Dermatitis, Eczema
Conditions
Keywords
Dermatitis, Eczema, Pruritus, Xyzal, Zyrtec, Levocetirizine, Cetirizine
Brief summary
Korean double-blind non-inferiority study to asses the efficacy (as measured by the responder rate of pruritus severity score by the patient at visit 4 or end-of-treatment visit over the 2 weeks treatment period) and safety of Xyzal® to Zyrtec® in subjects suffering from dermatitis and eczema with pruritus symptoms
Interventions
DRUGLevocetirizine
1 Levocetirizine 5mg tablet per day before bedtime for 14 days
DRUGCetirizine
1 Cetirizine 10mg tablet per day before bedtime for 14 days.
DRUGPlacebo-Levocetirizine
1 Placebo-Levocetirizine tablet per day before bedtime for 14 days
DRUGPlacebo-Cetirizine
1 Placebo-Cetirizine tablet per day before bedtime for 14 days
DRUGStandard topical steroid (1% hydrocortisone) ointment
1% hydrocortisone ointment, applied 2-3 times a day to all affected areas
Sponsors
UCB Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects diagnosed as having atopic dermatitis, contact dermatitis, prurigo, pruritus in the dermatitis and eczema * Subjects who require and agree to the concomitant use of a topical steroid preparation. * Subjects having a minimum level of pruritus and having used topical hydrocortisone during the run -in period * Written informed consent signed and dated by subject/legal guardian * Female subjects with childbearing potential are eligible if they use a medically accepted contraceptive method and have a negative pregnancy test.
Exclusion criteria
* Subjects with a known hypersensitivity to cetirizine or levocetirizine * Any clinically significant condition that might interfere with the treatment evaluation, both for efficacy and safety * Have used forbidden concomitant medications or having not respected adequate wash-out periods as defined by the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score). | Day 7 and 14 | A participant is a responder if the pruritus severity score is assessed as mild or none, otherwise it is a non-responder. The responder status is defined at day 14, except if the investigator assessed the subject as a responder at day 7. The Pruritus Score is in general defined as: 3 for Severe, 2 for Moderate, 1 for Mild and 0 for None. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mean Pruritus Severity Score at Endpoint During the 14 Day Treatment Period | Baseline and at endpoint during the 14 day treatment period | The Pruritus Score Scale ranges from 0 to 3 (3 for Severe, 2 for Moderate, 1 for Mild and 0 for None). Endpoint is at visit 4 on day 14 or at an earlier timepoint at study completion. |
| Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period | At endpoint during the 14 day treatment period | Duration of pruritus was categorized as follows: 3 if \> 6 hours/24hr, 2 if 1 to 6 hours/24hr, 1 if less than 1 hour/24hr, and 0 if No pruritus. The endpoint is visit 4 on day 14 or at an earlier time point at study completion. |
| Global Improvement at Endpoint During the 14 Day Treatment Period | At endpoint during the 14 day treatment period | Global improvement is measured on an ordered nominal scale ranging from marked improvement to exacerbation (see categories in the table). The endpoint is visit 4 on day 14 or at an earlier time point at study completion. |
Countries
South Korea
Participant flow
Recruitment details
506 patients were screened and 466 randomized. Due to a packaging error 99 patients were excluded from the efficacy analysis according to the advice of the Korean FDA. The Reported Adverse Events section refers to the Safety Population (N= 423) defined as all patients treated with at least one safety evaluation without entry criteria violation.
Pre-assignment details
Participant workflow refers to all randomized subjects whereas in Baseline Characteristics numbers and statistics for the modified Intent To Treat (m-ITT) population are presented (see definition of m-ITT population in the Outcome Measure section).
Participants by arm
| Arm | Count |
|---|---|
| Levocetirizine Levocetirizine 5 mg tablet once daily plus Placebo - Cetirizine 10 mg tablet once daily plus standard topical steroid ointment | 168 |
| Cetirizine Cetirizine 10 mg tablet once daily plus Placebo - Levocetirizine 5 mg once daily plus standard topical steroid ointment | 172 |
| Total | 340 |
Baseline characteristics
| Characteristic | Levocetirizine | Cetirizine | Total |
|---|---|---|---|
| Age Continuous | 30.17 years STANDARD_DEVIATION 10.09 | 30.11 years STANDARD_DEVIATION 10.6 | 30.14 years STANDARD_DEVIATION 10.34 |
| Region of Enrollment Korea, Republic of | 168 participants | 172 participants | 340 participants |
| Sex: Female, Male Female | 113 Participants | 120 Participants | 233.0 Participants |
| Sex: Female, Male Male | 55 Participants | 52 Participants | 107.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 209 | 5 / 214 |
| serious Total, serious adverse events | 1 / 209 | 0 / 214 |
Outcome results
Primary
Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score).
