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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00817063
Other study ID # 117183
Secondary ID BAP01346
Status Completed
Phase Phase 3
First received
Last updated
Start date January 8, 2009
Est. completion date April 26, 2012

Study information

Verified date April 2020
Source GlaxoSmithKline
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to investigate the safety and efficacy of alitretinoin in the treatment of severe chronic hand eczema that does not respond to treatment with potent topical steroids.


Description:

Chronic hand eczema (CHE)is a distressing disease that poses difficult problems for dermatologists. CHE leads to considerable work-absenteeism, disability and exclusion from labour market. Conventional treatments, including highly potent topical steroids, yield often unsatisfactory results. This study investigates the efficacy and safety of oral alitretinoin, a retinoid, in patients who have not responded to avoidance of causative factors, such as contact allergens and skin irritants, non-medicated skin care and highly potent topical steroids. Eligible patients are randomly assigned to receive alitretinoin or a placebo.


Recruitment information / eligibility

Status Completed
Enrollment 599
Est. completion date April 26, 2012
Est. primary completion date April 26, 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria:

- all types of chronic hand eczema, lasting for at least 6 months since initial diagnosis

- rated as severe by the physician

- unresponsive to highly potent topical corticosteroids, such as clobetasol

Exclusion Criteria:

- patients whose disease is adequately controlled by standard non-medicated therapy, including potent topical steroids, skin moisturizers, and avoidance of allergens and irritants

- patients with known allergens and irritants, who have not made a reasonable effort to avoid the substances

- patients with psoriasis lesions

- active fungal, bacterial or viral infections of the hands

- female patients who are pregnant or breastfeeding

- female patients of childbearing potential who cannot use or will not commit to use two effective methods of contraception

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
alitretinoin
Patients receive alitretinoin 30mg one capsule daily for up to 24 weeks
Placebo
Patients receive matching placebo for up to 24 weeks

Locations

Country Name City State
United States Academy of Clinical Research Arlington Texas
United States Michael Bukhalo MD Arlington Heights Illinois
United States Dermassociates, Ltd Belleville Illinois
United States Dermatology and Laser Center NW Bellingham Washington
United States University of Alabama, Birmingham Birmingham Alabama
United States Fletcher Allen Health Care Burlington Vermont
United States University of North Carolina, Dermatology Department Chapel Hill North Carolina
United States Bernstein Clinical Research Center Cincinnati Ohio
United States Modern Research Associates Dallas Texas
United States MAPS Applied Research Center Edina Minnesota
United States Shahram Jacobs, MD, Inc. Encino California
United States Deaconess Clinic, Inc. Evansville Indiana
United States Hamzavi Dermatology Clinic Fort Gratiot Michigan
United States Johnson Dermatology Fort Smith Arkansas
United States Minnesota Clinical Studies Research Center Fridley Minnesota
United States Silverton Skin Institute Grand Blanc Michigan
United States Center for Clinical Studies Houston Texas
United States Indiana University Dermatology Indianapolis Indiana
United States Dermatology Associates of Kingsport Kingsport Tennessee
United States University of California, San Diego Dermatology Clinical Trials Unit La Jolla California
United States Dartmouth-Hitchcock Medical Center Lebanon New Hampshire
United States South Lincoln Dermatology Lincoln Nebraska
United States Dermatology Research of Arkansas Little Rock Arkansas
United States Longmont Clinic, P.C. Longmont Colorado
United States Dermatology Research Associates Los Angeles California
United States Derm Research, PLLC Louisville Kentucky
United States Dermatology Specialists Louisville Kentucky
United States Madison Skin & Research Inc. Madison Wisconsin
United States Laser and Dermatology Center Marina Del Rey California
United States Saltzer Medical Group Nampa Idaho
United States Tennessee Clinical Research Center Nashville Tennessee
United States The Dermatology Center New Albany Indiana
United States Tulane University Health Sciences, Dermatology Dept New Orleans Louisiana
United States Mount Sinai School of Medicine Clinical Dermatology New York New York
United States St.Luke's/Roosevelt Hospital Center New York New York
United States Virginia Clinical Research Inc. Norfolk Virginia
United States Park Avenue Dermatology, PA Orange Park Florida
United States Kansas City Dermatology, PA Overland Park Kansas
United States Paddington Testing Co.Inc Philadelphia Pennsylvania
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States Dermatology Center of Indiana/Indiana Clinical Trials Center Plainfield Indiana
United States Oregon Dermatology and Research Center Portland Oregon
United States Oregon Health and Science University Portland Oregon
United States Rhode Island Hospital Providence Rhode Island
United States Integrated Research Group Riverside California
United States Helendale Dermatology and Medical Spa Rochester New York
United States Hull Dermatology Rogers Arkansas
United States University of California, Davis Sacramento California
United States Washington University Dermatology Research Saint Louis Missouri
United States Dermatology Clinical Research Center of San Antonio San Antonio Texas
United States Therapeutics Clinical Research San Diego California
United States East Bay Psoriasis Treatment Center San Ramon California
United States Schaumburg Dermatology Schaumburg Illinois
United States Premier Clinical Research Seattle Washington
United States American Dermatology Association Shawnee Mission Kansas
United States UMDNJ - Robert Wood Johnson School of Medicine, Dermatology Somerset New Jersey
United States Stanford University Dept of Dermatology Stanford California
United States Derm Research Center of New York Inc. Stony Brook New York
United States Toccoa Clinic Medical Associates Toccoa Georgia
United States Kansas Medical Clinic Topeka Kansas
United States Radiant Research Inc. Tucson Arizona
United States Solano Clinical Research, Dow Pharmaceutical Sciences Vallejo California
United States Grekin Skin Institute Warren Michigan
United States George Washington University - Medical Faculty Associates Washington District of Columbia
United States Center for Clinical Studies Webster Texas
United States Dundee Dermatology West Dundee Illinois
United States Palm Beach Research Center West Palm Beach Florida
United States Western State Clinical Research Inc. Wheat Ridge Colorado
United States Azalea Research Center Wilmington North Carolina
United States Wake Forrest University School of Medicine Winston-Salem North Carolina

