Safety Study of Levocetirizine Oral Solution for Japanese Pediatrics

Study Overview
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Brief Summary
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To evaluate the safety of treatment with levocetirizine oral solution in pediatric patients aged form 6 months to 2 years old with allergic rhinitis or pruritus associated with the skin diseases.

Detailed Description
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This is a multi-center, open-labelled study to confirm the safety as main objective, and consisting of minimum 1-week screening period and 2-week treatment period. The subjects who meet the inclusion criteria are to be placed on one of the following two regimens according to their ages at the start of treatment period: once daily administration of levocetirizine at a dose of 1.25 mg (in the morning) to infants aged between 6 months and 1 year old (younger age group), and twice daily administration of levocetirizine at a dose of 1.25 mg (in the morning, in the evening before sleep) to infants aged between 1 year and 2 years old (older age group).

Official Title
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A Multi-Center, Open-labelled Study to Evaluate the Safety of Levocetirizine Hydrochloride Oral Solution in Children Aged 6 Months to 2 Years With Allergic Rhinitis or Pruritus Associated With the Skin Diseases.

Conditions
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Rhinitis

Intervention / Treatment
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* Drug: Levocetirizine
* Drug: Levocetirizine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients Either boys or girls are acceptable. Pediatric patients ranging from 6 months to 2 years in age at the time of initiation of the treatment in clinical trial Pediatric patients who have at least one of the symptoms associated with allergic rhinitis including rhinorrhea, nasal congestion and sneezing, and require at least 2-week treatment with antihistamine drugs, or those who suffer from pruritus associated with the following diseases and require at least 2-week treatment with antihistamine drugs (- Chronic urticaria, - Eczema/dermatitis group: atopic dermatitis etc. [A diagnosis of atopic dermatitis is made in accordance with the Definition/Diagnostic Criteria of Atopic Dermatitis, - Prurigo group: acute prurigo (strophulus, urticaria-like lichen, etc.), subacute prurigo, chronic prurigo (nodular prurigo etc.), - Pruritus cutaneous: systemic pruritus cutaneous, local pruritus cutaneous) Pediatric patients with QTc interval below 450 msec. QTc interval shall be below 480 msec in the pediatric patients with bundle branch block at screening (A judgment shall be made according to the QTc interval based on ECG result corresponding to one heart beat or the QTc interval based on the mean of ECG results corresponding to 3 heart beats.) AST<2×upper limit of normal, ALT<2×upper limit of normal, alkaline phosphatase≤1.5×upper limit of normal, bilirubin≤1.5×upper limit of normal at screening (The serum bilirubin shall be fractioned and the direct bilirubin shall be below 35%. In this case, the free bilirubin level exceeding 1.5 times the upper limit of normal is acceptable.) Pediatric patients whose parents (persons with parental authority or guardians) shall submit written informed consent Pediatric patients whose parents (persons with parental authority or guardians) shall fill the medication diaries Exclusion Criteria: Pediatric patients whose body weight is above or below the infantile growth curves shown in the infant body growth investigation report in 2011 [MHLW, 2011] Pediatric patients breast-fed by mothers who take any antihistamine drugs during the study period Pediatric patients who received systemic adrenocorticosteroids within 28 days before Visit 2 Pediatric patients who are currently treated or planned to have immunotherapy initiated during the study period Pediatric patients who had abnormal laboratory results that were unrelated to allergic disorders [These patients can be enrolled if the investigator (or sub-investigator) judges that their enrolment poses no clinical problem.] Pediatric patients who require application of adrenocorticosteroids for external use that are classified as strongest, very strong or strong Pediatric patients who suffer from asthma as a complication and require treatment with adrenocorticosteroids (including adrenocorticosteroid combinations) Pediatric patients with the history of convulsion, febrile convulsion or sleep apnea Pediatric patients whose brothers or sisters have history of sleep apnea or sudden infant death syndrome Pediatric patients with history of allergy or hypersensitivity to the ingredients of levocetirizine hydrochloride preparation or piperazine derivatives such as hydroxyzine, cetirizine, cyclizine Pediatric patients with history of drug hypersensitivity Pediatric patients who are considered inappropriate as the subjects of this clinical trial because of liver diseases, renal diseases, heart diseases or other complications that pose clinical problem Pediatric patients whose parents are minors Infants who belong to children's institutions Pediatric patients who participated in other clinical trials for 6 months before enrolment or those who intend to participate in other clinical trials during the clinical trial period. Person meeting any of the following criteria and his/her family (- An employee of GlaxoSmithKline K.K., - Investigator or sub-investigator, - An employee of Site Management Organization (SMO) related with the clinical study) Other pediatric patients who are judged as inappropriate for participating in this clinical trial by the investigator (or sub-investigator)

