Plaque Psoriasis, Psoriasis
Conditions
Keywords
Psoriasis, Skin Diseases, Halobetasol, Vasoconstrictor Agents, Therapeutic Uses, Pharmacologic Actions, Anti-Inflammatory Agents, Physiological Effects of Drugs
Brief summary
This is a double-blind, multicenter, vehicle-controlled, parallel group comparison study to determine and compare the efficacy and safety of HBP Lotion 0.05% and Vehicle Lotion applied twice daily for two weeks in subjects with moderate to severe plaque psoriasis. Eligible subjects will be randomized (1:1) to one of two treatment groups - HBP Lotion 0.05% or Vehicle Lotion. The maximum amount of test article to be applied per week should not exceed 50 grams.
Interventions
DRUGHalobetasol Propionate Lotion 0.05%
Apply twice daily for 1-2 weeks, not to exceed 50 grams per week
DRUGPlacebo
Sponsors
Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject is Male or non-pregnant female; 18 years of age at time of Screening. 2. Subject is willing and able to give written informed consent. 3. subject is willing and able to apply the test article(s) as directed, comply with study instructions and commit to all follow-up visits for the duration of the study. 4. Subject has a clinical diagnosis of stable plaque psoriasis involving a minimum of 2% and no more than approximately 10% body surface area (BSA) (excluding the face, scalp, groin, axillae and other intertriginous areas). 5. Subject has an Overall Disease Severity (ODS) score for the Treatment Area of at least three (3) at the Baseline Visit. 6. If subject is a woman of childbearing potential (WOCBP) , she must have a negative urine pregnancy test (UPT) and agree to use an effective form of birth control for the duration of the study (i.e., abstinence, stabilized on hormonal contraceptives \[oral, injectable, transdermal or intravaginal\] or IUD for at least three months prior to test article application, condom and a spermicidal, or diaphragm and a spermicidal). Abstinence is an acceptable form of birth control for subjects who are not sexually active. Subjects who become sexually active during the trial must agree to use an effective form of birth control for the duration of the study.
Exclusion criteria
1. Subject has spontaneously improving or rapidly deteriorating plaque psoriasis. 2. Subject has guttate, pustular, erythrodermic or other non-plaque forms of psoriasis. 3. Subject has a physical condition which, in the investigator's opinion, might impair evaluation of plaque psoriasis, or which exposes the subject to an unacceptable risk by study participation. 4. Subject has used any phototherapy (including laser), photo-chemotherapy or systemic corticosteroid therapy (such as systemic corticosteroids \[including intralesional, intra-articular, and intramuscular corticosteroids\]) within 30 days prior to the Baseline Visit. 5. Subject has used any systemic methotrexate, retinoids, cyclosporine or analogous products within 90 days prior to the Baseline Visit. 6. Subject has used any systemic biologic therapy (i.e., FDA approved or experimental therapy) within five (5) half-lives of the biologic prior to the Baseline Visit. Published or documented half-life of the product provided by the commercial supplier or Sponsor should be used to establish this value. 7. Subject had prolonged exposure to natural or artificial sources of ultraviolet radiation within 30 days prior to the Baseline Visit or is intending to have such exposure during the study that is thought by the investigator likely to modify the subject's disease. 8. Subject has used topical body (excluding the scalp) psoriasis therapy including coal tar, anthralin, steroids, retinoids, vitamin D analogs (e.g., Dovonex®) within 14 days prior to the Baseline Visit. 9. Subject has used emollients/moisturizers on areas to be treated within four hours prior to clinical evaluation at the Baseline Visit. 10. Subject is currently using lithium or Plaquenil (hydroxychloroquine). 11. Subject is currently using a beta-blocking medication (e.g., propanolol) or angiotensin converting enzyme (ACE) inhibitor at a dose that has not been stabilized, in the opinion of the investigator. 12. Subject has a history of sensitivity to any of the ingredients in the test article. 13. Subject is pregnant, lactating, or is planning to become pregnant during the study. 14. Subject is currently enrolled in an investigational drug or device study. 15. Subject has used an investigational drug or investigational device treatment within 30 days prior to the Baseline Visit. 16. Subject has been previously enrolled in this study and treated with a test article. 17. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Disease Severity Score (Success) | Day 15 | Overall disease severity (ODS) will be recorded at baseline, Day 8, and Day 15 on a 0 (clear) to 4 (severe/very severe) point scale. The primary efficacy endpoint was the percentage of subjects with ODS treatment success at end of treatment (Day 15). Success was defined as a grade of 0 or 1 on the ODS scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Body Surface Area | Baseline, Days 8 and 15 | Changes in percent BSA with active psoriasis in the Treatment Area |
| Clinical Signs and Symptoms of Psoriasis | Days 8 and 15 | The proportion of subjects rated a treatment success for each of the clinical signs and symptoms of psoriasis: scaling, erythema, plaque elevation and pruritis. Treatment success is defined as a score of 0 or 1 on a five-point scale ranging from 0 = clear to 4 = severe/very severe. |
| Overall Disease Severity Score (Improvement) | Days 8 and 15 | The proportion of subjects rated a improved for ODS at Day 8 and Day 15. Improvement is defined as at least a two (2) grade decrease in severity score relative to baseline using a five-point scale ranging from 0 = clear to 4 = severe/very severe. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: November 2011 to February 2012 The location of clinical sites included dermatology clinical research centers.
