Atopic Dermatitis
Conditions
Brief summary
A Randomised, Adaptive Design, Double-Blind (3rd Party Open), Placebo Controlled, Sequential Group Study to Determine the Safety,Tolerability, Pharmacokinetics and Efficacy of Twice Daily Application of a Topical ZPL-5212372 (1.0% w/w) Ointment Administered for up to 2 Weeks in Adult Healthy Volunteers and Patients with Moderate to Severe Atopic Dermatitis
Detailed description
This study was a randomised, adaptive design, double blind (3rd party open), placebo controlled, sequential group study in both healthy volunteers and patients with moderate to severe AD. This study was divided into 3 separate, sequential cohorts: * Cohort 1 were to assess safety, toleration and pharmacokinetics (PK) with intensive monitoring as in-patients over 7 days of dosing in healthy volunteers. * Cohort 2 were to assess safety, toleration and PK with intensive monitoring as in-patients over 7 days of dosing in moderate to severe AD patients. * Cohort 3 were to assess efficacy, safety, toleration and PK as out-patients over 14 days of dosing in moderate to severe AD patients. Subjects received 1.0% (w/w) ZPL-5212372 or matched placebo ointment topically, twice daily.
Interventions
DRUGZPL-5212372 1% w/w Ointment BID
DRUGPlacebo Ointment BID
Sponsors
Ziarco Pharma Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males or females, aged between 18 and 55 years, inclusive (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests). or Males and females aged 18-65 years inclusive with physician documented history or diagnosis of atopic dermatitis for at least 6 months prior to screening. AD should be diagnosed by the Eichenfield revised criteria of Hanifin and Rajka. For Atopic Dermatitis Patients: Eczema Area and Severity Index (EASI) of ≥9 and \<48 at Screening and an EASI of ≥12 and \<48 at Day 1. An Investigator's Global Assessment (IGA) score ≥ 3 at both Screening and Day 1. Atopic dermatitis affecting between ≥10 to \<40% BSA at Screening and ≥10% to \<50% BSA on Day 1. All Subjects: Evidence of a personally signed and dated informed consent form, indicating that the subject has been informed of all pertinent aspects of the study.
Exclusion criteria
For Healthy Subjects * Evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * Have tattoos covering areas of skin to be dosed with study ointment. * Subjects who are hirsute in areas of skin to be dosed with study ointment. * Subjects who have received treatment with an investigational drug within 3 months prior to screening. For Atopic Dermatitis Patients: * AD of such severity (EASI \>48) that the subject could not comply with the demands of the study and/or the subject is not a suitable candidate for a placebo-controlled study. * Have concomitant skin disease or infection (e.g. acne, impetigo) or presence of skin comorbidities in the study area to be dosed that may interfere with study assessments. * Have received phototherapy (e.g. UVA, UVB or PUVA therapy), or systemic therapy (e.g. immunosuppressants \[such as cyclosporine, azathioprine, methotrexate\], cytostatics) known or suspected to have an effect on AD, within 4 weeks of the start of the study. All other biologics should not have been used within 3 months of the start of study. * Have received systemic corticosteroids (e.g. oral, intravenous, intraarticular, rectal) within 4 weeks of the start of the study. Subjects on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal CS may participate. * Patients treated with oral antihistamines or topical calcineurin inhibitors or topical steroids within 7 days of starting study; intranasal antihistamines for the treatment of allergic rhinitis are acceptable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Days 1, 5, 8, 10, and 15 | The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease. |
