A Safety and Tolerability Study of Topical PAT-001 in Congenital Ichthyosis

• Sponsor: Patagonia Pharmaceuticals, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02864082
• Collaborator: (none)
• Enrollment: 19
• Locations: 5
• Arms: 4
• Actual Duration (Months): 20.9
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Congenital ichthyosis (CI) is a large, heterogeneous family of inherited skin disorders of cornification resulting from an abnormality of skin keratinization, such as scaling and thickening of the skin. Treatment options include keratolytic agents, which can abruptly lead to extensive shedding or peeling of scales. PAT-001 primarily acts as a keratolytic agent; thus, making it a potential drug candidate for the treatment of skin disorders associated with hyperkeratinization, such as CI. The current study intends to evaluate the safety and tolerability of PAT-001 in patients with CI of either the Lamellar or X-Linked subtypes.

Condition or Disease	Intervention/Treatment	Phase
Congenital Ichthyosis	Drug: PAT-001, 0.1%; Drug: PAT-001, 0.2%; Drug: Vehicle for PAT-001 0.1%; Drug: Vehicle for PAT-001 0.2%	Phase 2

Detailed Description

The management of CI is a life-long endeavor, which remains largely symptomatic (i.e., emollients with or without keratolytics agents) and commonly focused on reducing scaling and/or skin lubrication with both systemic and topical treatments. A first-line therapy includes hydration and lubrication accomplished by creams and ointments containing low concentrations of salt, urea, or glycerol, which increase the water-binding capacity of the horny layer. Addition of keratolytics agents are used to decrease corneocyte cohesiveness, to promote desquamation, and to dissolve keratins and lipids (e.g., α-hydroxy acids, salicylic acid, high dose urea, propylene glycol, N-acetylcysteine, and retinoids). Systemic retinoid treatment is reserved for those patients refractory to topical agents because of long-term adverse effects and teratogenicity.

This is a two part, Phase 2, multicenter, proof-of-concept (POC) study of the safety and tolerability of PAT-001 for the treatment of Congenital ichthyosis (CI) in patients ages 12 years of age and older. Part 1 will be a double-blind, randomized, vehicle controlled, bilateral comparison of two treatments (PAT-001 [0.1% or 0.2%] vs. vehicle) for eight (8) weeks.

Part 2 will be a double-blind, active only treatment comparison of the two PAT-001 concentrations (0.1% or 0.2%) for an additional four (4) weeks. Subjects will have the option to participate in the pharmacokinetics (PK) portion of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Bilateral Comparison, Vehicle-Controlled, Safety and Tolerability Study of Topical PAT-001 for the Treatment of Congenital Ichthyosis
• Actual Study Start Date: Mar 8, 2017
• Actual Primary Completion Date: Feb 13, 2018
• Actual Study Completion Date: Dec 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PAT-001 0.1% Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). This comparison lasts from Weeks 0-8 Part 2: Patients will apply only PAT-001, 0.1% to both Treatment Areas from Weeks 8-12.	Drug: PAT-001, 0.1%; PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug.; Other Names: PAT-001
Experimental: PAT-001 0.2% Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). This comparison lasts from Weeks 0-8 Part 2: Patients will apply PAT-001, 0.2% to both Treatment Areas.	Drug: PAT-001, 0.2%; PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug.; Other Names: PAT-001
Placebo Comparator: Vehicle for PAT-001 0.1% arm Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). The application of vehicle only lasts from Weeks 0-8.	Drug: Vehicle for PAT-001 0.1%; Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.1%.; Other Names: Vehicle
Placebo Comparator: Vehicle for PAT-001 0.2% arm Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). The application of vehicle only lasts from Weeks 0-8.	Drug: Vehicle for PAT-001 0.2%; Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.2%.; Other Names: Vehicle

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) in Part 1 of Trial (Weeks 0-8) [Day 0 through Day 57 (Weeks 0-8)]

   The number of participants with AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported.

2. Incidence of Local Skin Reactions (LSRs) in Participants Treated With PAT-001 0.1%, 0.2% and/or Vehicle [Up to Day 84 (Weeks 0-12)]

   LSRs including burning/stinging, pain, and pruritus (itch) will be assessed in each Treatment Area using a four-point ordinal scale where 0=none, 1=mild, 2=moderate, and 3=severe (based on the investigator's evaluation of the skin reaction) at each clinic visit to allow a comparison between Treatment Groups and Test Articles. Only LSRs that require medical intervention (e.g., prescription medication) or require withholding or reduction in dosing frequency of the test articles will be documented in this LSR Table. Any LSRs that are not listed here will be recorded as AEs.

