Atopic Dermatitis MedDRA version: 18.1 Level: LLT Classification code 10003639 Term: Atopic dermatitis System Organ Class: 100000004858
Conditions
Interventions
Product Name: ZPL-5212372
Pharmaceutical Form: Ointment
INN or Proposed INN: ZPL-5212372
Current Sponsor code: ZPL-5212372
Concentration
Sponsors
Ziarco Pharma Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: COHORT 1 1 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). 2 Females should be either of non-child-bearing potential or must agree to use highly effective methods of contraception. Males with partners who are WOCBP must also use contraception 3 Body weight of = 50 kg. 4 Body Mass Index of =34.9 kg/m^2. 5 Subjects must have a Fitzpatrick Skin Type of between I to III to be included in the study. 6 Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. 7 Evidence of a personally signed and dated informed consent form, indicating that the subject has been informed of all pertinent aspects of the study. COHORTS 2 AND 3 1 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. 2 Females should be either of non-child-bearing potential or must agree to use highly effective methods of contraception. Males with partners who are WOCBP must also use contraception 3 Body weight of = 50 kg. 4 Body Mass Index of =34.9 kg/m^2. 5 Eczema Area and Severity Index (EASI) of =9 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: COHORT 1 1 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). 2 Have tattoos covering areas of skin to be dosed. 3 Subjects who are hirsute in areas of skin to be dosed. 4 Subjects who are unwilling to stop hair removal by any means to skin areas to be dosed for 2 weeks prior to randomisation and throughout the duration of the study. 5 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. 6 Hypersensitivity to any excipients in the study ointment formulation, study emollient or study shower cream. 7 Hypersensitivity to any laundry detergents. 8 Use of a tanning booth/parlour/sunbathing (including excessive exposure to sunlight) or use of tanning products within 4 weeks before start of the study and for the duration of their participation in the study. 9 History of sensitivity to NSAIDs. 10 Clinically significant cardiac disease or ECG abnormalities. The PI should decide whether ECG abnormalities other than those listed are clinically significant and should exclude the subject from enrolment. COHORTS 2 AND 3 1 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. 2 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. 3 Patients who are hirsute in areas of skin to be dosed. 4 Patients who are unwilling to stop hair removal by any means to skin areas to be dosed for 2 weeks prior to randomisation and throughout the duration of the study. 5 Hypersensitivity to any excipients in the study ointment formulation, study emollient or study shower cream. 6 Hypersensitivity to any laundry detergents (Cohort 2 only). 7 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. 8 Have received systemic corticosteroids 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. 9 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. 10 Use of a tanning booth/parlour/sunbathing or use of tanning products within 4 weeks before start of the study and for the duration of their participation in the study. 11 Have used antiseptic treatments (e.g. bleach baths, potassium permanganate etc.) with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: COHORT 1 Primary Endpoints: Safety Adverse events - Continuous Local tolerance assessments - Day 1-9 Supine vital signs (BP and pulse rate) - screening and at least daily on Day 1-9 and follow up 12-lead ECG - screening and at least daily on Day 1-9 and follow up Laboratory safety tests (clinical chemistry, haematology and urinalysis) - screening and at least daily on Day 1-6, Day 9 and follow up COHORT 2 Primary Endpoints: Safety Adverse events, supine vital signs (BP and pulse rate), 12-lead ECG, laboratory safety tests (clinical chemistry, haematology and urinalysis) - all as cohort 1 COHORT 3 Primary Endpoints: Efficacy Percentage change from baseline in the Eczema Area and Severity Index (EASI) score - screening Days 1, 5, 8, 10, 15 and at follow up ; Main Objective: Cohorts 1 and 2 To assess the safety and tolerability, local and systemic, of ZPL-5212372 administered as a topical ointment (containing 1.0% (w/w) concentration of ZPL-5212372) twice daily, for 1 week, to healthy subjects and patients with moderate to severe AD. Cohort 3 To evaluate the efficacy of ZPL-5212372 administered as a topical ointment (containing 1.0% (w/w) concentration of ZPL-5212372) twice daily, for 2 weeks, to patients with moderate to severe AD. ; Secondary Objective: Cohorts 1 and 2 To investigate the systemic pharmacokinetics of ZPL-5212372 following single and multiple dose topical applications of a 1.0% (w/w) concentration of ZPL-5212372 ointment, administered twice daily, for 1 week, to healthy subjects and patients with moderate to severe AD. Cohort 3 To assess the safety a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): COHORT 1 ZPL-5212372 plasma concentrations Day 1 (sd): AUCt, Cmax and Tmax ZPL-5212372 plasma concentrations Day 7 (ss): AUClast, AUCt, Cmax, Tmax, and t½. Observed accumulation ratios based on AUCt and Cmax COHORT 2 ZPL-5212372 plasma concentrations Day 1 (sd): AUCt, Cmax and Tmax ZPL-5212372 plasma concentrations Day 7 (ss): AUClast, AUCt, Cmax, Tmax, and t½. Observed accumulation ratios based on AUCt and Cmax COHORT 3 Secondary Endpoints: Efficacy Change from baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) over 24 hours Change from baseline in the NRS for Sleep Disturbance Change from baseline in Duration of Itching Change from baseline in Verbal Rating Score (VRS) for Pruritus Change from baseline in BSA Reduction in Investigators Global Assessment (IGA) Score (subject will be deemed to have had a response with a reduction from baseline of at least 2 points) Patient Global Impression of Change (PGIC) Secondary Endpoints: Safety Adverse events, supine vital signs (BP and pulse rate), 12-lead ECG, laboratory safety tests (clinical chemistry, haematology and urinalysis). Secondary Endpoints: Pharmacokinetics Trough Plasma ZPL-5212372 concentrations ; Timepoint(s) of evaluation of this end point: COHORT 1 Plasma concentrations on Days 1 and 7 COHORT 2 Plasma concentrations on Days 1 and 7 COHORT 3 Change from baseline in: Numerical Rating Score (NRS) for Pruritus (Worst Itch) over 24 hours, NRS for Sleep Disturbance, Duration of Itching, Verbal Rating Score (VRS) f | — |
Countries
United Kingdom
Contacts
Public ContactLynn Purkins
Ziarco Pharma Ltd
Outcome results
None listed