Clinical trial NCT00282724: Efficacy and Safety of Two Doses of Liarozole vs. Placebo for the Treatment of Lamellar Ichthyosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Ichthyosis, Lamellar
Keywords: Lamellar ichthyosis
Liarozole
Investigator's Global Assessment
Scaling
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-01-27
Enrollment: 98
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 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.

Primary outcomes:
measure: Efficacy: Investigator's Global Assessment
Secondary outcomes:
measure: Overall Scaling Score
measure: Severity scores of other symptoms
measure: Quality of Life
measure: Safety and tolerability
measure: Pharmacokinetics
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Academisch Ziekenhuis Vrije Universiteit Brussel
city: Geel
country: Belgium
facility: Geel
city: Montreal
country: Canada
facility: Hôpital Saint-Justine
city: St John
country: Canada
facility: Newlab Clinical Research Inc.
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dermatologico
city: Nantes
country: France
facility: Hôtel Dieu CHU
city: Bad Salzschlirf
country: Germany
facility: Tomesa Fachklinik
city: Dueren
country: Germany
facility: Dueren
city: Magdeburg
country: Germany
facility: Otto-von-Guericke-Universität
city: Muenster
country: Germany
facility: University Hospital Muenster
city: Milano
country: Italy
facility: Fondazione Policlinico Mangiagalli e Regina Elena
city: Rome
country: Italy
facility: Istituto Dermopatico dell'Immacolata
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Rotterdam
country: Netherlands
facility: University Hospital Rotterdam
city: Oslo
country: Norway
facility: Rikshospitalet Universitetsklinikk
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Barrier Therapeutics/ Stiefel, a GSK Company
name: Koen van Rossem, MD, PhD
role: STUDY_DIRECTOR
References:
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.
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.
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. doi: 10.1016/0006-2952(94)90137-6.
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. doi: 10.1111/1523-1747.ep12329579.
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. doi: 10.1111/j.1365-2133.1995.tb02672.x.
citation: 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. doi: 10.1046/j.1365-2133.2000.03884.x.
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. doi: 10.1046/j.1365-2133.2001.04411.x.
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.
citation: Vahlquist A, Blockhuys S, Steijlen P, van Rossem K, Didona B, Blanco D, Traupe H. Oral liarozole in the treatment of patients with moderate/severe lamellar ichthyosis: results of a randomized, double-blind, multinational, placebo-controlled phase II/III trial. Br J Dermatol. 2014 Jan;170(1):173-81. doi: 10.1111/bjd.12626.