Comparative Study of Bilastine, Ebastine, and Desloratadine on Histamine-Induced Wheal and Flare Suppression in Healthy Volunteers
- Trial ID
- 2024-516569-35-00
- Sponsor
- Faes Farma S.A.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine the **onset of action** of the peripheral antihistaminic activity of bilastine 20 mg orodispersible tablet, ebastine 10 mg oral lyophilized, and desloratadine 5 mg orodispersible tablet compared to a placebo orodispersible tablet. This is clinically relevant as it provides insights into the rapidity with which these antihistamines can begin to alleviate allergic symptoms, which is crucial for managing acute allergic reactions effectively.
Secondary objectives include:
- Evaluating the peripheral antihistaminic activity at each time point of the different study drugs versus placebo and their corresponding baseline values, measured as the percentage of inhibition of wheal and flare areas.
- Determining the maximum effect, maximum effect time, and duration of effect of the treatments.
- Evaluating the suppression of subjective sensation of itching after histamine inoculation.
- Assessing the safety and tolerability of the treatments.
- Characterizing the pharmacokinetic profile of bilastine 20 mg orodispersible tablets.
Participants
The clinical trial focuses on evaluating the onset of action of the peripheral **antihistaminic** activity of bilastine, ebastine, and desloratadine in individuals with **allergy**. The study population comprises both male and female participants aged between 18 and 50 years. Participants are required to be in good general health, with no significant abnormalities in medical records, physical examinations, or laboratory assessments, including haematology, biochemistry, and serology. Vital signs and electrocardiogram results must be within normal ranges. The body mass index (BMI) of participants should be between 18.5 and 30.0 kg/m². Women of childbearing potential are required to use a medically acceptable barrier method of contraception throughout the study. Participants must avoid excessive sun exposure and any procedures that could alter skin color. The trial includes a vulnerable population, but the total number of participants is not provided by the sponsor.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, crossover study to evaluate the efficacy of orodispersible presentations of **bilastine**, **ebastine**, and **desloratadine** in suppressing wheal and flare reactions induced by intradermal histamine in healthy volunteers. The primary objective is to determine the onset of action of these antihistaminic agents compared to a placebo. The trial is expected to commence on April 1, 2025, with an estimated completion date of June 2, 2025.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, including age, health status, and willingness to comply with study requirements. The inclusion criteria require participants to be between 18 and 50 years old, free from significant medical conditions, and to have normal vital signs and laboratory results. Women of childbearing potential must agree to use a barrier method of contraception. The screening visit will also include a histamine skin reaction test to ensure induced wheal area values fall within the reference range.
Following successful screening, participants will be randomized to receive single doses of the study drugs or placebo in a crossover manner. Each treatment period will be separated by a washout phase to prevent carryover effects. The study will include follow-up visits to monitor the primary endpoint, which is the onset of action, defined as the first time point where active treatments show a statistically significant difference in wheal and flare inhibition compared to placebo. Secondary endpoints include the percentage of reduction in wheal and flare areas, maximum effect, duration of effect, subjective itching assessment, tolerability, safety, and pharmacokinetic parameters.
The expected length of participant involvement is approximately two months, considering the crossover design and washout periods. Conditions that may lead to early termination from the study include the occurrence of adverse events, non-compliance with study procedures, or withdrawal of consent. The end-of-study visit will involve a final assessment of safety and efficacy parameters, ensuring the well-being of participants before study completion.
Treatment
The clinical trial involves the administration of **Desloratadine** 5 mg orodispersible tablets, which are formulated for oral administration. The active substance, desloratadine, is a chemical compound classified under the ATC code R06AX27. The tablets are manufactured by Bristol Laboratories Limited and are designed to dissolve in the mouth, facilitating ease of administration. The maximum daily dose is 5 mg, with a treatment period limited to one day. Participants are required to take the medication orally once during the trial period.
