Clinical Trials Register

Summary
EudraCT Number:	2010-023482-21
Sponsor's Protocol Code Number:	01/10/CPT/TP3
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-02-28
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2010-023482-21

A.3

Full title of the trial

A Multicentre, Randomised, Double-Blind, Parallel-Group Study of the Efficacy and Safety of a PLIVA Ointment (Calcipotriol + Betamethasone 50 µg/g + 0.5 mg/g ointment) versus Vehicle and Dovobet® in the Treatment of Mild to Severe Plaque-Type Psoriasis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical Study comparing Efficacy and Safety of PLIVA Ointment with Dovobet® and Placebo Ointment in the Treatment of Mild to Severe Plaque-Type Psoriasis

A.4.1

Sponsor's protocol code number

01/10/CPT/TP3

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PLIVA HRVATSKA d.o.o.
B.1.3.4	Country	Croatia
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	PLIVA HRVATSKA d.o.o.
B.4.2	Country	Croatia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PLIVA HRVATSKA d.o.o.
B.5.2	Functional name of contact point	PLIVA HRVATSKA d.o.o.
B.5.3	Address:
B.5.3.1	Street Address	Prilaz baruna Filipovića 25
B.5.3.2	Town/ city	Zagreb
B.5.3.3	Post code	10 000
B.5.3.4	Country	Croatia
B.5.4	Telephone number	+ 3851 37 20 000
B.5.5	Fax number	+ 3851 37 20 111
B.5.6	E-mail	info@pliva.hr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	PLIVA Calcipotriol + Betamethasone 50 µg/g + 0.5 mg/g
D.3.2	Product code	PLIVA Calcipotriol+Betamethasone 50 µg/g+0.5 mg/g
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent) Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	calcipotriol
D.3.9.1	CAS number	112828009
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Betamethasone Dipropionate
D.3.9.2	Current sponsor code	5593-20-4
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Dovobet® ointment
D.2.1.1.2	Name of the Marketing Authorisation holder	LEO Pharmaceutical Products, Ballerup, Denmark
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent) Cutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CALCIPOTRIOL
D.3.9.1	CAS number	112828009
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.05
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BETAMETHASONE DIPROPIONATE
D.3.9.1	CAS number	5593-20-4
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Ointment
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

mild to severe plaque psoriasis

E.1.1.1

Medical condition in easily understood language

mild to severe plaque psoriasis

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	LLT
E.1.2	Classification code	10050576
E.1.2	Term	Psoriasis vulgaris
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

• To compare the relative efficacy, safety and tolerability of the PLIVA ointment of calcipotriol + betamethasone to the already marketed Dovobet® ointment (calcipotriol 50 microgram/g, betamethasone 0.5 mg/g, Leo Laboratories Limited, UK) in patients diagnosed with mild to severe plaque psoriasis
• To compare test product to a vehicle ointment (placebo) testing for superiority

E.2.2

Secondary objectives of the trial

No secondary objective.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males or females >= 18 years of age;
2. Clinical diagnosis of plaque psoriasis;
3. Mild to severe psoriasis, as defined by an Investigator’s Static Global Assessment (ISGA) score of at least 2 at Baseline greater than or equal to 10% of one body segment (arms, or legs, or trunk) and less than or equal to 30% of total body surface area (BSA) affected (excluding the face and scalp);
4. Target lesion (greater than 2 cm2) on the trunk or extremities (excluding palms/soles) with a score of at least 2 (on a 0-5 scale) for each of erythema, scaling and plaque thickness;
Whenever possible, psoriasis on knees or elbows should not be used as a target lesion.
5. Good general health, as confirmed by medical history and physical exam, and free from any clinically significant disease/condition, other than plaque psoriasis, that might interfere with the study evaluations;
6. Females of a child-bearing potential must have a negative urine pregnancy test at the study entry. They must agree to use a medically-acceptable method of contraception during the study (IUD or double barrier (condom with a contraceptive sponge or contraceptive suppository) or oral contraceptive or subdermal implant).
Not applicable for post-menopausal women (at least 1 year prior to inclusion) and women after surgical sterilization;
7. The ability and willingness to follow all study procedures, attend all scheduled visits, and successfully complete the study;
8. The ability to understand and sign a written informed consent form, which must be obtained prior to participation in this study;
9. Willingness to keep sun exposure reasonably constant and to avoid use of tanning booths or other UV light sources during the participation in the study.

