Dermatitis, Atopic
Conditions
Keywords
EPAAC, Atopic children, Asthma, XYZAL, Levocetirizine
Brief summary
The Early Prevention of Asthma in Atopic Children (EPAAC™). 24 months study to evaluate the efficacy and safety of levocetirizine (LCTZ) in preventing the onset of asthma in 12 to 24 months old children.
Interventions
DRUGPlacebo
Pharmaceutical form: Oral drops Route of administration: Oral use
DRUGLevocetirizine
Pharmaceutical form: Oral drops Concentration: 5 mg/ml Route of administration: Oral use
Sponsors
UCB Pharma SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Months to 24 Months
Healthy volunteers
No
Inclusion criteria
Inclusion criteria which must be verified during screening visit (V1): * Children of either sex aged between 12 and 24 months * Subjects suffering from symptoms of Atopic Dermatitis (AD) lasting cumulatively for at least 2 months since birth * Modified Severity Scoring of Atopic Dermatitis (SCORAD) Index \>= 10 * Subjects whose biological mother or father, or one sibling has a well-documented history of atopy (AD, allergic rhinitis or asthma) Inclusion criteria which must be verified during randomization (V2): * Results of the Radio-allergosorbant (RAST) test for grass pollen (GP) and house dust mite (HDM) are available and Immunoglobulin E (IgE) level against GP \>= 0.35 kUA/l and/or IgE level against HDM ≥ 0.35 kUA/l * Safety laboratory results are within the normal range of the central laboratory or considered as not clinically significant or study disease related by the Investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Asthma During the Treatment Period | During the treatment period (18 months) | The time to onset of asthma was defined as the period elapsed between the randomization visit (V2) and the date of onset of asthma. Instead of the median the first Quartile is reported since the median (50%) was not reached. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Days With Symptoms of Wheezing | During the treatment period (18 months) | The caring person was to note on the diary card each each wheezing event occurring at any time. |
| Percentage of Days With Symptoms of Nocturnal Cough | During the treatment period (18 months) | The caring person was to note on the diary card each nocturnal cough event with sleep disturbances occurring from 7:00 pm to 7:00 am |
| Percentage of Subjects Using Asthma Medication | During the treatment period (18 months) | The following asthma medications were taken into consideration: Beta 2-mimetics, cromoglycates, inhaled corticoids, systemic corticoids, leukotriene antagonists |
| Percentage of Days of Use of Asthma Medication | During the treatment period (18 months) | The following asthma medications were taken into consideration: Beta 2-mimetics, cromoglycates, inhaled corticoids, systemic corticoids, leukotriene antagonists |
| Percentage of Days With Symptoms of Either Wheezing or Nocturnal Cough | During the treatment period (18 months) | The caring person was to note on the diary card each nocturnal cough event with sleep disturbances occurring from 7:00 pm to 7:00 am and each wheezing event occurring at any time together with the treatment for these symptoms. |
| Percentage of Days of Use of Medication for Atopic Dermatitis | During the treatment period (18 months) | The following medications for Atopic Dermatitis were taken into consideration: Emollients, local antihistamines; Local steroids class (LSC) A, non-steroidal anti-inflammatory (NSAI) creams, tar; Local steroids class B; Local steroids class C; Local antibiotics or antiseptics; Oral H1 anti-histamines (a-h); Local antibiotics (ABs) or antiseptics |
| Percentage of Subjects With Urticaria | During the treatment period (18 months) | Urticaria was defined as typical hives or areas of skin swelling, redness and itching distinctly different from the child's usual inflamed skin lesions of Atopic Dermatitis (AD), associated with an infection or food allergen ingestion/contact or other trigger. |
| Number of Episodes of Urticaria Per Subject | During the treatment period (18 months) | Urticaria was defined as typical hives or areas of skin swelling, redness and itching distinctly different from the child's usual inflamed skin lesions of Atopic Dermatitis (AD), associated with an infection or food allergen ingestion/contact or other trigger. |
| Percentage of Subjects Using Medication for Atopic Dermatitis | During the treatment period (18 months) | The following medications for Atopic Dermatitis were taken into consideration: Topical corticosteroids/ Local Steroids Class A, non-steroidal anti-inflammatory (NSAI) creams, tar/ Local Steroids Class B/ Local Steroids Class C/ Topical tacrolimus/ Topical pimecrolimus/ Systemic H1 anti-histamines/ Local antibiotics or antiseptics |
Participant flow
Recruitment details
The study started to enroll patients in March 2002 and concluded in March 2006.
