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

Sponsor:	Stiefel, a GSK Company
Information provided by (Responsible Party):	GlaxoSmithKline ( Stiefel, a GSK Company )
ClinicalTrials.gov Identifier:	NCT00282724

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: lamellar ichthyosis nonbullous congenital ichthyosiform erythroderma

Drug Information available for: Liarozole Liarozole fumarate

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

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

Enrollment:	98
Study Start Date:	January 2006
Study Completion Date:	April 2007
Primary Completion Date:	April 2007 (Final data collection date for primary outcome measure)

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
Tomesa Fachklinik
Bad Salzschlirf, Germany
Dueren
Dueren, Germany
Otto-von-Guericke-Universität
Magdeburg, Germany
University Hospital Muenster
Muenster, Germany
Italy
Fondazione Policlinico Mangiagalli e Regina Elena
Milano, Italy
Istituto Dermopatico dell'Immacolata
Rome, Italy
Netherlands
Academisch Ziekenhuis Maastricht
Maastricht, Netherlands
University Hospital Rotterdam
Rotterdam, Netherlands
Norway
Rikshospitalet Universitetsklinikk
Oslo, Norway
Sweden
Uppsala University Hospital
Uppsala, Sweden

Sponsors and Collaborators

Stiefel, a GSK Company

Investigators

Study Director:

Koen van Rossem, MD, PhD

Barrier Therapeutics/ Stiefel, a GSK Company

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.

Responsible Party:	GlaxoSmithKline ( Stiefel, a GSK Company )
ClinicalTrials.gov Identifier:	NCT00282724 History of Changes
Other Study ID Numbers:	BT0500INT001
Study First Received:	January 20, 2006
Last Updated:	September 23, 2011
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 GlaxoSmithKline:

Lamellar ichthyosis
Liarozole
Investigator's Global Assessment
Scaling

Additional relevant MeSH terms:

Ichthyosis
Ichthyosis, Lamellar
Skin Abnormalities
Congenital Abnormalities
Infant, Newborn, Diseases
Keratosis
Skin Diseases
Ichthyosiform Erythroderma, Congenital
Skin Diseases, Genetic
Genetic Diseases, Inborn
Liarozole

Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Dermatologic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on February 12, 2012