Blinded Study of Topical Investigational Lotion Vs. Approved Cream in Treatment of Plaque Psoriasis

• Sponsor: Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01166646
• Collaborator: (none)
• Enrollment: 43
• Locations: 5
• Arms: 2
• Duration (Months): 12
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis	Drug: Halobetasol Proprionate Lotion 0.05%; Drug: Halobetasol Proprionate Cream 0.05%	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Halobetasol Proprionate Lotion 0.05% Subjects randomized to receive lotion	Drug: Halobetasol Proprionate Lotion 0.05%; Apply 3.5 grams twice daily for 1-2 weeks
Active Comparator: Halobetasol Proprionate Cream 0.05% Subjects randomized to receive cream	Drug: Halobetasol Proprionate Cream 0.05%; Apply 3.5 grams twice daily for 1-2 weeks; Other Names: Ultravate

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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 Outcome Measures

1. 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).

2. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Therapeutics Clinical Research	San Diego	California	United States	92123
2	Michigan Center for Skin Care Research (dba Skin Care Research)	Clinton Township	Michigan	United States	48038
3	Somerset Skin Centre	Troy	Michigan	United States	48084
4	Dermatology, Laser & Vein Specialists of the Carolinas PLLC	Charlotte	North Carolina	United States	28207
5	DermResearch Inc.	Austin	Texas	United States	78759

Sponsors and Collaborators

• Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT01166646
• Other Study ID Numbers: 000-0551-202
• First Posted: Jul 21, 2010
• Last Update Posted: May 16, 2016
• Last Verified: Apr 1, 2016

• Additional relevant MeSH terms: Psoriasis; Clobetasol; Halobetasol

Study Results

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 Detail	All subjects who met the entry criteria were randomized and enrolled into the study.

Arm/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks
Period Title: Overall Study
STARTED	21	22
COMPLETED	20	21
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%	Total
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Total of all reporting groups
Overall Participants	21	22	43
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.5 (9.28)	47.7 (12.57)	48.5 (11.00)
Sex: Female, Male (Count of Participants)
Female	8 38.1%	7 31.8%	15 34.9%
Male	13 61.9%	15 68.2%	28 65.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.5%	5 22.7%	7 16.3%
Not Hispanic or Latino	19 90.5%	17 77.3%	36 83.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 4.5%	1 2.3%
Native Hawaiian or Other Pacific Islander	1 4.8%	0 0%	1 2.3%
Black or African American	3 14.3%	1 4.5%	4 9.3%
White	16 76.2%	20 90.9%	36 83.7%
More than one race	1 4.8%	0 0%	1 2.3%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Adrenal Suppression Potential
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks
Measure Participants	21	21
Normal	16 76.2%	18 81.8%
Abnormal	5 23.8%	3 13.6%

2. Primary Outcome

Title	Pharmacokinetic Properties (Cmax)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic properties were evaluated in a subgroup of 12 adult subjects per arm.

Arm/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	145.9 (106.9)	136.2 (71.44)

3. Primary Outcome

Title	Pharmacokinetic Properties (Tmax)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic properties were evaluated in a subgroup of 12 adult subjects per arm.

Arm/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks
Measure Participants	12	12
Geometric Mean (Full Range) [Hours]	3	3

4. Primary Outcome

Title	Pharmacokinetic Properties (AUC)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetics properties were evaluated in a subgroup of 12 adult subjects per arm.

Arm/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks
Measure Participants	12	12
Geometric Mean (Geometric Coefficient of Variation) [pg*h/mL]	1267.7 (89.84)	1229.8 (67.19)

5. Secondary Outcome

Title	Changes in Disease Severity (Success)
Description	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

Outcome Measure Data

Analysis Population Description

Analysis shown is based on the ITT population at Day 15.

Arm/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks
Measure Participants	21	22
Number [participants]	1 4.8%	5 22.7%

6. Secondary Outcome

Title	Number of Subjects Whose Signs of Psoriasis Was Designated "Success"
Description	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

Outcome Measure Data

Analysis Population Description

Analysis shown is based on the number of subjects whose Signs of Psoriasis was designated "Success" (ITT population) at Day 15.

Arm/Group Title	Halobetasol Proprionate Lotion 0.05%	Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for up to 2 weeks	Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for up to 2 weeks
Measure Participants	21	22
Scaling	6 28.6%	11 50%
Erythema	2 9.5%	6 27.3%
Plaque elevation	2 9.5%	7 31.8%

Adverse Events

Time Frame	AEs were collected from study screening (performed 14 days prior to baseline/first dose) to end of study treatment or participant termination. AEs that continued beyond completion/termination were followed until resolution or stabilization.
Adverse Event Reporting Description	The Safety population included all subjects enrolled in the study who were dispensed the test article at least once.
Arm/Group Title	Halobetasol Proprionate Lotion 0.05%		Halobetasol Proprionate Cream 0.05%
Arm/Group Description	Subjects randomized to receive lotion Halobetasol Proprionate Lotion 0.05%: Apply 3.5 grams twice daily for 1-2 weeks		Subjects randomized to receive cream Halobetasol Proprionate Cream 0.05%: Apply 3.5 grams twice daily for 1-2 weeks
All Cause Mortality
	Halobetasol Proprionate Lotion 0.05%		Halobetasol Proprionate Cream 0.05%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Halobetasol Proprionate Lotion 0.05%		Halobetasol Proprionate Cream 0.05%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Halobetasol Proprionate Lotion 0.05%		Halobetasol Proprionate Cream 0.05%
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/21 (42.9%)		8/22 (36.4%)
Endocrine disorders
Type 2 diabetes mellitus	1/21 (4.8%)	1	0/22 (0%)	0
Gastrointestinal disorders
Nausea	1/21 (4.8%)	1	1/22 (4.5%)	1
General disorders
Application site pain	1/21 (4.8%)	1	1/22 (4.5%)	1
Feeling hot	1/21 (4.8%)	1	0/22 (0%)	0
Pallor	0/21 (0%)	0	1/22 (4.5%)	1
Infections and infestations
Influenza	1/21 (4.8%)	1	0/22 (0%)	0
nasopharyngitis	1/21 (4.8%)	1	1/22 (4.5%)	1
Throat infection	1/21 (4.8%)	1	0/22 (0%)	0
Tooth infection	0/21 (0%)	0	1/22 (4.5%)	1
Upper respiratory tract infection	0/21 (0%)	0	2/22 (9.1%)	2
Injury, poisoning and procedural complications
Procedural dizziness	0/21 (0%)	0	1/22 (4.5%)	1
Procedural nausea	1/21 (4.8%)	1	0/22 (0%)	0
Procedural pain	0/21 (0%)	0	1/22 (4.5%)	1
Investigations
ACTH stimulation test abnormal	5/21 (23.8%)	5	3/22 (13.6%)	3
Renal and urinary disorders
Nephrolithiasis	1/21 (4.8%)	1	0/22 (0%)	0
Renal pain	1/21 (4.8%)	1	0/22 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/21 (4.8%)	1	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor has first right to publish pooled study data. In the event that such manuscript has not been submitted for publication within 12 months from study completion/termination at all participating sites, the PI shall have the right to single center publications provided they submit any data for presentation, oral or written, to the Sponsor for review 30 days prior to public dissemination. The PI may not disclose previously undisclosed confidential information other than study results.