Ichthyosis, LamellarPhase 2/3NCT00282724
Efficacy and Safety of Two Doses of Liarozole vs. Placebo for the Treatment of Lamellar Ichthyosis
A Phase 2/3 study testing Liarozole in people with Ichthyosis, Lamellar, run by Stiefel, a GSK Company at 16 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Ichthyosis, Lamellar
- What is being tested?
- Liarozole
- How many people
- 98 participants
- Where
- 16 sitesin 9 countries
- Study dates
- Jan 2006to Apr 2007
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
16 sites in 9 countries.
16 sites in 9 countries
Germany4 sites
Tomesa Fachklinik
Bad Salzschlirf
Dueren
Düren
Otto-von-Guericke-Universität
Magdeburg
University Hospital Muenster
Münster
Belgium2 sites
Academisch Ziekenhuis Vrije Universiteit Brussel
Brussels
Geel
Geel
Canada2 sites
Hôpital Saint-Justine
Montreal
Newlab Clinical Research Inc.
St. John's
Italy2 sites
Fondazione Policlinico Mangiagalli e Regina Elena
Milan
Istituto Dermopatico dell'Immacolata
Rome
Netherlands2 sites
Academisch Ziekenhuis Maastricht
Maastricht
University Hospital Rotterdam
Rotterdam
About this 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
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.
Read the 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.
- Conditions
- Ichthyosis, Lamellar
- Being tested
- Liarozole
- Keywords
- Lamellar ichthyosis, Liarozole, Investigator's Global Assessment, Scaling
- Medical subject headings
- Ichthyosis, Lamellar
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiarozoleDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy: Investigator's Global Assessment
Secondary outcomes (5)
Overall Scaling Score
Severity scores of other symptoms
Quality of Life
Safety and tolerability
Pharmacokinetics
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2006 (estimated)
- Study startJan 2006
- Primary completionApr 2007
- Study completionApr 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Ichthyosis, LamellarStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stiefel, a GSK Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Koen van Rossem, MD, PhD, Study director, Barrier Therapeutics/ Stiefel, a GSK Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00282724
- Sponsor's protocol ID
- BT0500INT001
- Status last verified
- Sep 2011
- First submitted
- 20 Jan 2006
- Last updated
- 26 Sep 2011
- Results posted
- No
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.
PubMed 2299598Van 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.
PubMed 1374473Van 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.
PubMed 8129749Kang 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.
PubMed 8757760Dockx 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.
PubMed 8546999Berth-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.
PubMed 11122017Bhushan 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.
PubMed 11703279Lucker 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.
PubMed 9039298Vahlquist 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.
PubMed 24102348
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00282724
- Acronym / sponsor ID
- BT0500INT001
- Conditions
- Ichthyosis, Lamellar
- Keywords
- Lamellar ichthyosis, Liarozole, Investigator's Global Assessment, Scaling
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- Stiefel, a GSK CompanyIndustry (pharma, biotech, devices)
- Study start
- Jan 2006
- Primary completion
- Apr 2007 (actual)
- Study completion
- Apr 2007 (actual)
- First posted
- 27 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liarozole | Drug | – |
Primary outcome
Efficacy: Investigator's Global Assessment
5 secondary outcomes
Overall Scaling Score
Severity scores of other symptoms
Quality of Life
Safety and tolerability
Pharmacokinetics
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2011.
- Background: PubMed 2299598Van 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.
- Background: PubMed 1374473Van 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.
- Background: PubMed 8129749Van 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.
- Background: PubMed 8757760Kang 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.
- Background: PubMed 8546999Dockx 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.
- Background: PubMed 11122017Berth-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.
- Background: PubMed 11703279Bhushan 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.
- Background: PubMed 9039298Lucker 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.
- Derived from this study: PubMed 24102348Vahlquist 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.
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Sezary Syndrome, Ichthyosis, Lamellar
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Koen van Rossem, MD, PhD study director
Barrier Therapeutics/ Stiefel, a GSK Company
16 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Liarozole in people with Ichthyosis, Lamellar, run by Stiefel, a GSK Company at 16 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Germany, Belgium, Canada, Italy, Netherlands and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy: Investigator's Global Assessment. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00282724, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2011.