Sponsors (2)

Lead Sponsor Collaborator
Stiefel, a GSK Company Basilea Pharmaceutica

Country where clinical trial is conducted

United States, 

References & Publications (3)

Diepgen TL, Agner T, Aberer W, Berth-Jones J, Cambazard F, Elsner P, McFadden J, Coenraads PJ. Management of chronic hand eczema. Contact Dermatitis. 2007 Oct;57(4):203-10. Review. — View Citation

Ruzicka T, Larsen FG, Galewicz D, Horváth A, Coenraads PJ, Thestrup-Pedersen K, Ortonne JP, Zouboulis CC, Harsch M, Brown TC, Zultak M. Oral alitretinoin (9-cis-retinoic acid) therapy for chronic hand dermatitis in patients refractory to standard therapy: results of a randomized, double-blind, placebo-controlled, multicenter trial. Arch Dermatol. 2004 Dec;140(12):1453-9. — View Citation

Ruzicka T, Lynde CW, Jemec GB, Diepgen T, Berth-Jones J, Coenraads PJ, Kaszuba A, Bissonnette R, Varjonen E, Holló P, Cambazard F, Lahfa M, Elsner P, Nyberg F, Svensson A, Brown TC, Harsch M, Maares J. Efficacy and safety of oral alitretinoin (9-cis retinoic acid) in patients with severe chronic hand eczema refractory to topical corticosteroids: results of a randomized, double-blind, placebo-controlled, multicentre trial. Br J Dermatol. 2008 Apr;158(4):808-17. doi: 10.1111/j.1365-2133.2008.08487.x. Epub 2008 Feb 21. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants Who Responded as Per Physician's Global Assessment (PGA) at Week 24 The investigator assigned PGA grades according to a 5-point scale (clear [not detectable], almost clear [less than 10% of affected hand surface], mild disease [less than 10% of affected hand surface], moderate disease [10% to 30% of affected hand surface], severe disease [>30% of affected hand surface]). PGA ratings were based on an integrated clinical picture of signs, symptoms, and the extent of disease. Symptoms included erythema, scaling, hyperkeratosis/lichenification, vesiculation, edema, fissures, and pruritus/pain. The PGA scale ranges from 0 (no symptom) to 4 (severe disease). Participants were considered as responders when they had a PGA of clear or almost clear. Week 24 (end-of-treatment)
Secondary Percentage Change From Baseline in Modified Total Lesion Symptom Score (mTLSS) at the End-of-treatment A 4-point scale (0=none, 1=mild, 2=moderate, 3=severe) was used to grade 7 signs or symptoms of CHE. The mTLSS was calculated as sum of assigned scores for the symptoms of erythema, scaling, lichenification/hyperkeratosis, vesiculation, edema, fissures and Pruritus/Pain. The total score ranged from 0 (best) to 21 (worst). Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-baseline values. Percentage change from Baseline = (change from Baseline / Baseline value) * 100. Data for Week 24 last observation carried forward (LOCF) has been presented. Baseline (Week 0) and Week 24 (end-of-treatment)
Secondary Number of Participants Who Responded as Per Patient Global Assessment (PaGA) at End-of-treatment At Week 24 or at the end-of-treatment participants were asked by the investigator to grade their overall change from Baseline by selecting one of the following descriptions, which best matched their perception of overall treatment effect: cleared or almost cleared (at least 90% clearing), marked improvement (at least 75% clearing), moderate improvement (at least 50% clearing), mild improvement (at least 25% clearing), no change and worsening. Participants were considered as responders when the PaGa was cleared or almost cleared. Week 24 (end-of-treatment)
Secondary Percentage Change From Baseline in Extent of Disease at End-of-treatment The extent of disease was estimated as the percentage of hand area (with 100% defined as the palmar and dorsal aspects) affected by eczema at Baseline, and at the end of treatment). Extent of disease was estimated separately for the left and right hands, and the overall extent of disease for both hands was calculated as (Left+Right)/2. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-baseline values. Percentage change from Baseline = (change from Baseline / Baseline value) * 100. Baseline (Week 0) and Week 24 (end-of-treatment)
Secondary Response Duration for Responding Participants at the End-of-therapy Response Duration was defined as time from the end-of-therapy to the first diagnosis of mild, moderate, or severe CHE. Median and inter-quartile range has been presented. Up to 72 Weeks (including 24 weeks of treatment and 48 weeks of follow-up)