| Percent Change From Baseline in EASI Score in Cohort 3 | Day 1 and Day 14 | The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders on Investigators Global Assessment in Cohort 3 | Day 14 | The following secondary endpoints were assessed for IGA: A subject was considered as having IGA success if they achieved a score of 'Clear' or 'Almost clear'; note, as subjects required a score of ≥3 to enter the study they must have had a reduction of ≥2 from baseline to achieve success A subject was considered as having an IGA response if they achieved a score of 'Clear' or 'Almost clear', or a reduction of ≥2 from baseline IGA was summarized for the FAS with counts and percentages by treatment at each visit. |
| Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3 | Day 1 to day 14 | Numerical Rating Scale (NRS) for Pruritus (worst itch). The Pruritus NRS is an assessment tool that will be used to assess the subject's worst itch as a result of AD in the previous 24 hours. They will be asked the following question: On a scale of 0 (No Itching) to 10 (Itching as bad as you can imagine), please rate the WORST itching that you felt over the last 24 hours. |
| Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | Day 14 | The proportion of subjects who achieved EASI-50 and EASI-75 responses at Week 2 were compared between treatment groups. EASI-50 was defined as a ≥50% reduction from baseline in EASI score at Week 2. EASI-75 was defined as a ≥75% reduction from baseline in EASI score at Week 2. |
| Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | End of treatment (day 15) | Patient Global Impression of Change (PGIC) The PGIC scores were summarised for the FAS with counts and percentages in each treatment group. All data collected were included. The PGIC was dichotomized into responders, defined as responses of 'Very Much Improved', 'Much Improved' or 'Minimally improved' and non-responders (all other responses plus missing data). |
| Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3 | Day 1 to day 14 | Body Surface Area (BSA). The percentage BSA affected was summarised at each visit, including change from baseline, by treatment group, using the Full Analysis Set. |
Other
| Measure | Time frame | Description |
|---|---|---|
| ZPL-5212372 AUCt for Patients in Cohort 2 | Day 1, Day 7 | PK parameters for patients who had ointment applied over 40% BSA. |
| ZPL-5212372 Cmax for Patients in Cohort 2 | Day 1, Day 7 | PK parameters for patients who had ointment applied over 40% BSA. |
| ZPL-5212372 Trough Plasma Concentrations in Cohort 3 | Day 5, Day 8, Day 10, Day 15 | PK parameters for patients who had ointment applied over 40% BSA. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 (ZPL-5212372) ZPL-5212372 1% w/w Ointment BID | 8 |
| Cohort 1 - Placebo Placebo Ointment BID | 4 |
| Cohort 2 (ZPL-5212372) ZPL-5212372 1% w/w Ointment BID | 8 |
| Cohort 2b - Placebo Placebo Ointment BID | 3 |
| Cohort 3 (ZPL-5212372) ZPL-5212372 1% w/w OIntment BID | 20 |
| Cohort 3 - Placebo Placebo Ointment BID | 10 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Cohort 1 (ZPL-5212372) | Cohort 1 - Placebo | Cohort 2 (ZPL-5212372) | Cohort 2b - Placebo | Cohort 3 (ZPL-5212372) | Cohort 3 - Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 25.4 years STANDARD_DEVIATION 21 | 25.8 years STANDARD_DEVIATION 22.5 | 22.3 years STANDARD_DEVIATION 4.86 | 32.9 years STANDARD_DEVIATION 12.77 | 27.6 years STANDARD_DEVIATION 8.41 | 29.2 years STANDARD_DEVIATION 5.77 | 26.3 years STANDARD_DEVIATION 8.4 |
| Race and Ethnicity Not Collected | — | — | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 12 Participants | 4 Participants | 24 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 7 Participants | 0 Participants | 8 Participants | 6 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 6 | 0 / 1 | 0 / 3 | 0 / 2 | 0 / 6 | 0 / 1 | 0 / 2 | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 2 / 2 | 3 / 6 | 1 / 1 | 1 / 3 | 2 / 2 | 4 / 6 | 1 / 1 | 2 / 2 | 17 / 20 | 9 / 10 |
| serious Total, serious adverse events | 0 / 2 | 0 / 6 | 0 / 1 | 0 / 3 | 0 / 2 | 0 / 6 | 0 / 1 | 0 / 2 | 0 / 20 | 0 / 10 |
Outcome results
Primary
Percent Change From Baseline in EASI Score in Cohort 3
The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease.