E.4

Principal exclusion criteria

1. Any form of psoriasis other than plaque-type (e.g. guttate, erythrodermic, exfoliative, pustular);
2. Known disorders of calcium metabolism;
3. Abnormal serum calcium levels at baseline (> 10% above the ULN);
4. Known kidney stones;
5. Viral, fungal, parasitic or bacterial skin infections, skin manifestations in relation to tuberculosis or syphilis, rosacea, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers, wounds;
6. Other serious skin disorder, disorders that may interfere with the evaluation of plaque psoriasis (e.g., atopic dermatitis, contact dermatitis, tinea corporis) or any chronic medical condition that is not well controlled;
7. Clinically significant systemic disease (e.g., immunological deficiencies), unstable medical disorders, life-threatening disease, or current malignancies;
8. Immunosuppression;
9. Treatment with any systemic steroids within the 4 weeks prior to study entry. (Intranasal or inhaled corticosteroids are acceptable if kept constant throughout the study.);
10. Treatment with systemic or photo antipsoriatic therapies/drugs, other than systemic steroids (e.g., methotrexate, cyclosporine, acitretin, ultraviolet A/ultraviolet B, psoralen ultra-violet A, oral retinoids, mycophenolate mofetil, thioguanine, hydroxyurea, sirolimus, azathioprine, 6-mercaptopurine, tanning booths, nonprescription UV light sources) within 8 weeks prior to study entry;
11. Treatment with any marketed or investigational biologic treatment for psoriasis (e.g., alefacept, efalizumab, infliximab, adalimumab, etanercept, etc.) within the past three months or five half lives of the biologic prior to study entry, whichever is longer. Vaccinations will not be considered an exclusionary biologic treatment;
12. Use of topical treatments that have a known beneficial effect on psoriasis, including but not limited to corticosteroids, retinoids, vitamin D derivatives, tar or anthralin, within the past two weeks prior to study entry or concurrently during the study. Subjects may use blend emollients and other topical therapies (with the exception of vitamin D analogues) recommended by the investigator for psoriatic lesions on areas not treatable with study medication (i.e., face and scalp);
13. Introduction or change in dosage of systemic medications for other medical conditions that are known to affect psoriasis (e.g., lithium, beta adrenergic blockers) within the past four weeks prior to study entry or concurrently during the study;
14. Received radiation therapy and/or anti-neoplastic agents, or taken any immunosuppressive medication within 3 months prior to study entry;
15. Damaged skin or unstable forms of psoriasis in the area to be treated;
16. Excessive exposure to either natural or artificial sunlight;
17. Diabetes mellitus or impaired glucose tolerance (IGT);
18. Severe renal insufficiency;
19. Severe hepatic disorders;
20. History of Cushing’s syndrome;
21. Known hypersensitivity or adverse reaction to the active substances (calcipotriol and/or betamethasone) or to any of the excipients, or related drugs (e.g. other vitamin D analogues, corticosteroids);
22. Drug or alcohol abuse (drug screening not required);
23. Significant history or any co-existing medical condition that in the investigator’s judgement will substantially increase the risk associated with the subject’s participation in the study or could jeopardize the integrity of the study;
24. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures;
25. Females who are pregnant or breast-feeding;
26. Use of any investigational therapy or device within the past four weeks or for five half-lives of the medication prior to study entry (whichever is longer) or concurrently during the study;
27. Previous participation in this study.

E.5 End points

E.5.1

Primary end point(s)

The percentage reduction in Modified PASI score from Baseline to Week 5 (end of treatment).

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Week 5 (end of treatment).

E.5.2

Secondary end point(s)

The proportion of subjects with a target lesion score of 0 for plaque thickness at Week 5 (or
end of treatment);
The proportion of subjects with a target lesion score of 0 or 1 for erythema at Week 5 (or end
of treatment);
The proportion of subjects with a target lesion score of 0 for scaling at Week 5 (or end of
treatment);
The proportion of subjects with a minimum improvement in the ISGA score of 2 grades from
Baseline to Week 5 (or end of treatment);
The proportion of subjects with relapse or rebound within 4 weeks after end of treatment;
Relapse – Modified PASI increased by ≥ 50% at Week 9 after decrease by ≥ 50% from
Baseline to Week 5;
Rebound - Modified PASI increased by >25% or change in the character of psoriasis (e.g.
from plaque to pustular) as defined by Investigator at Week 9.

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of the last subject undergoing the trial.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

651

F.4.2.2

In the whole clinical trial

651

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After the subjects have ended their participation in the trial, they will be treated with other available treatments of plaque-type psoriasis.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-06-03

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-03-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-02-01

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