Randomized, Double Blind, Parallel Group, Placebo Controlled, Multi-Center Study of the Efficacy and Safety of Cetirizine HCl Syrup vs. Loratadine Syrup vs. Placebo in Treatment of Children With Seasonal Allergic Rhinitis (SAR)

Brief Title

Randomized, Double Blind, Parallel Group, Placebo Controlled, Multi-Center Study of the Efficacy and Safety of Cetirizine HCl Syrup vs. Loratadine Syrup vs. Placebo in Treatment of Children With Seasonal Allergic Rhinitis (SAR)

Official Title

Randomized, Double Blind, Parallel Group, Placebo Controlled, Multi-Center Study of the Efficacy and Safety of Zyrtec® (Cetirizine HCl) Syrup vs. Claritin® (Loratadine) Syrup vs. Placebo in Treatment of Children With Seasonal Allergic Rhinitis (SAR)

Brief Summary

      The objective of this clinical trial was to assess the efficacy and safety of cetirizine HCl
      syrup vs. loratadine syrup vs. placebo syrup in the treatment of SAR in children 6 to 11
      years old.
    

Detailed Description

      This was a multi-center, randomized, double-blind, parallel-group, placebo-controlled, double
      dummy study of children with SAR conducted during the Spring tree and grass allergy season.
      Subjects qualified for randomization if the diary cards included (1) symptom scores of ≥2 for
      at least 2 of the following 4 rhinoconjunctivitis symptoms on 4 or more days: sneezing, runny
      nose, itchy eyes, and watery eyes; and (2) a total rhinoconjunctivitis (or Total Symptom
      Severity Complex [TSSC]) score of ≥5 on any 4 days. The TSSC score was expressed as the sum
      of the 4 individual symptoms scores recorded in the daily diary cards for the following
      symptoms: sneezing, runny nose, itchy eyes, and watery eyes.

      Subjects were randomized to receive 1 of 3 treatments in a double-blind fashion using a 1:1:1
      allocation ratio: cetirizine HCl syrup and placebo loratadine syrup; loratadine syrup and
      placebo cetirizine HCl syrup; or cetirizine placebo syrup and loratadine placebo syrup.

      Number of Subjects (Planned and Analyzed): 1100 planned; 1536 screened; 683 randomized: 231
      (33.8%) randomized to the cetirizine HCl treatment group, 221 (32.4%) to the loratadine
      treatment group, and 231 (33.8%) to the placebo treatment group.

      Test Product and Reference Therapy: Subjects randomized to receive cetirizine HCl syrup also
      received placebo syrup; subjects randomized to receive loratadine syrup also received placebo
      syrup; and both placebo syrups were received by subjects randomized to receive placebo.

      Duration of Double-Blind Treatment: 2 weeks.

      Safety measures included the incidence and severity of treatment-emergent adverse events
      (AEs), vital signs, concomitant medications, and physical examination findings. Clinical
      laboratory evaluation was not required for this study.

      Statistical Methods: All statistical tests related to treatment effect were 2-sided, and
      statistical significance was declared at the 0.05 probability level. Least squares means
      (LSMeans) were used to estimate treatment effect. Populations analyzed included the Full
      Analysis (intent-to-treat [ITT]) Set (FAS), Per-Protocol Set (PPS), Safety-Analyzable Set,
      and All-Screened Analysis Set. Demographic and baseline data for all subjects in the
      Safety-Analyzable Set were summarized and listed. The effects of treatment at the Overall and
      all other analysis Time Points were assessed using ANCOVA models. The main effects model
      contained terms for treatment and Investigator site, with baseline TSSC value as a covariate.
      The LSMeans and standard errors were based on the main effects model. Methods of analysis of
      secondary efficacy data included analysis of covariance (ANCOVA) models and
      Cochran-Mantel-Haenszel (CMH) row mean scores tests. Analysis of drug safety included the
      incidence of treatment-emergent AEs (TEAE), concomitant medications, vital signs, and
      physical examination findings for the Safety-Analyzable Set.
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Change from baseline to the Overall endpoint in the subject 24-hour reflective total symptom severity complex (TSSC) score

Secondary Outcome

 Change from baseline to the Overall endpoint in the subject 24-hour reflective TSSC, with and without stuffy nose score

Condition

Allergic Rhinitis

Intervention

Cetirizine

Study Arms / Comparison Groups

 Cetirizine 10 mg
Description:  Cetirizine HCl 10 mg (1 mg/ml) syrup once daily for 2 weeks. Subjects who were randomized to receive cetirizine HCl syrup also received placebo syrup. Each subject was instructed to take 2 teaspoons from Bottle A and 2 teaspoons from Bottle B once daily, before 10:00 AM.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

683

Start Date

March 2001

Completion Date

July 2001

Primary Completion Date

July 2001

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female 6 to 11 years of age.

          -  Females who reached menarche either before or during the study, agreed to use
             acceptable methods of birth control if they became sexually active. Acceptable birth
             control was defined as oral contraceptives or Norplant®.

          -  Outpatient.

          -  History and diagnosis of seasonal allergic rhinitis (SAR) to a prevalent allergen
             (grass or tree).

          -  SAR to a prevalent allergen (grass or tree) of such severity that it required
             pharmacologic therapy each year for the last 2 consecutive years (including the
             present year).

          -  Documented SAR to a prevalent allergen (grass or tree) as confirmed by a recognized
             skin test (prick, intradermal [ID], or Multitest®) within the previous 15 months
             (Prick/Puncture wheal® ≥3 mm over the negative control; ID [up to concentration of
             1:1000 w/v or 1000 protein nitrogen units (PNU)] wheal® ≥5 mm over the negative
             control). Documentation of SAR must have occurred at Visit 1 or within 15 months prior
             to Visit 1. If not performed at Visit 1, SAR testing must have been performed in the
             Principal Investigator's office or full documentation must have been available prior
             to randomization.