Secondary Time to Relapse for Responding Participants at the End-of-therapy Time to relapse was defined as the time from end-of-therapy to the first diagnosis of severe CHE. Median and inter-quartile range has been presented. The median was based on the very last participant having a follow-up period longer than expected, those explaining the high median. Up to 72 Weeks (including 24 weeks of treatment and 48 weeks of follow-up)
Secondary Time to Response for Responding Participants at End-of-therapy Time to response was defined as time from start of treatment to first PGA assessment of "clear" or "almost clear". Median and inter-quartile range has been presented. Up to 72 Weeks (including 24 weeks of treatment and 48 weeks of follow-up)
Secondary Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During the Treatment Period An AE was defined as any adverse change from the participant's Baseline (pretreatment) clinical condition, including intercurrent illness, which occurred during the course of the clinical study after written informed consent had been given, whether considered related to treatment or not. A treatment-emergent AE was defined as any adverse change that occurred after treatment started and up to 7 days after last treatment. An SAE was any experience that suggested a significant hazard, contradiction, side effect or precaution. It was any adverse event that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. Up to Week 24 (end-of-treatment)
Secondary Number of Participants With Maximum Post Baseline Laboratory Values Outside the Marked Reference Range Blood samples were collected for the assessment of laboratory parameters hemoglobin, hematocrit, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin concentration, reticulocytes, platelets, white blood cell, lymphocytes, neutrophils, monocytes, eosinophils, basophils, total bilirubin, bilirubin conjugated (direct), aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), alkaline phosphatase (ALP), total protein, serum albumin, glucose, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, sodium, potassium, chloride, serum calcium, serum phosphate, serum creatinine, blood urea nitrogen (BUN)/urea, uric acid, Free thyroxin and thyroid stimulating hormone (TSH) at Baseline and every 4 weeks of treatment period and Week 28 of follow up period. Data for participants with values outside the marked reference range are reported. Up to Week 28
Secondary Number of Participants Referred or Not Referred to a Psychiatrist as Per Brief Summary Inventory (BSI) 53 Questionnaire up to 24 Weeks The BSI is a 53 item self-report scale used to measure nine primary symptom dimensions (somatization, obsessive-compulsive behavior, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism). Respondents rank each feeling item (e.g., "your feelings being easily hurt") on a 5-point scale where, 0=not at all, 1=a little bit, 2=moderately, 3=quite a bit, 4=extremely (0 indicates best outcome and 4 indicates worst outcome). The total score ranged from 0 (best outcome) to 212 (worse outcome). Participants with an increase above Baseline of 25% or more on any domain subscore in BSI-53, or with an increase above Baseline of >=2 points or a score >=3 on any BSI-53 item that reflects depression, suicidality, psychotic symptoms, and hostility/aggression, were to be referred to a psychiatrist within 2 weeks. Up to Week 24
Secondary Change From Baseline in Patient Health Questionnaire (PHQ-9) Score Over 28 Weeks The PHQ-9 was a standardized tests of mood/depression. This was a nine item measure with a response for each item between 0-3 where, 0=not at all, 1= several days, 2= more than half the days, 3= nearly every day. Total scores on this measure range from 0-27, with 0 being a minimum indicating no depressive symptoms, and 27 being the maximum number and severity of depressive symptoms. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-baseline values. Baseline (Week 0) and Week 4, 8, 12, 16, 20, 24, 28
Secondary Number of Participants Meeting the Referral Criteria of Psychiatric Evaluation Over 28 Weeks Participants meeting any of the following criteria were to be referred for specialist psychiatric evaluation within 2 weeks: PHQ-9 Score >=15, Two Subsequent Scores of >=10 and PHQ-9 Question 9 >=1. The PHQ -9 was a standardized tests of mood/depression. This was a nine item measure with a response for each item between 0-3 where, 0=not at all, 1= several days, 2= more than half the days, 3= nearly everyday. Total scores on this measure range from 0-27, with 0 being a minimum indicating no depressive symptoms, and 27 being the maximum number and severity of depressive symptoms. Only categories with data available at the indicated time points have been presented. Categories with null values for all the arms have not been presented. Up to 28 Weeks
