Study of levocetirizine in seasonal allergic rhinitis

Abstract

Objective:

To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis (SAR) symptoms in US adults.

Research design and methods:

This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US. After a single-blind placebo run-in period, subjects received levocetirizine 5 mg or placebo once daily over 14 days.

ClinicalTrials.gov registry no.:

Trial registration: ClinicalTrials.gov identifier: NCT00621959.

Main outcome measures:

Primary efficacy variable was the Total 5-Symptom Score (T5SS). Secondary variables included Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Work Productivity and Activity Impairment–Allergy Specific (WPAI-AS) questionnaire, and Epworth Sleepiness Scale (ESS). Safety assessments were based on adverse events (AEs).

Results:

The intent-to-treat population comprised 596 subjects (levocetirizine, n = 301; placebo, n = 295). Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference (levocetirizine, 8.90 ± 0.19; placebo, 9.04 ± 0.19; adjusted mean difference, −0.14; p = 0.546). Levocetirizine showed numerical (mean RQLQ, WPAI-AS, ESS) and statistically superior differences (two domains within WPAI-AS) compared with placebo upon analysis of secondary efficacy variables. The incidence of treatment-emergent AEs was similar (levocetirizine, 23.9%; placebo, 24.4%). As the lack of efficacy was inconsistent with all previous levocetirizine studies, post hoc analyses were performed to assess the influence of pollen counts, geography, and other factors; however, no conclusive explanation could be identified.

Conclusions:

In this study, levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR. This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run, similarly designed US study. It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies, irrespective of the methodologic quality.

Key words::

• Allergic rhinitis, seasonal
• Antihistamines
• Levocetirizine
• Randomized controlled trial
• Treatment efficacy

Transparency

Declaration of funding

This research was funded by UCB, Inc. and sanofi-aventis U.S. LLC.

Declaration of financial/other relationships

L.E.M. has disclosed that he has received research grants from AstraZeneca, GlaxoSmithKline, and several other pharmaceutical companies. He also is on the speakers bureau of several pharmaceutical companies. F.H. has disclosed that he is a clinical investigator for sanofi-aventis. L.E.M. and F.H. have disclosed that they received no honoraria or other forms of financial support related to the development of this manuscript. G.G. has disclosed that he is an employee of sanofi-aventis. J.C.H. has disclosed that he is an employee of UCB.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors thank John F. Kincaid, MD, and Peloton Advantage for their editorial assistance in preparing this manuscript, which was funded by sanofi-aventis and UCB.

The authors were fully responsible for all content, editorial decisions, and opinions expressed in this paper.

Notes

*Xyzal, UCB, Inc., Smyrna, Ga, and sanofi-aventis U.S. LLC, Bridgewater, NJ, USA.