Plaque Psoriasis
Conditions
Brief summary
The purpose of this study is to determine whether the investigational lotion is an effective treatment of moderate to severe plaque psoriasis in comparison to an approved cream.
Interventions
DRUGHalobetasol Proprionate Lotion 0.05%
Apply 3.5 grams twice daily for 1-2 weeks
DRUGHalobetasol Proprionate Cream 0.05%
Apply 3.5 grams twice daily for 1-2 weeks
Sponsors
Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects are male or non-pregnant female; 18 years of age at the time of screening. * Subjects provide Institutional Review Board (IRB) approved written informed consent for participating in this study. * Subjects have a clinical diagnosis of stable plaque psoriasis involving a minimum of 20% body surface area and an Overall Disease Severity (ODS) score on the designated treatment area of at least 3 as determined by the evaluating investigator. * Subjects are willing and able to apply the study medication as directed, comply with study instructions and commit to all follow-up visits for the duration of the study. * Women of childbearing potential (WOCBP) must have a negative urine pregnancy test at the Screening (Part B) and Baseline Visits and agree to use an effective form of birth control for the duration of the study (abstinence, stabilized on oral contraceptives or contraceptive patches for at least three months, implant, injection, IUD, NuvaRing®, condom and spermicidal or diaphragm and 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, non-prohibited form of birth control for the duration of the study.
Exclusion criteria
* Subjects have spontaneously improving or rapidly deteriorating plaque psoriasis, or have guttate, pustular, erythrodermic or other non-plaque forms of psoriasis. * Subjects have a physical condition which, in the Investigator's opinion, might impair evaluation of plaque psoriasis, adrenal axis function (e.g., Addison's Disease, Cushing's Syndrome) or which exposes the subject to an unacceptable risk by study participation. * Subjects have used any phototherapy (including laser), photo-chemotherapy or systemic psoriasis therapy including methotrexate, retinoids, cyclosporine or biologics within 30 days prior to the initiation of study medication treatment. * Subjects have used systemic corticosteroids (including oral or intramuscular) or topical, inhaled or intranasal corticosteroids within 30 or 14 days, respectively, prior to Part B of the Screening Visit and/or subjects have used systemic or topical corticosteroids between the Screening Visit and the initiation of treatment. * Subjects have had prolonged exposure to natural or artificial sources of ultraviolet radiation within 30 days prior to the initiation of treatment or are intending to have such exposure during the study that is thought by the Investigator to likely modify the subject's disease. * Subjects have used topical psoriatic therapy including tar, anthralin, retinoids, vitamin D analogs (e.g., Dovonex®) within 14 days prior to the initiation of study medication treatment. * Subjects have used emollients/moisturizers on areas to be treated within one day prior to the initiation of study medication treatment. * Subjects are currently using lithium or plaquenil. * Subjects are currently using a beta-blocking medication (e.g., propanolol) or angiotensin converting enzyme (ACE) inhibitors at a dose that has not been stabilized, in the opinion of the Investigator. * Subjects have a history of sensitivity to any of the ingredients in the study medication. * Subjects are pregnant, nursing or planning a pregnancy during the study period. * Subjects are currently enrolled in an investigational drug or device study. * Subjects have received an investigational drug or an investigational device within 30 days prior to screening. * Subjects have been previously enrolled in this study and treated with the study medication. * Subjects have irregular sleep schedules or work night shifts (cortisol levels exhibit physiological diurnal variation). * Subjects have a screening CST with a post 30-minute stimulation cortisol level of ≤ 18 µg/dL.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adrenal Suppression Potential | After 1-2 weeks dose | Hypothalamic Pituitary-Adrenal (HPA)-Axis responses to Cosyntropin Stimulation Testing (CST) were dichotomized to normal and abnormal. An abnormal HPA Axis response (HPA Suppression) was defined as a 30-minute post-stimulation serum cortisol level of ≤18 μg/dL at the end of treatment. |
| Pharmacokinetic Properties (Cmax) | Day 8 | Comparison of PK results (peak concentration in plasma \[Cmax\]) between the two Treatment Groups will be conducted following the last application of the medication on Day 8. |
| Pharmacokinetic Properties (Tmax) | Day 8 | Comparison of PK results (time to peak concentration \[Tmax\]) between the two Treatment Groups will be conducted following the last application of the medication on Day 8. |
| Pharmacokinetic Properties (AUC) | Day 8 | Comparison of PK results (area under the curve \[AUC\] from time 0 to infinity) between the two Treatment Groups will be conducted following the last application of the medication on Day 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Disease Severity (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. ODS evaluations will be dichotomized to success and failure with success defined as a grade of 1 or 0 at the end of treatment (EOT). |
| Number of Subjects Whose Signs of Psoriasis Was Designated Success | Day 15 | Signs of psoriasis including scaling, erythema, and plaque elevation will be recorded at baseline, Day 8, and Day 15 on a 0 (clear) to 4 (severe/very severe) point scale. Each of the signs of psoriasis will be dichotomized to a) success and failure with success defined as a grade of 1 or 0 at the End of Treatment (EOT; i.e., the visit at which psoriasis has cleared \[Day 8 or Day 15\] or end of the assigned treatment period). |
Countries
United States
Participant flow
Recruitment details
Recruitment period: August 2010 to May 2011 The location of clinical sites included private dermatology clinics and 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 Proprionate Lotion 0.05% Subjects randomized to receive lotion
Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks | 21 |
| Halobetasol Proprionate Cream 0.05% Subjects randomized to receive cream
Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks | 22 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Halobetasol Proprionate Cream 0.05% | Total | Halobetasol Proprionate Lotion 0.05% |
|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 12.57 | 48.5 years STANDARD_DEVIATION 11 | 49.5 years STANDARD_DEVIATION 9.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 7 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 36 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 36 Participants | 16 Participants |
| Sex: Female, Male Female | 7 Participants | 15 Participants | 8 Participants |
| Sex: Female, Male Male | 15 Participants | 28 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 21 | 8 / 22 |
| serious Total, serious adverse events | 0 / 21 | 0 / 22 |
Outcome results
Primary
Adrenal Suppression Potential
Hypothalamic Pituitary-Adrenal (HPA)-Axis responses to Cosyntropin Stimulation Testing (CST) were dichotomized to normal and abnormal. An abnormal HPA Axis response (HPA Suppression) was defined as a 30-minute post-stimulation serum cortisol level of ≤18 μg/dL at the end of treatment.