Secondary Change From Baseline in Hearing Handicap Inventory for the Elderly-Screening (HHIE-S) Over 24 Weeks HHIE-S assessed participants by handicap category: no handicap (0 to 8 points); mild/moderate handicap (10 to 24 points); severe handicap (26-40 points). Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-baseline values. Baseline (Week 0) and Week 4, 8, 12, 16, 20, 24
Secondary Change From Baseline in Dizziness Handicap Inventory (DHI) Over 24 Weeks DHI assessed participants by handicap category: no handicap (0 to 14 points); mild handicap (16 to 34 points); moderate handicap (36 to 52 points); severe handicap (54 points). Increase from Baseline of <6 points, 6 to <12 points and 12 points. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-baseline values. Baseline (Week 0) and Week 4, 8, 12, 16, 20, 24
Secondary Number of Participants Responding to Tinnitus Ototoxicity Monitoring Interview (TOMI) Questionnaire Over 24 Weeks Participants who developed tinnitus were monitored by use of the TOMI. The numbers of participants with pre-existing tinnitus, new tinnitus, increased/decreased loudness of tinnitus, or increased/decreased duration of tinnitus, pulsing quality of tinnitus were assessed. Up to Week 24
Secondary Percent Change From Baseline in Bone Mineral Density (BMD) by Dual Energy X-ray Absorptiometry (DXA) Over 72 Weeks Bone mineral density scans of the left proximal femur (total hip) and anterior-posterior lumbar spine were obtained by use of DXA, at Baseline, at end of therapy, and 1 year (48 weeks) after end of therapy. In case of abnormality or surgery of the left hip, the right hip was to be used. If both hips were affected, the participant was not eligible for DXA. Vertebrae L1 to L4 had to be completely scanned. At least 3 vertebrae had to be free of any abnormalities potentially interfering with DXA analysis (eg, fractures, large osteophytes), otherwise the participant was not eligible for DXA. Baseline was defined at Week 0. Change from Baseline was calculated by subtracting the Baseline value from the individual post-baseline values. Percentage change from Baseline = (change from Baseline / Baseline value) * 100. Least square means and 95% confidence interval has been presented. Baseline (Week 0) and Week 72
Secondary Number of Participants With Adequecy of Images Assessed by X-ray Evaluation of Bones X-ray evaluations was done at Baseline (Week 0), end of therapy and at follow up period (Week 72). X-ray evaluations was done for Lateral C-Spine, Lateral T-Spine and Calcaneous. The images were evaluated as optimal, readable (but not optimal) or not readable. Up to Week 72
Secondary Number of Participants With Adverse Ophthalmological Change as Assessed by Fundus Photography - Intraocular Pressure An adverse change was defined as a change from normal at Baseline to abnormal at end of therapy, or as a worsening from Baseline for either or both eyes. A missing adverse change was defined as missing results at Baseline and end of therapy, or missing result at Baseline and abnormal at end of therapy, or normal at Baseline and missing result at end of therapy, or abnormal at Baseline and missing result at end of therapy, for both eyes or one eye when the other eye was not concerned by an adverse change. Other changes from Baseline to end of therapy was considered as no adverse change. Optic disc, macula, and retinal periphery were assessed by fundoscopy after pupil dilation using tropicamide. Up to Week 24
Secondary Number of Participants With Adverse Audiological Change as Assessed by Puretone Audiogram at Highest Frequency An adverse change was defined as a change from normal at Baseline to abnormal at end of therapy. A missing adverse change was defined as missing results at Baseline and end of therapy, or missing result at Baseline and abnormal at end of therapy, or normal at Baseline and missing result at end of therapy. Other changes from Baseline to end of therapy are considered as no adverse change. All puretone testing used a modified Hughson-Westlake procedure with 5 decibel (dB) step size. Up to Week 24
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