Secondary Outcome Measures

1. Number of Participants Achieving Improvement to State of Clear, Almost Clear or Mild in the Investigator's Global Assessment (IGA) Using a Five-point Scale at Day 57 (Part 1) [Up to Day 57]

   Overall severity of ichthyosis will be graded using a five-point scale Investigator Global Assessment (IGA) based upon a 5 point scale going from 0=clear., 1=almost clear, 2=mild, 3=moderate to 4=severe. Scoring is based upon investigator evaluation. This is a static morphological scale that refers to a point in time and not a comparison to Baseline.

2. Number of Participants Achieving an Improvement of at Least 1 Point Score in the Individual Clinical Signs/Symptoms of Erythema, Scaling, Fissuring and Papulation/Lichenification Using a Five-point Scale [Up to Day 57 (Weeks 0-8)]

   Overall severity of erythema (redness), scaling , fissuring (cracks in skin), and papulation/lichenification (skin thickening, increased pigmentation and/or exaggerated skin lines, formation of papules) will be graded using a five-point scale from 0=clear, 1=almost clear, 2=mild, 3=moderate to 4=severe. This is a static morphological scale that refers to a point in time and not a comparison to Baseline. This scoring is based upon investigator discretion.

Other Outcome Measures

1. Pharmacokinetics of PAT-001 0.1% and 0.2% at Different Timepoints [Day 1 (0,1, 2, 3, and 4 hours post Dose)]

   Serum concentrations for PAT-001 0.1% and PAT-001 0.2% looking at blood levels obtained at timepoints outlined

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients of either sex aged 12 years or older.

• Females of childbearing potential should use appropriate contraception. Women of childbearing potential must have a negative pregnancy test at screening and baseline visits.

• Patient and legal representative(s), if applicable, has provided written informed consent.

• Patient has congenital ichthyosis of either lamellar or X-Linked subtype.

• Patient has two contralateral comparable Treatment Areas (e.g., each arm is affected and treatments areas can be applied equally).

• Patient is, except for their ichthyosis, in good general health.

Exclusion Criteria:

• Patient is pregnant or breast feeding, or is planning to become pregnant during the study.

• Patient has inflammatory skin disease unrelated to ichthyosis.

• Patient is currently using concomitant retinoid therapy, within two weeks (topical) or 12 weeks (oral) of Visit 2/Baseline.

• Patient is currently taking concomitant immunosuppressive drugs, including systemic corticosteroids, within two weeks of Visit 2/Baseline.

• Patient is currently enrolled in an investigational drug or device study.

• Patient has used an investigational drug or investigational device treatment within 30 days prior to Visit 2/Baseline.

• Patient is unable to communicate or cooperate with the investigator due to language problems, impaired cerebral function, or physical limitations.

• Patient 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TCR Medical Corporation	San Diego	California	United States	92123
2	Yale Center for Clinical Investigation	New Haven	Connecticut	United States	06519
3	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	Paddington Testing Co., Inc	Philadelphia	Pennsylvania	United States	19103
5	Texas Dermatology and Laser Specialists	San Antonio	Texas	United States	78218

Sponsors and Collaborators

• Patagonia Pharmaceuticals, LLC

Investigators

• Study Director: Zachary Rome, BS, Sponsor GmbH

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 6, 2017

More Information

Publications

None provided.

• Responsible Party: Patagonia Pharmaceuticals, LLC
• ClinicalTrials.gov Identifier: NCT02864082
• Other Study ID Numbers: 205-9051-201
• First Posted: Aug 11, 2016
• Last Update Posted: Sep 29, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Patagonia Pharmaceuticals, LLC: X-linked, lamellar
• Additional relevant MeSH terms: Ichthyosis; Ichthyosis, Lamellar; Ichthyosiform Erythroderma, Congenital

Study Results

Participant Flow

Recruitment Details	Recruitment: March 8, 2017-February 13, 2018. Recruited at 5 clinics in United States associated with US Universities by practicing dermatologists
Pre-assignment Detail	Each patient received both vehicle application and either PAT-001 0.1% or PAT-001 0.2% on 2 different identical matching parts of their bodies (e.g, upper thighs). Since each of the 19 patients were treated with both PAT-001 and vehicle, the number of treatment areas was 38 (19 x 2) but the number of patients was 19.

