Efficacy and Safety of Two Doses of Liarozole vs. Placebo for the Treatment of Lamellar Ichthyosis - Full Text View

Purpose

Lamellar ichthyosis is a congenital disease of the skin with a generalized scaling. The primary activity of liarozole is considered to be the inhibition of the degradation of a substance called retinoic acid, which is the principal endogenous regulator of growth and differentiation of epithelial tissues in mammals. The current study intends to evaluate the efficacy and safety in patients with lamellar ichthyosis.

Condition	Intervention	Phase
Ichthyosis, Lamellar	Drug: Liarozole	Phase II Phase III

ChemIDplus related topics:

Liarozole Liarozole fumarate Liarozole hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title:	A Randomized, Double-Blind, Placebo-Controlled Phase II/III Trial to Evaluate the Efficacy and Safety of 2 Doses of Oral Liarozole (75 mg od and 150 mg od) Given During 12 Weeks in Lamellar Ichthyosis

Further study details as provided by Barrier Therapeutics:

Primary Outcome Measures:

Efficacy: Investigator's Global Assessment

Secondary Outcome Measures:

Overall Scaling Score
Severity scores of other symptoms
Quality of Life
Safety and tolerability
Pharmacokinetics

Estimated Enrollment:	98
Study Start Date:	January 2006
Study Completion Date:	April 2007

Detailed Description:

Lamellar ichthyosis is an autosomal recessive disorder that is apparent at birth and is present throughout life. Although the disorder is not life threatening, it is quite disfiguring and causes considerable psychological stress to affected patients. Prevalence is less than 1 case per 300,000 individuals. Treatment is mainly symptomatic i.e. emollients with or without keratolytic agents. Treatment with systemic retinoids is reserved for those patients, refractory to conventional therapy, because of the long-term adverse effects and teratogenicity of systemic retinoids.

Liarozole may provide a new concept for the treatment of this condition. Because of its mechanism of action, retinoic acid (RA) levels will only be increased in tissues that are targets for RA production.

The proposed Phase II/III study intends to evaluate the efficacy of liarozole compared with placebo, in patients with lamellar ichthyosis.

Eligibility

Ages Eligible for Study:	14 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects of either sex aged 14 years or older.
Clinical diagnosis of lamellar ichthyosis
Women of childbearing potential should use appropriate contraception
Women of childbearing potential should have a negative pregnancy test at screening visit.
Subjects are, except for their lamellar ichthyosis, in good general health.
Subjects and legal representative(s), if applicable, signed informed consent.

Exclusion Criteria:

Subject is receiving topical (except emollient), UV treatment or systemic treatment for ichthyosis.
Subject is pregnant or breast feeding.
History or suspicion of alcohol or drug abuse.
Significant co-existing diseases.
Clinically significant abnormal ECG
History of hypersensitivity to retinoids or any of the ingredients in the trial medication.
Clinically relevant laboratory abnormalities at screening.
Use of immune-suppressive drugs including topical or systemic corticosteroids.
Participation in an investigational trial 30 days prior to the start of the trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00282724

Locations


Belgium
	Academisch Ziekenhuis Vrije Universiteit Brussel
	Brussels, Belgium
	Geel
	Geel, Belgium

Canada
	Hôpital Saint-Justine
	Montreal, Canada
	Newlab Clinical Research Inc.
	St John, Canada

Dominican Republic
	Instituto Dermatologico
	Santo Domingo, Dominican Republic

France
	Hôtel Dieu CHU
	Nantes, France

Germany
	Dueren
	Dueren, Germany
	Otto-von-Guericke-Universität
	Magdeburg, Germany
	Tomesa Fachklinik
	Bad Salzschlirf, Germany
	University Hospital Muenster
	Muenster, Germany

Italy
	Istituto Dermopatico dell'Immacolata
	Rome, Italy
	Fondazione Policlinico Mangiagalli e Regina Elena
	Milano, Italy

Netherlands
	University Hospital Rotterdam
	Rotterdam, Netherlands
	Academisch Ziekenhuis Maastricht
	Maastricht, Netherlands

