Safety Study of Levocetirizine Dihydrochloride Oral Liquid Formulation in Children Aged 1 to Less Than 6 Years Suffering From Allergic Rhinitis or Chronic Urticaria of Unknown Origin

A Multi-Center, Randomized, Double Blind, Placebo Controlled Parallel Group Study of the Safety of Levocetirizine Dihydrochloride Oral Liquid Formulation b.i.d Dosing in Children Aged 1 to < 6 Years Suffering From Allergic Rhinitis or Chronic Urticaria of Unknown Origin

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00619801

Acronym

PAL

Enrollment

173

Registered

2008-02-21

Start date

2008-03-31

Completion date

2008-07-31

Last updated

2015-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Allergic Rhinitis, Chronic Urticaria

Keywords

Xyzal, Levocetirizine, Allergy, Children, Seasonal Allergies

Brief summary

The purpose of this study is to determine the safety of the oral formulation of levocetirizine in children ages 1 to less than 6 years old who suffer from allergic rhinitis or chronic urticaria of unknown origin.

Interventions

DRUGLevocetirizine

Levocetirizine dihydrochloride 1.25 mg oral drops formulation (5 drops containing 5mg/mL) dosed twice a day for 2 weeks

DRUGPlacebo

Placebo oral drops (5 drops) dosed twice a day for 2 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

2 Years to 6 Years

Healthy volunteers

Inclusion criteria

* Outpatient, male or female pediatric subject, ages 1 to less than 6 years old at the Randomization Visit (V2) (1 - \< 6 years old) * The subject must present at least one of the following symptoms, most commonly associated with allergic rhinitis or chronic urticaria: nasal itching, sneezing, rhinorrhea, nasal congestion, tearing, eye redness and itching of eyes, ears and/or palate, skin wheals and itching of the skin * Subjects (age 2 to less than 6 years only) suffering from allergic rhinitis (AR) should have a documented allergy measured by positive skin prick test or RAST (Radioallergosorbent Test) performed within the last 6 months prior to randomization * Candidate for antihistamine treatment or received antihistamine in the past for similar symptoms as those presenting * Caregiver(s) have been informed of the nature and aims of the study and have given their written informed consent for the subject to participate in this study * Caregiver(s) able to understand information given, the text of the informed consent, and be able to complete the daily record card (DRC)

Exclusion criteria

* Any clinically significant medical condition or abnormality other than the primary diagnosis for which an antihistamine is indicated * Be initiating or changing the dose of an immunotherapy regimen during the course of the study (Visit 1 to Visit 4) * Any electrocardiogram (ECG) parameters, including a QTcF interval \> 443 msec measured by an ECG obtained at the Screening Visit, outside the normal reference ranges * Any clinical laboratory tests performed at the Screening Visit, other than those related with the allergic condition, outside the reference ranges. Subjects having values outside the accepted reference range can be included if in the Investigator's opinion, they are of no clinical significance * Personal history of seizure, febrile seizure or sleep apnea * Below the lower 5th or above 95th percentile for body weight and/or height based upon CDC Growth Charts for Body Weight and Length * Allergy or intolerance to levocetirizine dihydrochloride or its excipients, or to any other piperazine derivatives, such as hydroxyzine, cetirizine, cyclizine, meclozine, buclizine * Current or past intake of the following medications (including exposure through breast milk) within the specified wash-out period before the Randomization Visit (V2): 1. Systemic corticosteroids within the past 28 days 2. Leukotriene-receptor antagonists (e.g. montelukast \[Singulair\] or zafirlukast \[Accolate\] within the past 7 days) 3. Mast-cell stabilizers (e.g. cromolyn or nedocromil) within the past 7 days 4. Other antihistamines or cough and cold preparations (with the exception of single ingredient guaifenesin products) or over-the-counter (OTC) sleep aid medications within the past 7 days 5. Systemic antibiotics within the past 7 days 6. Other concomitant medications that will interfere with the study, in the opinion of the investigator * Previous participation in another clinical/pharmacological trial within the past month prior to V1 * Have already participated in this study or participated in this study at another site * Children of any member of the study site staff

Design outcomes

Primary

Measure	Time frame	Description
Absolute Value of QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV)	14 days	The QT interval refers to the respective time interval in the Electrocardiogram (ECG).
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in PR Interval	Baseline, 14 days	The PR interval refers to the respective time interval in the Electrocardiogram (ECG).
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in QRS Duration	Baseline, 14 days	The QRS duration refers to the respective time duration in the Electrocardiogram (ECG).
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in QT Interval	Baseline, 14 days	The QT interval refers to the respective time interval in the Electrocardiogram (ECG).
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF)	Baseline, 14 days	The QT interval refers to the respective time interval in the Electrocardiogram (ECG).
Absolute Value of QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) at Visit 3 (Day 7)	7 days	The QT interval refers to the respective time interval in the Electrocardiogram (ECG).
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in Ventricular Rate (VR)	Baseline, 14 days	—
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in RR Interval	Baseline, 14 days	The RR interval refers to the respective time interval in the Electrocardiogram (ECG).

Secondary

Measure	Time frame
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in Alanine Aminotransferase (ALT)	Baseline, 14 days
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in Aspartate Aminotransferase (AST)	Baseline, 14 days
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in Blood Urea Nitrogen	Baseline, 14 days
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in Blood Creatinine	Baseline, 14 days
Change From Baseline at Visit 4 (Day 14) or at Early Discontinuation Visit (EDV) in Total Bilirubin	Baseline, 14 days

Countries

United States

Participant flow

Participants by arm

Arm	Count
Placebo Placebo (5 drops) dosed by mouth at breakfast time and in the evening (the evening dose should be administered approximately 12 hours later), twice a day for 2 weeks from Visit 2 (Day 0) to Visit 4 (Day 14) or the Early Discontinuation Visit (EDV).	59
Levocetirizine Levocetirizine dihydrochloride 1.25 mg (5 drops containing 5 mg/mL) dosed by mouth at breakfast time and in the evening (the evening dose should be administered approximately 12 hours later), twice a day for 2 weeks from Visit 2 (Day 0) to Visit 4 (Day 14) or the Early Discontinuation Visit (EDV).	114
Total	173

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lack of Efficacy	0	1
Overall Study	Loss of efficacy	0	1
Overall Study	Withdrawal by Subject	1	1

Baseline characteristics

Characteristic	Levocetirizine	Placebo	Total
Age, Categorical <=18 years	114 Participants	59 Participants	173 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	3.78 years STANDARD_DEVIATION 1.38	3.75 years STANDARD_DEVIATION 1.45	3.77 years STANDARD_DEVIATION 1.4
Region of Enrollment United States	114 participants	59 participants	173 participants
Sex: Female, Male Female	49 Participants	23 Participants	72 Participants
Sex: Female, Male Male	65 Participants	36 Participants	101 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	21 / 59	39 / 114
serious Total, serious adverse events	0 / 59	1 / 114

Outcome results

Primary