Arm/Group Title	Group 1 PAT-001 0.1% and Vehicle	Group 2 PAT-001 0.2% and Vehicle
Arm/Group Description	Part 1 (8 weeks): Patients will have two comparable Treatment Areas on their bodies, for example both upper arms that have same degree of disease. PAT-001, 0.1% will be applied to one of those body parts for 8 weeks, applied twice a day. The matching body part will have vehicle applied twice a day for 8 weeks Part 2 (4 weeks): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.1% so that subjects cannot tell the difference between vehicle and PAT-001 based upon appearance.	Part 1 (8 weeks): Patients will have two comparable Treatment Areas on their bodies, for example both upper arms that have same degree of disease. PAT-001, 0.2% will be applied to one of those body parts for 8 weeks, applied twice a day. The matching body part will have vehicle applied twice a day for 8 weeks. Part 2 (4 weeks): Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001 0.1% so that subjects cannot tell the difference between vehicle and PAT-001 based upon appearance.
Period Title: Overall Study
STARTED	10	9
COMPLETED	7	5
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	Group 1 PAT-001 0.1% and Vehicle	Group 2 PAT-001 0.2% and Vehicle	Total
Arm/Group Description	Part 1 (weeks 0-8): Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1 (weeks 0-8): Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: (weeks 8-12) Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Total of all reporting groups
Overall Participants	10	9	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.5 (20.3)	47.2 (18.4)	42 (19.3)
Sex: Female, Male (Count of Participants)
Female	5 50%	4 44.4%	9 47.4%
Male	5 50%	5 55.6%	10 52.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	10 100%	9 100%	19 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%	9 100%	19 100%
BMI (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	28.8	26.4	27.7

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) in Part 1 of Trial (Weeks 0-8)
Description	The number of participants with AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported.
Time Frame	Day 0 through Day 57 (Weeks 0-8)

Outcome Measure Data

Analysis Population Description

Number of Participants with Adverse events

Arm/Group Title	Group 1 PAT-001 0.1%	Group 2 PAT-001 0.2%	Group 1 Vehicle	Group 2 Vehicle
Arm/Group Description	Part 1 (Weeks 0-8): Patients will have two comparable Treatment Areas of equal size and degree of severity: PAT-001, 0.1% will be applied to one of the 2 areas twice a day for 8 weeks Part 2 (Weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug.	Part 1 (Weeks 0-8): Patients will have two comparable Treatment Areas of equal size and degree of severity: PAT-001, 0.2% will be applied to one of the 2 areas twice a day for 8 weeks Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug.	Part 1 (Weeks 0-8): Patients will have two comparable Treatment Areas of equal size and degree of severity: Vehicle will be applied to one of the 2 areas twice a day for 8 weeks Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1 (Weeks 0-8): Patients will have two comparable Treatment Areas of equal size and degree of severity: Vehicle will be applied to one of the 2 areas twice a day for 8 weeks Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.
Measure Participants	10	9	10	9
Number of Subjects with TEAE	7 70%	7 77.8%	5 26.3%	5 NaN
Number of Treatment Emergent Adverse Events (TEAE) within treatment area	4 40%	5 55.6%	3 15.8%	3 NaN
Number of Deaths due to TEAE	0 0%	0 0%	0 0%	0 NaN
Number of Serious TEAE	0 0%	1 11.1%	0 0%	0 NaN
Number of Patients who Discontinued in the trial due to TEAE	1 10%	1 11.1%	0 0%	0 NaN
Number of Patients with Severe TEAE	1 10%	1 11.1%	0 0%	0 NaN
Number of Patients with Moderate TEAE	3 30%	3 33.3%	2 10.5%	2 NaN
Number of Patients with Mild TEAE	4 40%	6 66.7%	3 15.8%	3 NaN
Number of Patients Where the TEAE was Considered Definitely Related to Treatment	1 10%	1 11.1%	0 0%	0 NaN
Number of Patients where the TEAE was Considered Probably Related to Treatment	1 10%	0 0%	0 0%	0 NaN
Number of Patients Where the TEAE was Considered Possibly Related to Treatment	1 10%	4 44.4%	1 5.3%	1 NaN
Number of Patients Where the TEAE was Considered Not Related to Treatment	1 10%	5 55.6%	4 21.1%	4 NaN