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 23 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levocetirizine<br>Clear solution, 0.50 mg levocetirizine dihydrochloride contains in one milliliter of the solution | Drug: Levocetirizine<br>* Clear solution, 0.50 mg levocetirizine dihydrochloride contains in one milliliter of the solution. Levocetirizine oral solution are administered once daily at a dose of 2.5 mL (1.25 mg of levocetirizine) in the morning to infants aged between 6 months and 1 year old<br>Drug: Levocetirizine<br>* Clear solution, 0.50 mg levocetirizine dihydrochloride contains in one milliliter of the solution. Levocetirizine oral solution are administered twice daily at a dose of 2.5 mL (1.25 mg of levocetirizine) in the morning and evening before sleep to infants aged between 1 year and 2 years old<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs) | A non-serious AE is defined as any untoward medical occurrence in a participant/clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse, or misuse. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is a possible drug-induced liver injury. For a list of all SAEs/non-serious AEs occurring at a frequency of >=5%, please see the SAE/non-serious AE module of this record. | up to Week 2/Early Withdrawal (EW) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With the Indicated Change From the First Day of Treatment in Allergic Rhinitis and Pruritis Associated With Skin Diseases at Weeks 1 and 2/EW, as Assessed by the Investigator/Sub-investigator Based on Legal Representative Impression | The investigator or sub-investigator made an overall assessment of nasal symptoms (allergic rhinitis [AR]) and pruritus associated with skin diseases (PAWSD) at Weeks 1 and 2 (or at the discontinuation day in the case of early withdrawal [EW] from the clinical trial) by asking the participants' legal representatives to provide feedback using the following scale: 1, significantly improved; 2, moderately improved; 3, mildly improved; 4, no change; 5, mildly worse; 6, moderately worse; 7, significantly worse. Only those participants with AR and PAWSD at Baseline were assessed for improvement in the conditions at Weeks 1 and 2. The ns in the category titles reflect the number of participants in the Full Analysis Set (FAS) who had AR and PAWSD at Baseline. | First day of treatment; Weeks 1 and 2/Early Withdrawal | 
| Number of Participants With the Indicated Change From the First Day of Treatment in Nasal Symptoms and Pruritis Associated With Skin Diseases at Weeks 1 and 2/Early Withdrawal, as Assessed by the Investigator or Sub-investigator | The investigator or sub-investigator comprehensively assessed the participants' improvement in nasal symptoms (allergic rhinitis [AR]) and pruritus associated with skin diseases (PAWSD) at Weeks 1 and 2 (or at the discontinuation day in the case of early withdrawal [EW] from the clinical trial) compared to the first day of treatment by using the following scale: 1, markedly improved; 2, moderately improved; 3, slightly improved; 4, no change; 5, worsened. | First day of treatment; Weeks 1 and 2/Early Withdrawal | 
| Number of Participants Categorized With the Indicated Pruritis Severity on the First Day of Treatment and at Weeks 1 and 2/Early Withdrawal | The investigator comprehensively assessed the pariticipant's severity of pruritus on the first day of treatment (FDOT), at Week 1, and at Week 2 (or at the discontinuation day in the case of early withdrawal [EW] from the clinical trial) by using the following scale: 4, severe; 3, moderate; 2, mild; 1, slight; 0, none. | First day of treatment; Weeks 1 and 2/Early Withdrawal | 
| Cmax and Cmin of Levocetirizine in Plasma | Cmax is defined as the peak plasma concentration of a drug after administration. Cmin is defined as the lowest (trough) concentration that a drug reaches before the next dose is administered. For both age cohorts, blood samples were collected 1.5-2.5 hours after the last drug administration for assessment of Cmax at either Week 1 or 2/EW. For participants in the >=6 months and <12 months cohort, blood samples were collected 22.5-25.5 hours after the last drug administration for Cmin at a different visit from Cmax sampling. For participants in the >=12 months and <24 months cohort, blood samples were collected 10.5-13.5 hours after the final drug administration for Cmin at a different visit from Cmax sampling. For all participants, if Cmin sampling occurred at Week 1, then Cmax sampling occurred at Week 2/EW, and vice versa. | Weeks 1 and 2/Early Withdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allergic rhinitis, Pediatric, Pruritus, Levocetirizine