--:.:

. ::~.:.i.: . . ;.;

.. :,

Table XVIIj: Laboratory assessment: Serum caldum (/olal), all visits .. Reference interval for patient no. I - 9: 2.25 - 2.60 gil; for patient no. 10 and 11: 2.2 - 2.6 gil

Pathnt Age Sex Vl.sit 1 Visit 2 Visit J- : no ; (yrs)

:

2 . 44 2. J8 2.111 . 2 . )1 Notatt. 2.)0 2 . ;~ 2. 49 2. 3 2. 35

2 . )6 2.13

2.)6 2. s 2.30 Not att. 2.34 2.26 2.37 2.JJ

Mean (SO) 2.J7 (0.08) 2-3z (0 .08) 2.)6 (0.0~) " Range 2. )0 - 2.53 2.2 . .. 2.49 2.3o- 2. t Number 8 6 . 4

I I I 2.26 2.JJ 2.19 2.)4:. 2.15 H: Value above u~per limit o t the r~terenc:e range L: Value be low lower l i mi t or the r


Table XVIIk: Laboratory assessment: Serum phosphate, all visits. Reference interval for patient no. 1 ...: 9: 0.8 -1.3 mmol/1; for patient no. 10 and 11: 0.8 -1 .3 mmol/l

Patient Age no. (yrs)

Mean (SO) Ranse Nwaber

I I

Su

I

Vis i t 1

0.94 O.

.. .. . .. . - . ... .... . - ... . . . . ... , .. ..... ~.

Page 40 MC 890 Study


11 CONCLUSION

The study showed that the acceptability, safety and efficacy of twice daily application

of calcipotriol solution (SO ~g/ml) should be further investigated in large, well-

controlled studies of patients with scalp psoriasis.

clinical study report - leo-pharma.comleo-pharma.com/files/filer/leo_corporate_downloads/clinical...

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