Time frame: After 1-2 weeks dose
Population: Analysis shown is based on the ITT population, defined as all enrolled participants who were randomized and applied at least one dose of the test article.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Halobetasol Proprionate Lotion 0.05% | Adrenal Suppression Potential | Normal | 16 participants |
| Halobetasol Proprionate Lotion 0.05% | Adrenal Suppression Potential | Abnormal | 5 participants |
| Halobetasol Proprionate Cream 0.05% | Adrenal Suppression Potential | Normal | 18 participants |
| Halobetasol Proprionate Cream 0.05% | Adrenal Suppression Potential | Abnormal | 3 participants |
Primary
Pharmacokinetic Properties (AUC)
Comparison of PK results (area under the curve \[AUC\] from time 0 to infinity) between the two Treatment Groups will be conducted following the last application of the medication on Day 8.
Time frame: Day 8
Population: Pharmacokinetics properties were evaluated in a subgroup of 12 adult subjects per arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Halobetasol Proprionate Lotion 0.05% | Pharmacokinetic Properties (AUC) | 1267.7 pg*h/mL | Geometric Coefficient of Variation 89.84 |
| Halobetasol Proprionate Cream 0.05% | Pharmacokinetic Properties (AUC) | 1229.8 pg*h/mL | Geometric Coefficient of Variation 67.19 |
Primary
Pharmacokinetic Properties (Cmax)
Comparison of PK results (peak concentration in plasma \[Cmax\]) between the two Treatment Groups will be conducted following the last application of the medication on Day 8.
Time frame: Day 8
Population: Pharmacokinetic properties were evaluated in a subgroup of 12 adult subjects per arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Halobetasol Proprionate Lotion 0.05% | Pharmacokinetic Properties (Cmax) | 145.9 pg/mL | Geometric Coefficient of Variation 106.9 |
| Halobetasol Proprionate Cream 0.05% | Pharmacokinetic Properties (Cmax) | 136.2 pg/mL | Geometric Coefficient of Variation 71.44 |
Primary
Pharmacokinetic Properties (Tmax)
Comparison of PK results (time to peak concentration \[Tmax\]) between the two Treatment Groups will be conducted following the last application of the medication on Day 8.
Time frame: Day 8
Population: Pharmacokinetic properties were evaluated in a subgroup of 12 adult subjects per arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Halobetasol Proprionate Lotion 0.05% | Pharmacokinetic Properties (Tmax) | 3 Hours |
| Halobetasol Proprionate Cream 0.05% | Pharmacokinetic Properties (Tmax) | 3 Hours |
Secondary
Changes in Disease Severity (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. ODS evaluations will be dichotomized to success and failure with success defined as a grade of 1 or 0 at the end of treatment (EOT).
Time frame: Day 15
Population: Analysis shown is based on the ITT population at Day 15.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Halobetasol Proprionate Lotion 0.05% | Changes in Disease Severity (Success) | 1 participants |
| Halobetasol Proprionate Cream 0.05% | Changes in Disease Severity (Success) | 5 participants |
Secondary
Number of Subjects Whose Signs of Psoriasis Was Designated Success
Signs of psoriasis including scaling, erythema, and plaque elevation will be recorded at baseline, Day 8, and Day 15 on a 0 (clear) to 4 (severe/very severe) point scale. Each of the signs of psoriasis will be dichotomized to a) success and failure with success defined as a grade of 1 or 0 at the End of Treatment (EOT; i.e., the visit at which psoriasis has cleared \[Day 8 or Day 15\] or end of the assigned treatment period).
Time frame: Day 15
Population: Analysis shown is based on the number of subjects whose Signs of Psoriasis was designated Success (ITT population) at Day 15.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Halobetasol Proprionate Lotion 0.05% | Number of Subjects Whose Signs of Psoriasis Was Designated Success | Scaling | 6 participants |
| Halobetasol Proprionate Lotion 0.05% | Number of Subjects Whose Signs of Psoriasis Was Designated Success | Erythema | 2 participants |
| Halobetasol Proprionate Lotion 0.05% | Number of Subjects Whose Signs of Psoriasis Was Designated Success | Plaque elevation | 2 participants |
| Halobetasol Proprionate Cream 0.05% | Number of Subjects Whose Signs of Psoriasis Was Designated Success | Scaling | 11 participants |
| Halobetasol Proprionate Cream 0.05% | Number of Subjects Whose Signs of Psoriasis Was Designated Success | Erythema | 6 participants |
| Halobetasol Proprionate Cream 0.05% | Number of Subjects Whose Signs of Psoriasis Was Designated Success | Plaque elevation | 7 participants |