Levocetirizine for Allergic Asthma

(HAS3 Trial)

Overseen By Darlene Brenson-Hughes, CCRC

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Children's Mercy Hospital Kansas City

Must be taking: Asthma therapy

Must not be taking: Tricyclic antidepressants

Disqualifiers: Pregnancy, Chronic lung disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 6 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate how well Levocetirizine, an allergy medication, controls asthma in children with persistent allergic asthma. It focuses on African American/Black and Caucasian/White children with various asthma reactions. Participants will receive either Levocetirizine or a placebo (a treatment that mimics the real one) alongside their usual asthma care. Children aged 6 to 17 with uncontrolled asthma, a known allergy, and who identify as African American/Black or Caucasian/White may qualify for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in asthma treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking medications that affect histamine response. If you are currently on or have been on Tricyclic Antidepressants in the past 30 days, you cannot participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that levocetirizine is generally safe and effective for treating allergy symptoms. In past studies, 14.4% of people taking levocetirizine experienced side effects, compared to 18.4% of those taking a placebo (a pill with no active medicine). Common mild side effects included sleepiness and tiredness, affecting less than 1% of users.

The FDA has approved levocetirizine for treating allergies in both children and adults, indicating it is considered safe for these uses. However, always consult a healthcare professional before starting any new treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Unlike standard treatments for allergic asthma, which often include inhaled corticosteroids and long-acting beta agonists, Levocetirizine is an oral antihistamine. Researchers are excited about Levocetirizine because it targets histamine receptors to reduce allergic reactions, potentially offering relief with fewer side effects and simpler administration. This could make managing allergic asthma more convenient, especially for those who struggle with inhaler use. Additionally, Levocetirizine's quick action could provide faster symptom relief compared to some existing therapies, making it an attractive option for both patients and healthcare providers.

What evidence suggests that Levocetirizine might be an effective treatment for allergic asthma?

Research shows that Levocetirizine, which participants in this trial may receive, effectively manages symptoms of allergic asthma. Previous studies have demonstrated its ability to improve the quality of life for people with allergies. It controls asthma symptoms by reducing swelling and provides 24-hour relief. Studies have also found that it improves symptoms like a runny or stuffy nose and enhances the quality of life for those with asthma, while remaining safe for long-term use. Overall, evidence supports Levocetirizine as a promising treatment for managing ongoing allergic asthma. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for African American/Black and Caucasian/White children aged 6-17 with uncontrolled persistent allergic asthma, who are already on asthma treatments. They must not have significant liver, kidney, or immune diseases, be pregnant, or unable to follow the study procedures.

Inclusion Criteria

I am a child who identifies as African American/black or Caucasian/white, including my parents and grandparents.

My asthma is not well-controlled, as shown by my recent ACT score.

You have shown allergic reactions in a skin or blood test.

Exclusion Criteria

I have a chronic lung condition other than asthma.

I have taken Tricyclic Antidepressants in the last 30 days.

I do not have chronic liver, kidney, immune, blood, or cancer conditions as decided by the study leader.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline/Pre-dose

Baseline assessments including asthma control and quality of life measures are conducted before randomization

1 week

1 visit (in-person)

Treatment

Participants receive Levocetirizine or placebo for 6 weeks, with assessments of asthma control and quality of life

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including asthma control and quality of life assessments

6 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Levocetirizine Dihydrochloride
• Placebo

Trial Overview The HAS3 trial is testing Levocetirizine (an antihistamine) against a placebo in controlling asthma symptoms. Children will be randomly assigned to receive either the medication or placebo in a blinded manner where neither they nor the researchers know which one they're getting.

How Is the Trial Designed?

Group I: Levocetirizine (LTZ) Active Control 1 Intervention

Participants will take Levocetirizine dihydrochloride/ Xyzal® (UCB, Inc.) immediate release oral solution 2.5mg/5ml (2.5mg in children 6-11 years of age; 5mg in children \>11 years per recommended doses) in addition to their current asthma regimen.

Group II: Placebo Placebo Group 1 Intervention

Participants will take a placebo solution previously developed by the Children's Mercy Investigational Pharmacy to match the color, flavor, and consistency of the active drug in addition to their current asthma regimen.

Levocetirizine Dihydrochloride is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xyzal for:

• Allergic Rhinitis
• Urticaria

Approved in European Union as Levocetirizine for:

• Allergic Rhinitis
• Urticaria
• Chronic Idiopathic Urticaria

Approved in Canada as Levocetirizine for:

• Allergic Rhinitis
• Urticaria

Approved in Japan as Levocetirizine for:

• Allergic Rhinitis
• Urticaria

Who Is Running the Clinical Trial?

Children's Mercy Hospital Kansas City

Lead Sponsor

Trials

261

Recruited

941,000+

Bridgette Jones

Lead Sponsor

Trials

1

Recruited

300+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

Levocetirizine is classified as a BCS Class 1 drug, indicating it has high solubility and permeability, which supports its effectiveness in treating skin rashes and allergic rhinitis.

The study suggests that a BCS-based biowaiver can be applied for levocetirizine products, allowing for bioequivalence assessments without human pharmacokinetic studies, provided certain conditions regarding excipients and dissolution testing are met.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Levocetirizine Dihydrochloride. Charoo, NA., Abdallah, DB., Ahmed, DT., et al.[2023]

Levocetirizine, when complexed with β-cyclodextrin, results in rapidly disintegrating tablets that significantly improve the drug's solubility and release profile, with 99.99% of the drug released within 10 minutes.