Pre-assignment details
Participant Flow refers to the Intent-to-treat (ITT) population. 514 subjects were initially randomized, 4 subjects withdrew consent before first study drug intake.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (PBO) Placebo was administered as oral drops twice daily. | 255 |
| Levocetirizine (LCTZ) 0.125 mg/kg of Levocetirizine (LCTZ) were administered as oral drops twice daily. | 255 |
| Total Title | 510 |
| Total | 1,020 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 6 |
| Overall Study | Atopic dermatitis poorly controlled | 0 | 1 |
| Overall Study | Eczema deterioration | 0 | 1 |
| Overall Study | Eczema poorly controlled | 1 | 0 |
| Overall Study | Investigator decision | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 4 |
| Overall Study | Parent decision | 1 | 1 |
| Overall Study | Patient relocated | 1 | 0 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 21 | 22 |
Baseline characteristics
| Characteristic | Placebo (PBO) | Levocetirizine (LCTZ) | Total Title |
|---|---|---|---|
| Age, Categorical <=18 years | 255 Participants | 255 Participants | 510 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 19.42 months STANDARD_DEVIATION 3.86 | 19.28 months STANDARD_DEVIATION 3.94 | 19.35 months STANDARD_DEVIATION 3.9 |
| Sex: Female, Male Female | 91 Participants | 100 Participants | 191 Participants |
| Sex: Female, Male Male | 164 Participants | 155 Participants | 319 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 255 | 0 / 255 |
| other Total, other adverse events | 240 / 255 | 239 / 255 |
| serious Total, serious adverse events | 37 / 255 | 31 / 255 |
Outcome results
Primary
Time to Onset of Asthma During the Treatment Period
The time to onset of asthma was defined as the period elapsed between the randomization visit (V2) and the date of onset of asthma. Instead of the median the first Quartile is reported since the median (50%) was not reached.
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo (PBO) | Time to Onset of Asthma During the Treatment Period | NA months |
| Levocetirizine (LCTZ) | Time to Onset of Asthma During the Treatment Period | NA months |
p-value: =0.99195% CI: [0.75, 1.338]Regression, Cox
Secondary
Number of Episodes of Urticaria Per Subject
Urticaria was defined as typical hives or areas of skin swelling, redness and itching distinctly different from the child's usual inflamed skin lesions of Atopic Dermatitis (AD), associated with an infection or food allergen ingestion/contact or other trigger.