Norway
	Rikshospitalet Universitetsklinikk
	Oslo, Norway

Sweden
	Uppsala University Hospital
	Uppsala, Sweden

Sponsors and Collaborators

Barrier Therapeutics

Investigators


Study Director:	Koen van Rossem, MD, PhD	Barrier Therapeutics

More Information

Publications:

Van Wauwe JP, Coene MC, Goossens J, Cools W, Monbaliu J. Effects of cytochrome P-450 inhibitors on the in vivo metabolism of all-trans-retinoic acid in rats. J Pharmacol Exp Ther. 1990 Jan;252(1):365-9.

Van Wauwe J, Van Nyen G, Coene MC, Stoppie P, Cools W, Goossens J, Borghgraef P, Janssen PA. Liarozole, an inhibitor of retinoic acid metabolism, exerts retinoid-mimetic effects in vivo. J Pharmacol Exp Ther. 1992 May;261(2):773-9.

Van Wauwe J, Coene MC, Cools W, Goossens J, Lauwers W, Le Jeune L, Van Hove C, Van Nyen G. Liarozole fumarate inhibits the metabolism of 4-keto-all-trans-retinoic acid. Biochem Pharmacol. 1994 Feb 11;47(4):737-41.

Kang S, Duell EA, Kim KJ, Voorhees JJ. Liarozole inhibits human epidermal retinoic acid 4-hydroxylase activity and differentially augments human skin responses to retinoic acid and retinol in vivo. J Invest Dermatol. 1996 Aug;107(2):183-7.

Dockx P, Decree J, Degreef H. Inhibition of the metabolism of endogenous retinoic acid as treatment for severe psoriasis: an open study with oral liarozole. Br J Dermatol. 1995 Sep;133(3):426-32.

Berth-Jones J, Todd G, Hutchinson PE, Thestrup-Pedersen K, Vanhoutte FP. Treatment of psoriasis with oral liarozole: a dose-ranging study. Br J Dermatol. 2000 Dec;143(6):1170-6.

Bhushan M, Burden AD, McElhone K, James R, Vanhoutte FP, Griffiths CE. Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2001 Oct;145(4):546-53.

Lucker GP, Heremans AM, Boegheim PJ, van de Kerkhof PC, Steijlen PM. Oral treatment of ichthyosis by the cytochrome P-450 inhibitor liarozole. Br J Dermatol. 1997 Jan;136(1):71-5.

Study ID Numbers:	BT0500INT001
First Received:	January 20, 2006
Last Updated:	September 5, 2007
ClinicalTrials.gov Identifier:	NCT00282724
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices; France: Afssaps - French Health Products Safety Agency; Netherlands: Medicines Evaluation Board (MEB); Italy: The Italian Medicines Agency; Sweden: Medical Products Agency; Norway: Norwegian Medicines Agency; Canada: Health Canada

Keywords provided by Barrier Therapeutics:

Lamellar ichthyosis

Liarozole

Investigator's Global Assessment

Scaling

Study placed in the following topic categories:

Keratosis

Liarozole

Skin Diseases

Keratosis follicularis spinulosa decalvans

Skin Abnormalities

Lamellar ichthyosis

Ichthyosis

Genetic Diseases, Inborn

Infant, Newborn, Diseases

Ichthyosis, Lamellar

Congenital Abnormalities

Skin Diseases, Genetic

Ichthyosiform erythroderma, nonbullous congenital

Tylosis

Additional relevant MeSH terms:

Androgen Antagonists

Antineoplastic Agents, Hormonal

Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents

Therapeutic Uses

Hormone Antagonists

Physiological Effects of Drugs

Hormones, Hormone Substitutes, and Hormone Antagonists

Enzyme Inhibitors

Dermatologic Agents

Pharmacologic Actions

Ichthyosiform Erythroderma, Congenital

ClinicalTrials.gov processed this record on September 05, 2008

Sponsored by:	Barrier Therapeutics
Information provided by:	Barrier Therapeutics
ClinicalTrials.gov Identifier:	NCT00282724