Pre-assignment details
All subjects who met the entry criteria were randomized and enrolled into the study.
Participants by arm
| Arm | Count |
|---|---|
| Halobetasol Propionate Lotion 0.05% Topical lotion, applied twice daily
Halobetasol Propionate Lotion 0.05%: Apply twice daily for 1-2 weeks, not to exceed 50 grams per week | 36 |
| Vehicle Lotion Topical lotion, applied twice daily
Placebo | 36 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Vehicle Lotion | Halobetasol Propionate Lotion 0.05% |
|---|---|---|---|
| Age, Continuous | 51.2 years STANDARD_DEVIATION 12.38 | 52.3 years STANDARD_DEVIATION 13.06 | 50.0 years STANDARD_DEVIATION 11.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 3 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 33 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Overall Disease Severity at Baseline Almost clear | 0 participants | 0 participants | 0 participants |
| Overall Disease Severity at Baseline Clear | 0 participants | 0 participants | 0 participants |
| Overall Disease Severity at Baseline Mild | 0 participants | 0 participants | 0 participants |
| Overall Disease Severity at Baseline Moderate | 61 participants | 31 participants | 30 participants |
| Overall Disease Severity at Baseline Severe/very severe | 11 participants | 5 participants | 6 participants |
| Percent BSA to be Treated at Baseline | 3.8 %BSA STANDARD_DEVIATION 1.88 | 4.0 %BSA STANDARD_DEVIATION 2.04 | 3.7 %BSA STANDARD_DEVIATION 1.74 |
| Pruritus at Baseline Mild | 19 participants | 5 participants | 14 participants |
| Pruritus at Baseline Mild to moderate | 23 participants | 11 participants | 12 participants |
| Pruritus at Baseline Moderal to severe | 6 participants | 5 participants | 1 participants |
| Pruritus at Baseline Moderate | 10 participants | 5 participants | 5 participants |
| Pruritus at Baseline None | 11 participants | 8 participants | 3 participants |
| Pruritus at Baseline Severe | 3 participants | 2 participants | 1 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 66 Participants | 34 Participants | 32 Participants |
| Sex: Female, Male Female | 19 Participants | 11 Participants | 8 Participants |
| Sex: Female, Male Male | 53 Participants | 25 Participants | 28 Participants |
| Signs of Psoriasis at Baseline (erythema) Almost clear | 1 participants | 0 participants | 1 participants |
| Signs of Psoriasis at Baseline (erythema) Clear | 0 participants | 0 participants | 0 participants |
| Signs of Psoriasis at Baseline (erythema) Mild | 2 participants | 1 participants | 1 participants |
| Signs of Psoriasis at Baseline (erythema) Moderate | 46 participants | 24 participants | 22 participants |
| Signs of Psoriasis at Baseline (erythema) Severe/very severe | 23 participants | 11 participants | 12 participants |
| Signs of Psoriasis at Baseline (plaque elevation) Almost clear | 0 participants | 0 participants | 0 participants |
| Signs of Psoriasis at Baseline (plaque elevation) Clear | 0 participants | 0 participants | 0 participants |
| Signs of Psoriasis at Baseline (plaque elevation) Mild | 5 participants | 3 participants | 2 participants |
| Signs of Psoriasis at Baseline (plaque elevation) Moderate | 58 participants | 28 participants | 30 participants |
| Signs of Psoriasis at Baseline (plaque elevation) Severe/very severe | 9 participants | 5 participants | 4 participants |
| Signs of Psoriasis at Baseline (scaling) Almost clear | 0 participants | 0 participants | 0 participants |
| Signs of Psoriasis at Baseline (scaling) Clear | 0 participants | 0 participants | 0 participants |
| Signs of Psoriasis at Baseline (scaling) Mild | 8 participants | 2 participants | 6 participants |
| Signs of Psoriasis at Baseline (scaling) Moderate | 50 participants | 28 participants | 22 participants |
| Signs of Psoriasis at Baseline (scaling) Severe/very severe | 14 participants | 6 participants | 8 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 36 | 5 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
Overall Disease Severity Score (Success)
Overall disease severity (ODS) will be recorded at baseline, Day 8, and Day 15 on a 0 (clear) to 4 (severe/very severe) point scale. The primary efficacy endpoint was the percentage of subjects with ODS treatment success at end of treatment (Day 15). Success was defined as a grade of 0 or 1 on the ODS scale.
