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This was a randomized, double blind, placebo controlled, parallel group study in approximately 90 subjects with moderate-severe AD Eczema Area and Severity Index (EASI) ≥12 and ≤ 48 (0-72 scale). Following a run-in subjects were randomized to receive either oral 30 mg ZPL-3893787 once daily (od) or placebo od for 8 weeks (56 days).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ZPL-3893787 | Experimental | 30 mg ZPL-3893787 orally once daily for 8 weeks. |
|
| Placebo | Placebo Comparator | 1 capsule orally once daily for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZPL-3893787 | Drug | ZPL-3893787 |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | The participant used the Pruritus NRS to rate his or her worst itch in the previous 12 hours. This was assessed twice daily (in the morning soon after rising and the evening prior to retiring) and recorded in the eDiary. The scale ranges from 0 (no itching) to 10 (itching as bad as can be imagined). If only 1 measurement was collected on a particular day, that score was counted as the worst measurement. | Baseline to Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Eczema Area and Severity Index (EASI) Score | The EASI is a validated tool used to measure the severity and extent of atopic eczema over 4 body regions (head and neck, upper limbs, trunk, and lower limbs). The intensity of a representative area of eczema and the approximate percentage affected by eczema are calculated for each region. A representative area of eczema is selected for each body region. The intensity of redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) of eczema is assessed as: 0 - None
Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions |
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Inclusion Criteria:
Males and females aged 18-65 years inclusive with physician documented history or diagnosis of atopic dermatitis for at least 12 months prior to screening. Chronic AD should be diagnosed by the Eichenfield revised criteria of Hanifin and Rajka (Eichenfield, 2004)
Eczema Area and Severity Index (EASI) of ≥12 and <48.
An Investigator's Global Assessment (IGA) score ≥ 3 at both Screening and Day 0.
A mean pruritus score of ≥ 5 on a 0-10 scale over the 7 day Run In (Days -7 to -1)
Atopic dermatitis affecting ≥10% BSA
Exclusion Criteria:
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 concurrent skin disease (e.g. acne) of such severity in the study area that it could interfere with the study evaluation or presence of skin comorbidities that may interfere with study assessments.
Have an active skin infection or any other clinically apparent infections.
Hypersensitivity to mometasone or to any other ingredients contained by the topical corticosteroid product used as rescue medication in the study.
Have received phototherapy (e.g. UVA, UVB), or systemic therapy (e.g. immunosuppressants, cytostatics) known or suspected to have an effect on AD, within 4 weeks of the start of the Run In.
Have received systemic corticosteroids ([CS] e.g. oral, intravenous, intraarticular, rectal) within 4 weeks of the start of the Run in. Subjects on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal CS may participate.
Were treated with oral antihistamines or topical calcineurin inhibitors or topical steroids within 7 days of starting Run In; intranasal antihistamines for the treatment of allergic rhinitis are acceptable.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Belgium Study Site | Brussels | Belgium | ||||
| Belgium Study Site |
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The first informed consent was on 18 May 2015. Subjects were randomly assigned 2:1 to receive either 30 mg ZPL-3893787 or matching placebo. The randomization was stratified by baseline worst daily pruritus NRS score (≤ 7.5 and > 7.5) determined from the mean pruritus score (worst itch over 24 hours) collected during the 7-day Run-in Period.
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| ID | Title | Description |
|---|---|---|
| FG000 | ZPL-3893787 | 30 mg ZPL-3893787 orally once daily for 8 weeks. |
| FG001 | Placebo | 1 capsule orally once daily for 8 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Drug |
Matched Placebo |
|
| Baseline to Week 8 |
| Leuven |
| Belgium |
| Belgium Study Site | Liège | Belgium |
| German Study Site | Goch | Germany |
| German Study Site | Hamburg | Germany |
| German Study Site | Hanover | Germany |
| German Study Site | Mainz | Germany |
| German Study Site | Münster | Germany |
| Polish Study Site | Bialystok | Poland |
| Polish Study Site | Gdansk | Poland |
| Polish Study Site | Lodz | Poland |
| Polish Study Site | Poznan | Poland |
| Polish Study Site | Tarnów | Poland |
| UK Study Centre | Blackpool | United Kingdom |
| UK Study Centre | Cannock | United Kingdom |
| UK Study Centre | Leeds | United Kingdom |
| UK Study Centre | Manchester | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
|
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Full Analysis Set (FAS): Included all randomized subjects who received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | ZPL-3893787 | 30 mg ZPL-3893787 orally once daily for 8 weeks. |
| BG001 | Placebo | 1 capsule orally once daily for 8 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Fitzpatrick Skin Type | The Fitzpatrick scale is a numerical classification schema for human skin color. The scale ranges from I to VI and is defined as: Type I - always burns, never tans (palest; freckles). Type II - usually burns, tans minimally Type III - sometimes mild burn, tans uniformly Type IV - burns minimally, always tans well (moderate brown) Type V - very rarely burns, tans very easily (dark brown) Type VI - never burns (deeply pigmented dark brown to darkest brown) | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) | The participant used the Pruritus NRS to rate his or her worst itch in the previous 12 hours. This was assessed twice daily (in the morning soon after rising and the evening prior to retiring) and recorded in the eDiary. The scale ranges from 0 (no itching) to 10 (itching as bad as can be imagined). If only 1 measurement was collected on a particular day, that score was counted as the worst measurement. | Full Analysis Set (FAS): Included all randomized subjects who received at least 1 dose of study drug. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 8 |
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| Secondary | Change From Baseline in Eczema Area and Severity Index (EASI) Score | The EASI is a validated tool used to measure the severity and extent of atopic eczema over 4 body regions (head and neck, upper limbs, trunk, and lower limbs). The intensity of a representative area of eczema and the approximate percentage affected by eczema are calculated for each region. A representative area of eczema is selected for each body region. The intensity of redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) of eczema is assessed as: 0 - None
Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions | FAS: All randomized subjects who received at least one dose of study treatment. | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 8 |
|
|
Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ZPL-3893787 | 30 mg ZPL-3893787 orally once daily for 8 weeks. | 0 | 65 | 0 | 65 | 15 | 65 |
| EG001 | Placebo | 1 capsule orally once daily for 8 weeks. | 0 | 33 | 1 | 33 | 10 | 33 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ulcerative keratitis (ulcus corneae left eye) | Eye disorders | MedDRA (18.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Sinus arrhythmia | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
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| Pain | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Thirst | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Drug ineffective | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Fatigue | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Decreased activity | General disorders | MedDRA (18.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
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| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
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The terms and conditions of the agreements with investigators may vary. However, the investigator is not prohibited from publishing. Any publications from a single site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| Male |
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| Type II |
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| Type III |
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| Type IV |
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| Type V |
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| Type VI |
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| Change from Baseline |
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| Participants |
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