Time frame: Day 1 and Day 14
Population: Full Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score in Cohort 3 | Observed case | -34.24 percent change from baseline in EASI | Standard Error 6.288 |
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score in Cohort 3 | Multiple imputations | -34.04 percent change from baseline in EASI | Standard Error 6.445 |
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score in Cohort 3 | Last observation carried forward | -34.04 percent change from baseline in EASI | Standard Error 7.564 |
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score in Cohort 3 | Worst case imputation | -33.94 percent change from baseline in EASI | Standard Error 10.794 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score in Cohort 3 | Worst case imputation | 3.66 percent change from baseline in EASI | Standard Error 15.286 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score in Cohort 3 | Observed case | -34.29 percent change from baseline in EASI | Standard Error 10.68 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score in Cohort 3 | Last observation carried forward | -15.77 percent change from baseline in EASI | Standard Error 10.712 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score in Cohort 3 | Multiple imputations | -31.03 percent change from baseline in EASI | Standard Error 11.207 |
Comparison: Observed casep-value: 0.501690% CI: [-21.24, 21.34]ANCOVA
Comparison: Multiple imputationsp-value: 0.408290% CI: [-24.39, 18.36]ANCOVA
Comparison: Last observation carried forwardp-value: 0.087890% CI: [-40.65, 4.11]ANCOVA
Comparison: Worst case imputationp-value: 0.027590% CI: [-69.53, -5.66]ANCOVA
Primary
Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case
The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease.
Time frame: Days 1, 5, 8, 10, and 15
Population: Full Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 5 | -16.68 percent change from baseline in EASI | Standard Error 5.823 |
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 10 | -32.50 percent change from baseline in EASI | Standard Error 5.339 |
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 15 | -34.24 percent change from baseline in EASI | Standard Error 6.228 |
| Cohort 3 (ZPL-5212372) | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 8 | -27.36 percent change from baseline in EASI | Standard Error 5.284 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 15 | -34.49 percent change from baseline in EASI | Standard Error 8.445 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 5 | -4.96 percent change from baseline in EASI | Standard Error 8.247 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 8 | -21.41 percent change from baseline in EASI | Standard Error 8.358 |
| Cohort 3 - Placebo | Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case | Day 10 | -26.49 percent change from baseline in EASI | Standard Error 8.445 |
Comparison: Day 5p-value: 0.128490% CI: [-28.85, 5.51]ANCOVA
Comparison: Day 8p-value: 0.276590% CI: [-22.85, 10.95]ANCOVA
Comparison: Day 10p-value: 0.276590% CI: [-23.08, 11.06]ANCOVA
Comparison: Day 15p-value: 0.501690% CI: [-21.24, 21.34]ANCOVA
Secondary
Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3
Body Surface Area (BSA). The percentage BSA affected was summarised at each visit, including change from baseline, by treatment group, using the Full Analysis Set.
Time frame: Day 1 to day 14
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 (ZPL-5212372) | Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3 | -6.26 score on a scale | Standard Error 2.588 |
| Cohort 3 - Placebo | Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3 | -3.61 score on a scale | Standard Error 4.075 |
p-value: 0.281290% CI: [-10.4, 5.09]Shapiro-Wilkes test
Secondary
Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3
Numerical Rating Scale (NRS) for Pruritus (worst itch). The Pruritus NRS is an assessment tool that will be used to assess the subject's worst itch as a result of AD in the previous 24 hours. They will be asked the following question: On a scale of 0 (No Itching) to 10 (Itching as bad as you can imagine), please rate the WORST itching that you felt over the last 24 hours.
Time frame: Day 1 to day 14
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 3 (ZPL-5212372) | Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3 | -2.46 score on a scale | Standard Error 0.692 |
| Cohort 3 - Placebo | Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3 | -2.54 score on a scale | Standard Error 1.075 |
p-value: 0.523390% CI: [-2.02, 2.16]Shapiro-Wilkes test
Secondary
Percentage of Responders on Investigators Global Assessment in Cohort 3
The following secondary endpoints were assessed for IGA: A subject was considered as having IGA success if they achieved a score of 'Clear' or 'Almost clear'; note, as subjects required a score of ≥3 to enter the study they must have had a reduction of ≥2 from baseline to achieve success A subject was considered as having an IGA response if they achieved a score of 'Clear' or 'Almost clear', or a reduction of ≥2 from baseline IGA was summarized for the FAS with counts and percentages by treatment at each visit.