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) | Number of Episodes of Urticaria Per Subject | 1.71 Number of episodes | Standard Deviation 4.05 |
| Levocetirizine (LCTZ) | Number of Episodes of Urticaria Per Subject | 0.71 Number of episodes | Standard Deviation 1.83 |
Secondary
Percentage of Days of Use of Asthma Medication
The following asthma medications were taken into consideration: Beta 2-mimetics, cromoglycates, inhaled corticoids, systemic corticoids, leukotriene antagonists
Time frame: During the treatment period (18 months)
Population: 255 subject were included in the Intention-to-treat (ITT) set. Number of participants analyzed is given for each individual category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) | Percentage of Days of Use of Asthma Medication | Cromoglycates | 0.03 percentage of days | Standard Deviation 0.37 |
| Placebo (PBO) | Percentage of Days of Use of Asthma Medication | Systemic Corticoids | 0.31 percentage of days | Standard Deviation 1.02 |
| Placebo (PBO) | Percentage of Days of Use of Asthma Medication | Inhaled Corticoids | 3.60 percentage of days | Standard Deviation 12.03 |
| Placebo (PBO) | Percentage of Days of Use of Asthma Medication | Leukotriene antagonists | 0.30 percentage of days | Standard Deviation 2.19 |
| Placebo (PBO) | Percentage of Days of Use of Asthma Medication | Beta 2 Mimetics | 2.36 percentage of days | Standard Deviation 9.31 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Asthma Medication | Leukotriene antagonists | 0.34 percentage of days | Standard Deviation 3.23 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Asthma Medication | Beta 2 Mimetics | 1.37 percentage of days | Standard Deviation 4.47 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Asthma Medication | Cromoglycates | 0.09 percentage of days | Standard Deviation 1.24 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Asthma Medication | Inhaled Corticoids | 1.98 percentage of days | Standard Deviation 7.49 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Asthma Medication | Systemic Corticoids | 0.13 percentage of days | Standard Deviation 0.45 |
Secondary
Percentage of Days of Use of Medication for Atopic Dermatitis
The following medications for Atopic Dermatitis were taken into consideration: Emollients, local antihistamines; Local steroids class (LSC) A, non-steroidal anti-inflammatory (NSAI) creams, tar; Local steroids class B; Local steroids class C; Local antibiotics or antiseptics; Oral H1 anti-histamines (a-h); Local antibiotics (ABs) or antiseptics
Time frame: During the treatment period (18 months)
Population: 255 subject were included in the Intention-to-treat (ITT) set. Number of participants analyzed is given for each individual category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | Topical corticosteroids | 32.42 percentage of days | Standard Deviation 42.96 |
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | LSC A, NSAI creams, tar | 15.40 percentage of days | Standard Deviation 33.69 |
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | LSC B | 14.23 percentage of days | Standard Deviation 32.19 |
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | LSC C | 9.82 percentage of days | Standard Deviation 24.98 |
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | Topical tacrolimus | 0.36 percentage of days | Standard Deviation 5.41 |
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | Topical pimecrolimus | 0.52 percentage of days | Standard Deviation 5.62 |
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | Systemic H1 a-h | 3.80 percentage of days | Standard Deviation 14.28 |
| Placebo (PBO) | Percentage of Days of Use of Medication for Atopic Dermatitis | Local ABs or antiseptics | 2.99 percentage of days | Standard Deviation 15 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | Local ABs or antiseptics | 2.63 percentage of days | Standard Deviation 15.37 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | Topical corticosteroids | 31.84 percentage of days | Standard Deviation 42.7 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | Topical tacrolimus | 0.02 percentage of days | Standard Deviation 0.21 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | LSC A, NSAI creams, tar | 18.64 percentage of days | Standard Deviation 37.3 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | Systemic H1 a-h | 1.95 percentage of days | Standard Deviation 8.84 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | LSC B | 12.30 percentage of days | Standard Deviation 30.49 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | Topical pimecrolimus | 0.31 percentage of days | Standard Deviation 2.31 |
| Levocetirizine (LCTZ) | Percentage of Days of Use of Medication for Atopic Dermatitis | LSC C | 8.27 percentage of days | Standard Deviation 22.16 |
Secondary
Percentage of Days With Symptoms of Either Wheezing or Nocturnal Cough
The caring person was to note on the diary card each nocturnal cough event with sleep disturbances occurring from 7:00 pm to 7:00 am and each wheezing event occurring at any time together with the treatment for these symptoms.
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) | Percentage of Days With Symptoms of Either Wheezing or Nocturnal Cough | 3.5 percentage of days | Standard Deviation 6.26 |
| Levocetirizine (LCTZ) | Percentage of Days With Symptoms of Either Wheezing or Nocturnal Cough | 2.85 percentage of days | Standard Deviation 4.53 |
Secondary
Percentage of Days With Symptoms of Nocturnal Cough
The caring person was to note on the diary card each nocturnal cough event with sleep disturbances occurring from 7:00 pm to 7:00 am
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) | Percentage of Days With Symptoms of Nocturnal Cough | 2.72 percentage of days | Standard Deviation 5.24 |
| Levocetirizine (LCTZ) | Percentage of Days With Symptoms of Nocturnal Cough | 2.33 percentage of days | Standard Deviation 4.3 |
Secondary
Percentage of Days With Symptoms of Wheezing
The caring person was to note on the diary card each each wheezing event occurring at any time.