2. Primary Outcome

Title	Incidence of Local Skin Reactions (LSRs) in Participants Treated With PAT-001 0.1%, 0.2% and/or Vehicle
Description	LSRs including burning/stinging, pain, and pruritus (itch) will be assessed in each Treatment Area using a four-point ordinal scale where 0=none, 1=mild, 2=moderate, and 3=severe (based on the investigator's evaluation of the skin reaction) at each clinic visit to allow a comparison between Treatment Groups and Test Articles. Only LSRs that require medical intervention (e.g., prescription medication) or require withholding or reduction in dosing frequency of the test articles will be documented in this LSR Table. Any LSRs that are not listed here will be recorded as AEs.
Time Frame	Up to Day 84 (Weeks 0-12)

Outcome Measure Data

Analysis Population Description

Participants may have had more than one type of LSR

Arm/Group Title	Group 1 PAT-001 0.1%	Group 1 Vehicle	Group 2 PAT-001 0.2%	Group 2 Vehicle
Arm/Group Description	Part 1 (weeks 0-8): Bilateral randomized comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% is applied to one side Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug.	Part 1 (weeks 0-8): Bilateral randomized comparison. Patients will have two comparable Treatment Areas: Vehicle, 0.0% will be applied to one of the sides Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1 (weeks 0-8): Bilateral randomized comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% will be applied to one side Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug.	Part 1 (weeks 0-8): Bilateral randomized comparison. Patients will have two comparable Treatment Areas: PAT-001 Vehicle, 0.0% will be applied to one side Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug.
Measure Participants	10	10	9	9
Application site pruritis (severe)	1 10%	0 0%	0 0%	0 NaN
Application site irritation (mild)	3 30%	2 22.2%	0 0%	0 NaN
Application site dermatitis (moderate)	0 0%	0 0%	1 5.3%	0 NaN
Application site rash (mild)	1 10%	0 0%	0 0%	1 NaN
Application site reaction (mild)	0 0%	0 0%	1 5.3%	0 NaN
Application site pain (moderate)	1 10%	0 0%	0 0%	0 NaN
Application site Pruritis (moderate)	1 10%	1 11.1%	0 0%	0 NaN
Application site Pruritis (mild)	1 10%	1 11.1%	0 0%	0 NaN
Application site Dermatitis (mild)	0 0%	0 0%	1 5.3%	2 NaN

3. Secondary Outcome

Title	Number of Participants Achieving Improvement to State of Clear, Almost Clear or Mild in the Investigator's Global Assessment (IGA) Using a Five-point Scale at Day 57 (Part 1)
Description	Overall severity of ichthyosis will be graded using a five-point scale Investigator Global Assessment (IGA) based upon a 5 point scale going from 0=clear., 1=almost clear, 2=mild, 3=moderate to 4=severe. Scoring is based upon investigator evaluation. This is a static morphological scale that refers to a point in time and not a comparison to Baseline.
Time Frame	Up to Day 57

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1 PAT-001 0.1%	Group 2 PAT-001 0.2%	Group 1 Vehicle	Group 2 Vehicle
Arm/Group Description	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.
Measure Participants	9	8	9	8
Count of Participants [Participants]	9 90%	8 88.9%	6 31.6%	7 NaN

4. Secondary Outcome

Title	Number of Participants Achieving an Improvement of at Least 1 Point Score in the Individual Clinical Signs/Symptoms of Erythema, Scaling, Fissuring and Papulation/Lichenification Using a Five-point Scale
Description	Overall severity of erythema (redness), scaling , fissuring (cracks in skin), and papulation/lichenification (skin thickening, increased pigmentation and/or exaggerated skin lines, formation of papules) will be graded using a five-point scale from 0=clear, 1=almost clear, 2=mild, 3=moderate to 4=severe. This is a static morphological scale that refers to a point in time and not a comparison to Baseline. This scoring is based upon investigator discretion.
Time Frame	Up to Day 57 (Weeks 0-8)

Outcome Measure Data

Analysis Population Description

IGA score improvement of at least 1 point on IGA for scaling, erythema, papulation/lichenification and fissuring at Day 57 in patients receiving continuous 0.1% and 0.2% PAT-001

