Efficacy and Safety of Two Doses of Liarozole vs. Placebo for the Treatment of Lamellar Ichthyosis

Ichthyosis, Lamellar Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00282724
• Other study ID #: BT0500INT001
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 20, 2006
• Last updated: September 23, 2011
• Start date: January 2006
• Est. completion date: April 2007

Study information

• Verified date: September 2011
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Netherlands: Medicines Evaluation Board (MEB)Italy: The Italian Medicines AgencySweden: Medical Products AgencyNorway: Norwegian Medicines AgencyCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: April 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Ichthyosis
• Ichthyosis, Lamellar

Intervention

Drug:
• Liarozole

Locations

Country	Name	City	State
Belgium	Academisch Ziekenhuis Vrije Universiteit Brussel	Brussels
Belgium	Geel	Geel
Canada	Hôpital Saint-Justine	Montreal
Canada	Newlab Clinical Research Inc.	St John
Dominican Republic	Instituto Dermatologico	Santo Domingo
France	Hôtel Dieu CHU	Nantes
Germany	Tomesa Fachklinik	Bad Salzschlirf
Germany	Dueren	Dueren
Germany	Otto-von-Guericke-Universität	Magdeburg
Germany	University Hospital Muenster	Muenster
Italy	Fondazione Policlinico Mangiagalli e Regina Elena	Milano
Italy	Istituto Dermopatico dell'Immacolata	Rome
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	University Hospital Rotterdam	Rotterdam
Norway	Rikshospitalet Universitetsklinikk	Oslo
Sweden	Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Stiefel, a GSK Company

Countries where clinical trial is conducted

Belgium,  Canada,  Dominican Republic,  France,  Germany,  Italy,  Netherlands,  Norway,  Sweden, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy: Investigator's Global Assessment
Secondary	Overall Scaling Score
Secondary	Severity scores of other symptoms
Secondary	Quality of Life
Secondary	Safety and tolerability
Secondary	Pharmacokinetics