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PBO) | Percentage of Days With Symptoms of Wheezing | 1.31 percentage of days | Standard Deviation 3 |
| Levocetirizine (LCTZ) | Percentage of Days With Symptoms of Wheezing | 0.88 percentage of days | Standard Deviation 1.87 |
Secondary
Percentage of Subjects Using Asthma Medication
The following asthma medications were taken into consideration: Beta 2-mimetics, cromoglycates, inhaled corticoids, systemic corticoids, leukotriene antagonists
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (PBO) | Percentage of Subjects Using Asthma Medication | Leukotriene antagonists | 2.7 percentage of participants |
| Placebo (PBO) | Percentage of Subjects Using Asthma Medication | Beta 2 Mimetics | 33.3 percentage of participants |
| Placebo (PBO) | Percentage of Subjects Using Asthma Medication | Cromoglycates | 0.8 percentage of participants |
| Placebo (PBO) | Percentage of Subjects Using Asthma Medication | Inhaled Corticoids | 18.8 percentage of participants |
| Placebo (PBO) | Percentage of Subjects Using Asthma Medication | Systemic Corticoids | 18.4 percentage of participants |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Asthma Medication | Systemic Corticoids | 12.5 percentage of participants |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Asthma Medication | Inhaled Corticoids | 15.3 percentage of participants |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Asthma Medication | Beta 2 Mimetics | 33.3 percentage of participants |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Asthma Medication | Leukotriene antagonists | 3.5 percentage of participants |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Asthma Medication | Cromoglycates | 1.2 percentage of participants |
Secondary
Percentage of Subjects Using Medication for Atopic Dermatitis
The following medications for Atopic Dermatitis were taken into consideration: Topical corticosteroids/ Local Steroids Class A, non-steroidal anti-inflammatory (NSAI) creams, tar/ Local Steroids Class B/ Local Steroids Class C/ Topical tacrolimus/ Topical pimecrolimus/ Systemic H1 anti-histamines/ Local antibiotics or antiseptics
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Topical corticosteroids | 61.6 percentage of subjects |
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local Steroids Class A, NSAI creams, tar | 31.4 percentage of subjects |
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local Steroids Class B | 28.6 percentage of subjects |
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local Steroids Class C | 33.7 percentage of subjects |
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Topical tacrolimus | 0.8 percentage of subjects |
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Topical pimecrolimus | 2.4 percentage of subjects |
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Systemic H1 anti-histamines | 22.0 percentage of subjects |
| Placebo (PBO) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local antibiotics or antiseptics | 12.9 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local antibiotics or antiseptics | 11.0 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Topical corticosteroids | 63.9 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Topical tacrolimus | 1.2 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local Steroids Class A, NSAI creams, tar | 33.3 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Systemic H1 anti-histamines | 19.6 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local Steroids Class B | 27.1 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Topical pimecrolimus | 5.5 percentage of subjects |
| Levocetirizine (LCTZ) | Percentage of Subjects Using Medication for Atopic Dermatitis | Local Steroids Class C | 37.3 percentage of subjects |
Secondary
Percentage of Subjects With Urticaria
Urticaria was defined as typical hives or areas of skin swelling, redness and itching distinctly different from the child's usual inflamed skin lesions of Atopic Dermatitis (AD), associated with an infection or food allergen ingestion/contact or other trigger.
Time frame: During the treatment period (18 months)
Population: Intention-to-treat (ITT) population, consisting of all randomized subjects who took at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (PBO) | Percentage of Subjects With Urticaria | 41.6 percentage of participants |
| Levocetirizine (LCTZ) | Percentage of Subjects With Urticaria | 27.5 percentage of participants |