          -  Diary-recorded rhinoconjunctivitis symptom scores (24 hour reflective) that included
             at least two symptoms (sneezing, runny nose, itchy eyes, or watery eyes) at moderate
             severity (i.e., symptom score ≥2) on at least 4 days between Visits 1 and 2.

          -  Diary-recorded TSSC score ≥5 (based on the four symptoms noted in the criteria above)
             on any 4 days between Visits 1 and 2.

          -  Someone (subject and parent/legal guardian) from whom the Principal Investigator or
             study personnel would have expected conscientious cooperation over the duration of the
             study.

          -  A written informed assent must have been provided by the subject and a written
             informed consent must have been provided by the parent/legal guardian at Visit 1.

        Exclusion Criteria:

          -  Had clinically significant nasal anatomical deformities with > 50% obstruction (i.e.,
             septal defects, polyps).

          -  Experienced an episode of acute sinusitis or an upper respiratory tract infection
             (URTI) including otitis media and the common cold) within 21 days of Visit 1.

          -  Had a history of chronic sinusitis.

          -  Initiated or advanced an immunotherapy regimen during the course of the study.
             Subjects receiving a maintenance dose of immunotherapy were eligible.

          -  Had a history of attention deficit/hyperactivity disorder (ADHD) that was considered
             unstable by the Investigator, or if pharmacotherapy (i.e., Ritalin®, Adderall®) was
             required, subject must have been on pharmacotherapy for at least 1 month prior to
             Visit 1. The pharmacotherapeutic regimen was to remain stable during the conduct of
             the study.

          -  Had a history of learning disabilities or intellectual impairment that, in the opinion
             of the Investigator, would prevent the subject from participating in the study.

          -  Had impaired hepatic function (cirrhosis, hepatitis), glaucoma, or any symptomatic
             infection, any clinically significant hematologic, renal, endocrine, or
             gastrointestinal disease, and/or current neuropsychiatric condition with or without
             drug therapy, that was judged by the Investigator to be clinically significant and/or
             affect the subject's ability to participate in the clinical trial.

          -  Had a history of malignancy (except basal cell carcinoma), epilepsy or seizures
             (excluding febrile seizures), excessive alcohol intake or drug addiction,
             hypertension, or other clinically significant cardiovascular disease.

          -  Had a physical examination abnormality considered by the Investigator to be clinically
             significant and limiting to the study's conduct, unless the abnormality was related to
             underlying allergic rhinitis.

          -  Had a history of an allergy or hypersensitivity to cetirizine, loratadine,
             hydroxyzine, or any of their ingredients.

          -  Had asthma, which required any of the following within the past 30 days: 1) admission
             to the hospital, 2) emergency room visit, or 3) a change in dosing regimen. Subjects
             were allowed to continue theophylline, long acting β2 agonists, inhaled cromoglycate
             no more than 6.4 mg/day, or nedocrimil no more than 14 mg/day. Subjects were allowed
             to continue inhaled corticosteroids in doses not exceeding those listed in Appendix B
             of the study protocol, as long as the dose did not change during the study. Subjects
             were allowed the use of short acting β2 agonists on an as needed (PRN) basis.

          -  Had used intranasal or intra ophthalmic corticosteroids; oral leukotriene modifiers or
             leukotriene receptor antagonists within 14 days; or systemic (intramuscular and/or
             intravenous and/or oral) corticosteroids within 35 days prior to Visit 2. Topical
             corticosteroids for skin were allowed if covering ≤10% of body surface without
             occlusion.

          -  Used intranasal cromolyn (Nasalcrom®), optical cromolyn (Crolom®), ipratropium bromide
             (Atrovent® Nasal Spray), azelastine hydrochloride (Astelin® Nasal Spray), monamine
             oxidase (MAO) inhibitors, or beta blockers for the treatment of migraine headaches
             within 14 days prior to Visit 2.

          -  Used antiallergic ophthalmic treatments such as Acular®, Patanol®, or Alomide® within
             7 days prior to Visit 2.

          -  Used H1-receptor antagonists (oral and topical), H2-receptor antagonists, or
             decongestants after Visit 1.

          -  Used tricyclic antidepressants, tranquilizers, or antiemetics of the phenothiazine
             class within 14 days prior to Visit 2.

          -  Used oral macrolide antibiotics or oral antifungals within 7 days prior to Visit 2.

          -  Used saline nasal spray or ocular drops (unless for contact lens use) within 72 hours
             prior to Visit 2.

          -  Participated in any other studies involving investigational or marketed products
             within 30 days prior to entry into the study or participated in studies which involved
             norastemizole, or monoclonal anti-immunoglobulin E (IgE) antibody within 90 days prior
             to entry into the study.

          -  Donated blood or blood products for transfusion within 30 days prior to initiation of
             treatment with study drug and at any time during the study.
      

Gender

All

Ages

6 Years - 11 Years

Accepts Healthy Volunteers

No

Contacts

Dial Hewlett, MD, , 



Administrative Informations


NCT ID

NCT02932774

Organization ID

A1431009


Responsible Party

Sponsor

Study Sponsor

Johnson & Johnson Consumer and Personal Products Worldwide

Collaborators

 Pfizer

Study Sponsor

Dial Hewlett, MD, Study Director, Medical Director; Pfizer, Inc.


Verification Date

April 2017