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

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled, crossover study comparing asthma control post treatment in African American/Black and Caucasian/White children in both hyper and hypo responsive HILD (Histamine Lontophoresis with Laser Doppler monitoring) phenotypes with uncontrolled persistent allergic asthma using Levocetirizine (LTZ) vs placebo.

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.

What evidence supports the effectiveness of the drug Levocetirizine for allergic asthma?

Levocetirizine has been shown to be effective in treating allergic rhinitis, which often coexists with asthma, by improving symptoms and quality of life in patients. This suggests it may also help manage allergic asthma symptoms, as both conditions share similar allergic pathways. ^{1 2 3 4 5}

Is Levocetirizine safe for humans?

Levocetirizine is generally well tolerated and considered safe for humans, with studies showing it has a low potential for drug interactions and does not affect cognition, psychomotor function, or the cardiovascular system. It is widely used for treating allergies and has a wide therapeutic index, meaning it is unlikely to cause severe side effects. ^{1 2 3 6 7}

How does the drug Levocetirizine differ from other treatments for allergic asthma?

Levocetirizine is a newer generation antihistamine that works by blocking H1 receptors to reduce allergy symptoms without causing drowsiness. It is known for its rapid onset, long-lasting effects, and low potential for drug interactions, making it a unique option compared to other antihistamines. ^{1 2 3 7 8}

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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, 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 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]

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, 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Persistent Allergic Rhinitis and the XPERT Study. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Levocetirizine: a review of its use in the management of allergic rhinitis and skin allergies. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Bioequivalence of Levocetirizine Hydrochloride Granules (Kangzhitai) in Healthy Subjects. [2023]

4. Germany 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 . [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Management of persistent allergic rhinitis: evidence-based treatment with levocetirizine. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Levocetirizine Dihydrochloride. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Novel flexible vesicles based topical formulation of levocetirizine: in vivo evaluation using oxazolone-induced atopic dermatitis in murine model. [2014]

8. Poland pubmed.ncbi.nlm.nih.gov

Formulation and characterization of oral rapid disintegrating tablets of levocetirizine. [2019]