Arm/Group Title	Group 1 PAT-001 0.1%	Group 2 PAT-001 0.2%	Group 1 Vehicle	Group 2 Vehicle
Arm/Group Description	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.
Measure Participants	9	8	9	8
Scaling	9 90%	6 66.7%	7 36.8%	8 NaN
Fissuring	6 60%	6 66.7%	5 26.3%	6 NaN
Papulation/lichenification	9 90%	6 66.7%	6 31.6%	7 NaN
Erythema	5 50%	5 55.6%	4 21.1%	6 NaN

5. Other Pre-specified Outcome

Title	Pharmacokinetics of PAT-001 0.1% and 0.2% at Different Timepoints
Description	Serum concentrations for PAT-001 0.1% and PAT-001 0.2% looking at blood levels obtained at timepoints outlined
Time Frame	Day 1 (0,1, 2, 3, and 4 hours post Dose)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2 (Part 1)
Arm/Group Description	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.1% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.	Part 1: Bilateral comparison. Patients will have two comparable Treatment Areas: PAT-001, 0.2% (e.g., left side) and Vehicle, 0.0% (e.g., right side). Part 2: Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001.
Measure Participants	2	3
Pre-Dose	1.495 (0.6718)	2.48 (1.795)
1 Hour	1.5 (0.6505)	2.227 (1.3725)
2 Hours	1.425 (0.5303)	2.12 (1.2257)
3 Hours	1.37 (0.297)	2.063 (1.5332)
4 Hours	1.375 (0.0778)	1.453 (0.3625)

Adverse Events

Time Frame	84 Days
Arm/Group Title	Group 1 PAT-001 0.1%		Group 2 PAT-001 0.2%		Group 1 Vehicle		Group 2 Vehicle
Arm/Group Description	Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: PAT-001, 0.1% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug.		Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: PAT-001, 0.2% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug.		Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: Vehicle, 0.0% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.1% to both Treatment Areas. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. PAT-001, 0.1%: PAT-001 is a topical ointment. PAT-001, 0.1% contains 0.1% of active drug.		Part 1 (weeks 0-8) Patients will have two comparable identical Treatment Areas: Vehicle 0.0% will be applied to one of these areas. Part 2 (weeks 8-12): Patients will apply PAT-001, 0.2% to both Treatment Areas. Vehicle: Vehicle topical ointment contains 0.0% of active drug and is color matched to the active test article, PAT-001. PAT-001, 0.2%: PAT-001 is a topical ointment. PAT-001, 0.2% contains 0.2% of active drug.
All Cause Mortality
	Group 1 PAT-001 0.1%		Group 2 PAT-001 0.2%		Group 1 Vehicle		Group 2 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)		0/10 (0%)		0/9 (0%)
Serious Adverse Events
	Group 1 PAT-001 0.1%		Group 2 PAT-001 0.2%		Group 1 Vehicle		Group 2 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		1/9 (11.1%)		0/10 (0%)		0/9 (0%)
Infections and infestations
C. difficile colitis	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Novavirus gastroenteritis	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Psychiatric disorders
mental status changes	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1 PAT-001 0.1%		Group 2 PAT-001 0.2%		Group 1 Vehicle		Group 2 Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/10 (70%)		7/9 (77.8%)		2/10 (20%)		1/9 (11.1%)
General disorders
Application site pruritis	3/10 (30%)	6	0/9 (0%)	0	2/10 (20%)	2	1/9 (11.1%)	1
Application site pain	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Infections and infestations
C. difficile colitis	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Application site folliculitis	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Gastroenteritis novovirus	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Tooth infection	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Upper Respiratory Tract Infection	0/10 (0%)	0	2/9 (22.2%)	2	0/10 (0%)	0	0/9 (0%)	0
Urinary Tract Infection	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	2/10 (20%)	2	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Contusion	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Procedural dizziness	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Investigations
Blood triglycerides increased	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Transaminases increased	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	1/10 (10%)	1	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Psychiatric disorders
Mental status changes	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Application site dermatitis	2/10 (20%)	2	0/9 (0%)	0	0/10 (0%)	0	0/9 (0%)	0
Dermatitis contact	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0
Skin lesion	0/10 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/9 (0%)	0

Limitations/Caveats

Data should be interpreted with caution due to small sample sizes

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.