A participant is a responder if the pruritus severity score is assessed as mild or none, otherwise it is a non-responder. The responder status is defined at day 14, except if the investigator assessed the subject as a responder at day 7. The Pruritus Score is in general defined as: 3 for Severe, 2 for Moderate, 1 for Mild and 0 for None.
Time frame: Day 7 and 14
Population: The modified ITT population is defined as all randomized patients who received the study drug, except the patients who did not meet the entry criteria, took prohibited medication during the study period, did not have any available data for efficacy evaluation and who were enrolled with packing errors.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levocetirizine | Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score). | Responder | 131 Participants |
| Levocetirizine | Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score). | Non-Responder | 37 Participants |
| Cetirizine | Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score). | Responder | 134 Participants |
| Cetirizine | Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score). | Non-Responder | 38 Participants |
Comparison: The lower bound of the 95% two sided confidence interval for the difference (Levocetirizine - Cetirizine) in percentage of responders is compared to the pre-set threshold for non inferiority (-10% which is equal to -0.1 for the proportion of responders). Standard method for estimation of the difference in proportions incl. confidence interval using normal approximation is used.95% CI: [-0.0875, 0.0888]
Secondary
Change From Baseline in the Mean Pruritus Severity Score at Endpoint During the 14 Day Treatment Period
The Pruritus Score Scale ranges from 0 to 3 (3 for Severe, 2 for Moderate, 1 for Mild and 0 for None). Endpoint is at visit 4 on day 14 or at an earlier timepoint at study completion.
Time frame: Baseline and at endpoint during the 14 day treatment period
Population: All patients in modified Intent-to-treat population. Last Observation Carried Forward principle was applied to the missing data of the pruritus severity score on the previous day of the randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levocetirizine | Change From Baseline in the Mean Pruritus Severity Score at Endpoint During the 14 Day Treatment Period | 1.15 Units on a scale | Standard Error 0.05 |
| Cetirizine | Change From Baseline in the Mean Pruritus Severity Score at Endpoint During the 14 Day Treatment Period | 1.21 Units on a scale | Standard Error 0.05 |
Comparison: The mean daily pruritus score at Day 14 visit or at study completion was analyzed using an analysis of covariance (ANCOVA) model, including pruritus severity score of the day before the randomization as a covariate and treatment group as a factorp-value: 0.4369ANCOVA
Secondary
Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period
Duration of pruritus was categorized as follows: 3 if \> 6 hours/24hr, 2 if 1 to 6 hours/24hr, 1 if less than 1 hour/24hr, and 0 if No pruritus. The endpoint is visit 4 on day 14 or at an earlier time point at study completion.
Time frame: At endpoint during the 14 day treatment period
Population: All patients in modified Intent-to-treat population. Last Observation Carried Forward principle was applied to the missing data of the pruritus severity score on the previous day of the randomization.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levocetirizine | Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period | 2.13 Units on a scale | Standard Error 0.05 |
| Cetirizine | Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period | 2.20 Units on a scale | Standard Error 0.05 |
Comparison: The categorized duration of Pruritus at endpoint during the 14 day treatment period was analyzed using an analysis of covariance (ANCOVA) model, including pruritus severity score of the day before the randomization as a covariate and treatment group as a factor.p-value: 0.3549ANCOVA
Secondary
Global Improvement at Endpoint During the 14 Day Treatment Period
Global improvement is measured on an ordered nominal scale ranging from marked improvement to exacerbation (see categories in the table). The endpoint is visit 4 on day 14 or at an earlier time point at study completion.
Time frame: At endpoint during the 14 day treatment period
Population: All patients in modified ITT except 1 patient in levocetirizine group and 3 patients in cetirizine group who have missing values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levocetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Moderate improvement | 62 Participants |
| Levocetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | No change | 18 Participants |
| Levocetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Mild improvement | 39 Participants |
| Levocetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Exacerbation | 1 Participants |
| Levocetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Marked improvement | 47 Participants |
| Cetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Exacerbation | 1 Participants |
| Cetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Marked improvement | 52 Participants |
| Cetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Moderate improvement | 54 Participants |
| Cetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | Mild improvement | 47 Participants |
| Cetirizine | Global Improvement at Endpoint During the 14 Day Treatment Period | No change | 15 Participants |
p-value: 0.7518Cochran-Mantel-Haenszel