Randomized Phase III Study to Evaluate the Efficacy and Safety of Xyzal® (Levocetirizine) vs Zyrtec® (Cetirizine) in Subjects With Dermatitis and Eczema - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment
Conditions:	Dermatitis Eczema
Interventions:	Drug: Levocetirizine Drug: Cetirizine Drug: Placebo-Levocetirizine Drug: Placebo-Cetirizine Drug: Standard topical steroid (1% hydrocortisone) ointment

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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).

Reporting Groups

	Description
Levocetirizine	Levocetirizine 5 mg tablet once daily plus Placebo - Cetirizine 10 mg tablet once daily plus standard topical steroid ointment
Cetirizine	Cetirizine 10 mg tablet once daily plus Placebo - Levocetirizine 5 mg once daily plus standard topical steroid ointment

Participant Flow: Overall Study

	Levocetirizine	Cetirizine
STARTED	232^[1]	234^[2]
COMPLETED	212^[3]	211^[4]
NOT COMPLETED	20	23

[1]	Randomized population (N=232).
[2]	Randomized population (N=234).
[3]	20 Patients were not treated or discontinued after randomization in Levocetirizine group.
[4]	23 Patients were not treated or discontinued after randomization in Cetirizine group.

Baseline Characteristics

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Reporting Groups

	Description
Levocetirizine	Levocetirizine 5 mg tablet once daily plus Placebo - Cetirizine 10 mg tablet once daily plus standard topical steroid ointment
Cetirizine	Cetirizine 10 mg tablet once daily plus Placebo - Levocetirizine 5 mg once daily plus standard topical steroid ointment

Baseline Measures

	Levocetirizine	Cetirizine	Total
Number of Participants [units: participants]	168	172	340
Age [units: years] Mean ± Standard Deviation	30.17 ± 10.09	30.11 ± 10.60	30.14 ± 10.34
Gender [units: participants]
Female	113	120	233
Male	55	52	107
Region of Enrollment [units: participants]
Korea, Republic of	168	172	340

Outcome Measures

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1. Primary:

Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score). [ Day 7 and 14 ]

Measure Type	Primary
Measure Title	Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score).
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Levocetirizine	Levocetirizine 5 mg tablet once daily plus Placebo - Cetirizine 10 mg tablet once daily plus standard topical steroid ointment
Cetirizine	Cetirizine 10 mg tablet once daily plus Placebo - Levocetirizine 5 mg once daily plus standard topical steroid ointment

Measured Values

	Levocetirizine	Cetirizine
Number of Participants Analyzed [units: participants]	168	172
Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score). [units: Participants]
Responder	131	134
Non-Responder	37	38

Statistical Analysis 1 for Responder Status According to Pruritus Severity Score (Response = Mild or None in Pruritus Severity Score).

Groups ^[1]	All groups
Non-Inferiority/Equivalence Test ^[2]	Yes
Difference in proportion of responders ^[3]	0.00069213
95% Confidence Interval	( -0.0875 to 0.0888 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	The pre-set threshold for non inferiority is -10%.
[3]	Other relevant estimation information:
	No text entered.

2. Secondary:

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 ]

Measure Type	Secondary
Measure Title	Change From Baseline in the Mean Pruritus Severity Score at Endpoint During the 14 Day Treatment Period
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Levocetirizine	Levocetirizine 5 mg tablet once daily plus Placebo - Cetirizine 10 mg tablet once daily plus standard topical steroid ointment
Cetirizine	Cetirizine 10 mg tablet once daily plus Placebo - Levocetirizine 5 mg once daily plus standard topical steroid ointment

Measured Values

	Levocetirizine	Cetirizine
Number of Participants Analyzed [units: participants]	168	172
Change From Baseline in the Mean Pruritus Severity Score at Endpoint During the 14 Day Treatment Period [units: Units on a scale] Mean ± Standard Error	1.15 ± 0.05	1.21 ± 0.05

Statistical Analysis 1 for Change From Baseline in the Mean Pruritus Severity Score at Endpoint During the 14 Day Treatment Period

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.4369

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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 factor
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Pruritus score is adjusted on pruritus Baseline score.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

3. Secondary:

Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period [ At endpoint during the 14 day treatment period ]

Measure Type	Secondary
Measure Title	Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Levocetirizine	Levocetirizine 5 mg tablet once daily plus Placebo - Cetirizine 10 mg tablet once daily plus standard topical steroid ointment
Cetirizine	Cetirizine 10 mg tablet once daily plus Placebo - Levocetirizine 5 mg once daily plus standard topical steroid ointment

Measured Values

	Levocetirizine	Cetirizine
Number of Participants Analyzed [units: participants]	168	172
Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period [units: Units on a scale] Mean ± Standard Error	2.13 ± 0.05	2.20 ± 0.05

Statistical Analysis 1 for Duration of Pruritus (Stated in Categories) at Endpoint During the 14 Day Treatment Period

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.3549

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	pruritus severity score at baseline has been used as a covariate.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

4. Secondary:

Global Improvement at Endpoint During the 14 Day Treatment Period [ At endpoint during the 14 day treatment period ]

Measure Type	Secondary
Measure Title	Global Improvement at Endpoint During the 14 Day Treatment Period
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All patients in modified ITT except 1 patient in levocetirizine group and 3 patients in cetirizine group who have missing values.

Reporting Groups

	Description
Levocetirizine	Levocetirizine 5 mg tablet once daily plus Placebo - Cetirizine 10 mg tablet once daily plus standard topical steroid ointment
Cetirizine	Cetirizine 10 mg tablet once daily plus Placebo - Levocetirizine 5 mg once daily plus standard topical steroid ointment

Measured Values

	Levocetirizine	Cetirizine
Number of Participants Analyzed [units: participants]	167	169
Global Improvement at Endpoint During the 14 Day Treatment Period [units: Participants]
Marked improvement	47	52
Moderate improvement	62	54
Mild improvement	39	47
No change	18	15
Exacerbation	1	1

Statistical Analysis 1 for Global Improvement at Endpoint During the 14 Day Treatment Period

Groups ^[1]	All groups
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.7518

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	stratified on the prurity severity score at the previous day of randomization.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: UCB Clinical Trial Call Center
Organization: UCB Pharma
phone: + 1 877 822 9493

No publications provided

Responsible Party:	UCB ( Study Director )
Study ID Numbers:	A00410
Study First Received:	September 12, 2006
Results First Received:	July 8, 2009
Last Updated:	September 11, 2009
ClinicalTrials.gov Identifier:	NCT00375713 History of Changes
Health Authority:	Korea: Food and Drug Administration