Time frame: Day 14
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 3 (ZPL-5212372) | Percentage of Responders on Investigators Global Assessment in Cohort 3 | 5.0 Percentage of responders |
| Cohort 3 - Placebo | Percentage of Responders on Investigators Global Assessment in Cohort 3 | 10.0 Percentage of responders |
p-value: 0.595% CI: [0.01, 19.2]Shapiro-Wilkes test
Secondary
Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3
The proportion of subjects who achieved EASI-50 and EASI-75 responses at Week 2 were compared between treatment groups. EASI-50 was defined as a ≥50% reduction from baseline in EASI score at Week 2. EASI-75 was defined as a ≥75% reduction from baseline in EASI score at Week 2.
Time frame: Day 14
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 3 (ZPL-5212372) | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-50 responder | 7 participants |
| Cohort 3 (ZPL-5212372) | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-50 Non-responder | 13 participants |
| Cohort 3 (ZPL-5212372) | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-75 responder | 3 participants |
| Cohort 3 (ZPL-5212372) | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-75 Non-responder | 17 participants |
| Cohort 3 - Placebo | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-75 Non-responder | 10 participants |
| Cohort 3 - Placebo | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-50 responder | 3 participants |
| Cohort 3 - Placebo | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-75 responder | 0 participants |
| Cohort 3 - Placebo | Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3 | EASI-50 Non-responder | 7 participants |
Comparison: EASI 50p-value: 0.478990% CI: [0.28, 10.75]ANCOVA
Comparison: EASI-75p-value: 0.390% CI: [0.24, 999]ANCOVA
Secondary
Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3
Patient Global Impression of Change (PGIC) The PGIC scores were summarised for the FAS with counts and percentages in each treatment group. All data collected were included. The PGIC was dichotomized into responders, defined as responses of 'Very Much Improved', 'Much Improved' or 'Minimally improved' and non-responders (all other responses plus missing data).
Time frame: End of treatment (day 15)
Population: Full analysis set
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Very much improved | 4 Participants |
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Much improved | 5 Participants |
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Minimally improved | 7 Participants |
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | No change | 3 Participants |
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Minimally worse | 1 Participants |
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Much worse | 0 Participants |
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Very much worse | 0 Participants |
| Cohort 3 (ZPL-5212372) | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Missing | 0 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Missing | 0 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Very much improved | 1 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Minimally worse | 1 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Much improved | 1 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Very much worse | 0 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Minimally improved | 4 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | Much worse | 2 Participants |
| Cohort 3 - Placebo | Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3 | No change | 1 Participants |
p-value: 0.245595% CI: [0.45, 13.26]t-test, 1 sided
Other Pre-specified
ZPL-5212372 AUCt for Patients in Cohort 2
PK parameters for patients who had ointment applied over 40% BSA.
Time frame: Day 1, Day 7
Population: Pharmacokinetic analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 3 (ZPL-5212372) | ZPL-5212372 AUCt for Patients in Cohort 2 | 1301 h*pg/mL |
| Cohort 3 - Placebo | ZPL-5212372 AUCt for Patients in Cohort 2 | 1249 h*pg/mL |
Other Pre-specified
ZPL-5212372 Cmax for Patients in Cohort 2
PK parameters for patients who had ointment applied over 40% BSA.
Time frame: Day 1, Day 7
Population: Pharmacokinetic analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 3 (ZPL-5212372) | ZPL-5212372 Cmax for Patients in Cohort 2 | 300.6 pg/mL |
| Cohort 3 - Placebo | ZPL-5212372 Cmax for Patients in Cohort 2 | 135.3 pg/mL |
Other Pre-specified
ZPL-5212372 Trough Plasma Concentrations in Cohort 3
PK parameters for patients who had ointment applied over 40% BSA.
Time frame: Day 5, Day 8, Day 10, Day 15
Population: Pharmacokinetic analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 3 (ZPL-5212372) | ZPL-5212372 Trough Plasma Concentrations in Cohort 3 | 88.985 pg/mL |
| Cohort 3 - Placebo | ZPL-5212372 Trough Plasma Concentrations in Cohort 3 | 114.700 pg/mL |
| Day 10 | ZPL-5212372 Trough Plasma Concentrations in Cohort 3 | 113.920 pg/mL |
| Day 15 | ZPL-5212372 Trough Plasma Concentrations in Cohort 3 | 90.825 pg/mL |