Time frame: Day 15
Population: Analysis shown is the Intent-to-treat (ITT) population, defined as all enrolled participants who were randomized and applied at least one dose of the test article.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Halobetasol Propionate Lotion 0.05% | Overall Disease Severity Score (Success) | 30.6 percentage of participants |
| Vehicle Lotion | Overall Disease Severity Score (Success) | 0.0 percentage of participants |
p-value: <0.001Fisher Exact
Secondary
Clinical Signs and Symptoms of Psoriasis
The proportion of subjects rated a treatment success for each of the clinical signs and symptoms of psoriasis: scaling, erythema, plaque elevation and pruritis. Treatment success is defined as a score of 0 or 1 on a five-point scale ranging from 0 = clear to 4 = severe/very severe.
Time frame: Days 8 and 15
Population: Analysis shown is based on the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Halobetasol Propionate Lotion 0.05% | Clinical Signs and Symptoms of Psoriasis | Erythema (Day 15) | 13.9 percentage of participants |
| Halobetasol Propionate Lotion 0.05% | Clinical Signs and Symptoms of Psoriasis | Scaling (Day 8) | 25.0 percentage of participants |
| Halobetasol Propionate Lotion 0.05% | Clinical Signs and Symptoms of Psoriasis | Scaling (Day 15) | 61.1 percentage of participants |
| Halobetasol Propionate Lotion 0.05% | Clinical Signs and Symptoms of Psoriasis | Erythema (Day 8) | 2.9 percentage of participants |
| Halobetasol Propionate Lotion 0.05% | Clinical Signs and Symptoms of Psoriasis | Plaque elevation (Day 8) | 11.1 percentage of participants |
| Halobetasol Propionate Lotion 0.05% | Clinical Signs and Symptoms of Psoriasis | Plaque elevation (Day 15) | 38.9 percentage of participants |
| Vehicle Lotion | Clinical Signs and Symptoms of Psoriasis | Plaque elevation (Day 8) | 0.0 percentage of participants |
| Vehicle Lotion | Clinical Signs and Symptoms of Psoriasis | Erythema (Day 15) | 2.9 percentage of participants |
| Vehicle Lotion | Clinical Signs and Symptoms of Psoriasis | Erythema (Day 8) | 0.0 percentage of participants |
| Vehicle Lotion | Clinical Signs and Symptoms of Psoriasis | Scaling (Day 8) | 8.6 percentage of participants |
| Vehicle Lotion | Clinical Signs and Symptoms of Psoriasis | Plaque elevation (Day 15) | 2.9 percentage of participants |
| Vehicle Lotion | Clinical Signs and Symptoms of Psoriasis | Scaling (Day 15) | 11.4 percentage of participants |
Secondary
Overall Disease Severity Score (Improvement)
The proportion of subjects rated a improved for ODS at Day 8 and Day 15. Improvement is defined as at least a two (2) grade decrease in severity score relative to baseline using a five-point scale ranging from 0 = clear to 4 = severe/very severe.
Time frame: Days 8 and 15
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Halobetasol Propionate Lotion 0.05% | Overall Disease Severity Score (Improvement) | at Day 8 | 13.9 percentage of participants |
| Halobetasol Propionate Lotion 0.05% | Overall Disease Severity Score (Improvement) | at Day 15 | 44.4 percentage of participants |
| Vehicle Lotion | Overall Disease Severity Score (Improvement) | at Day 8 | 0.0 percentage of participants |
| Vehicle Lotion | Overall Disease Severity Score (Improvement) | at Day 15 | 0.0 percentage of participants |
Secondary
Percent Body Surface Area
Changes in percent BSA with active psoriasis in the Treatment Area
Time frame: Baseline, Days 8 and 15
Population: Analysis shown is based on the ITT population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Halobetasol Propionate Lotion 0.05% | Percent Body Surface Area | at Day 8 | -0.3 Change in %BSA | Standard Deviation 0.57 |
| Halobetasol Propionate Lotion 0.05% | Percent Body Surface Area | at Day 15 | -1.3 Change in %BSA | Standard Deviation 1.34 |
| Vehicle Lotion | Percent Body Surface Area | at Day 8 | -0.1 Change in %BSA | Standard Deviation 0.34 |
| Vehicle Lotion | Percent Body Surface Area | at Day 15 | -0.2 Change in %BSA | Standard Deviation 0.93 |