The tablets demonstrated a fast disintegration time of 15-35 seconds, with the best batch achieving a minimum disintegration time of 20 seconds, indicating potential for quick relief in allergic rhinitis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation and characterization of oral rapid disintegrating tablets of levocetirizine. Samvedna, S., Jindal, S., Mishra, G., et al.[2019]

The novel flexible vesicle (FV) formulation of levocetirizine demonstrated a 1.78-fold increase in skin permeation compared to conventional formulations, enhancing its potential effectiveness for treating allergies.

In an animal model of atopic dermatitis, the FV formulation significantly reduced scratching and erythema scores, indicating improved therapeutic efficacy while also being safe and non-toxic for dermal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel flexible vesicles based topical formulation of levocetirizine: in vivo evaluation using oxazolone-induced atopic dermatitis in murine model. Goindi, S., Kumar, G., Kaur, A.[2014]

Levocetirizine, a second-generation antihistamine, has been shown to significantly improve nasal symptoms in patients with persistent allergic rhinitis (PER) as early as the first week of treatment, based on a study involving 551 participants.

This medication not only enhances the quality of life for patients but also offers economic benefits by reducing costs for employers and society, making it a highly effective treatment option for managing allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of persistent allergic rhinitis: evidence-based treatment with levocetirizine. Mullol, J., Bachert, C., Bousquet, J.[2021]

Levocetirizine is an effective and well-tolerated treatment for allergic rhinitis and chronic idiopathic urticaria, showing better efficacy than other antihistamines like desloratadine and loratadine in allergen challenge studies.

It has a rapid onset, long-lasting effects, and minimal side effects, including no impact on cognition or cardiovascular function, making it a valuable option among newer antihistamines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levocetirizine: a review of its use in the management of allergic rhinitis and skin allergies. Hair, PI., Scott, LJ.[2018]

A study involving 22 healthy male subjects found that the pharmacokinetic profiles of montelukast and levocetirizine were equivalent whether administered separately or as a fixed-dose combination, indicating that the combination tablet is a viable option for treatment.

The pharmacokinetic parameters, including maximum plasma concentration and area under the curve, met equivalence criteria, suggesting that patients can expect similar efficacy and safety from the combination tablet as from taking the medications individually.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative pharmacokinetics of a montelukast/levocetirizine fixed-dose combination chewable tablet versus individual administration of montelukast and levocetirizine after a single oral administration in healthy Korean male subjects . Moon, SJ., Yu, KS., Jung, J., et al.[2021]

Levocetirizine hydrochloride granules (Kangzhitai®) demonstrated bioequivalence to the reference drug Xyzal® in a study involving 20 healthy male subjects, indicating similar absorption and pharmacokinetic profiles.

Both drugs showed no significant differences in key pharmacokinetic parameters such as Cmax and AUC, and no adverse events were reported, highlighting the safety of Kangzhitai® as an effective antihistamine for treating allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of Levocetirizine Hydrochloride Granules (Kangzhitai) in Healthy Subjects. Xiang, H., Yang, G., Tan, H.[2023]

In a 6-month study involving 551 adults with persistent allergic rhinitis, levocetirizine significantly improved quality of life and allergy symptoms compared to placebo, with results showing benefits as early as one week (P < 0.001).

The treatment not only enhanced symptom relief but also reduced overall disease-related costs for patients, indicating its efficacy in managing allergic rhinitis effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent Allergic Rhinitis and the XPERT Study. Rogkakou, A., Villa, E., Garelli, V., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16961716/

Levocetirizine in persistent allergic rhinitis and asthma Conclusions LCZ is clinically effective and capable of improving the rhinitis-asthma-related QoL. Publication types. Randomized Controlled Trial; Research ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15480324/

Levocetirizine improves quality of life and reduces costs in ... Conclusion: Levocetirizine was shown to improve quality of life and symptoms and to decrease the overall costs of the disease over the 6-month treatment period.

3. allergyimmunoljournal.com allergyimmunoljournal.com/articles/aaai-aid1031.php

Effectiveness of levocetirizine in treating allergic rhinitis ... Results demonstrated that evening administration of Levocetirizine facilitates 24-hour symptom control while having no significant effect on daytime somnolence.

4. aacijournal.biomedcentral.com aacijournal.biomedcentral.com/articles/10.1186/1710-1492-5-14

The anti-inflammatory effects of levocetirizine A more recent randomized double-blind study reported positive effects by 5 mg levocetirizine given daily over eight weeks compared with placebo ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/022064s009lbl.pdf

XYZAL (levocetirizine dihydrochloride) Label The long-term (exposure of 4 or 6 months) safety data are based upon two clinical trials in adults and adolescents in which 428 patients (190 males and 238 ...

6. webmd.com webmd.com/drugs/2/drug-148989/levocetirizine-oral/details

Levocetirizine (Xyzal) - Uses, Side Effects, and More Levocetirizine is an antihistamine that is taken to help treat allergy symptoms, such as a runny nose, itchy or watery eyes, sneezing, or an itchy nose or ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20377116/

Efficacy and safety of levocetirizine in improving symptoms ... Overall incidence of treatment-emergent adverse events was 14.4% for levocetirizine and 18.4% for placebo. The incidence of somnolence and fatigue was 0.7% and ...

8. reference.medscape.com reference.medscape.com/drug/xyzal-levocetirizine-343385

Xyzal (levocetirizine) dosing, indications, interactions, ... Indicated for relief of symptoms associated with seasonal and perennial allergic rhinitis. 5 mg PO qDay in evening. Some patients may respond to 2.5 mg/day.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00619801

Safety Study of Levocetirizine Dihydrochloride Oral Liquid ... 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 ...