Another experimental treatment in the trial is **Ebastine** 10 mg oral lyophilisate, marketed as Bactil Flas. This formulation is also intended for oral use and is produced by Laboratorios Almirall, S.L. Ebastine is categorized under the ATC code R06AX22. The maximum daily dose is 10 mg, and the treatment duration is restricted to one day. The oral lyophilisate is designed to dissolve quickly in the mouth, ensuring rapid absorption and onset of action.
The trial also includes **Bilastine** 20 mg orodispersible tablets, known commercially as Bilaxten. These tablets are produced by FAES FARMA, S.A. and are intended for oral use. Bilastine is classified under the ATC code R06AX29. The maximum daily dose is 20 mg, with a total allowable dose of 40 mg over a two-day treatment period. The orodispersible formulation allows for convenient administration without the need for water.
A **Placebo** orodispersible tablet is used as a comparator in this double-blind, placebo-controlled trial. The placebo is designed to mimic the appearance and administration route of the active treatments, ensuring blinding of both participants and investigators. The placebo is administered orally, following the same dosing schedule as the active treatments, to maintain consistency across the study arms.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the **onset of action**, defined as the first time point at which active treatments show a statistically significant difference in the inhibition of wheal and flare surface areas compared to placebo. This will be measured by evaluating the surface areas of wheal and flare induced by intradermal histamine in healthy volunteers.
Secondary endpoints include the percentage of reduction in wheal and flare surface areas versus placebo and baseline, the maximum effect and its corresponding time point, and the duration of effect. Additionally, subjective itching assessment will be conducted using a visual analog scale (VAS) to determine mean changes from baseline. Tolerability will be evaluated through clinical laboratory tests, vital signs, and ECG parameters, while safety will be assessed by monitoring the incidence of adverse events. Pharmacokinetic parameters, including drug plasma concentration and various pharmacokinetic metrics (AUC0t, AUC0∞, Cmax, tmax, t1/2, Kel, Cl, Vd), will also be calculated from plasma levels.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Free acceptance to participate in the study by obtaining signed informed consent form, approved by the hospital’s IEC.
- Subjects of either sex (male or female) aged ≥ 18 and ≤ 50 years at the time of the enrolment.
- Subjects not affected by any organic or psychic conditions.
- No evidence of clinically significant abnormalities in medical records and physical examination, at screening.
- No clinically significant abnormalities in haematology, biochemistry, or serology (hepatitis B surface antigen - HBsAg, hepatitis C antibodies – HCV Ab, or human immunodeficiency virus antibodies - HIV) assessments, at screening.
- Vital signs (blood pressure, body temperature and heart rate) and electrocardiogram (ECG) record within normal range, at screening.
- Body mass index within the range (BMI ≥ 18.5 and ≤ 30.0 kg/m2) expressed as weight (kg) / height (m2).
- Women of childbearing potential must be willing to use a medically acceptable barrier method of contraception throughout the study and one week after the last IMP intake. Hormonal contraceptives and intrauterine hormone-releasing system (IUS) are not permitted.
- Induced wheal area values within the reference range of the Research Institute [0.5521 cm2 – 2.5941 cm2], in the histamine skin reaction test performed during the selection.
- Be willing to avoid excessive sun exposure or any procedure that could modify the colour of the skin.
Exclusion Criteria
- Background of allergy, idiosyncrasy or hypersensitivity to the IMP or any related products (including excipients of the formulations).
- Heavy consumer of stimulating drinks (> 5 cups of coffee, tea, chocolate, or cola drinks per day).
- History of alcohol dependence or drug abuse in the last 5 years, or daily alcohol consumption > 40 g/day for men or > 24 g/day for women.
- Intake of any medication within 14 days prior to taking the IMP (except for use of paracetamol in short-term symptomatic treatments, according to the investigator’s criteria, and specified contraceptives), or intake of over-the-counter products (including natural food supplements, vitamins and medicinal plant products) within 7 days prior to taking the IMP.
- Positive HBsAg, HCV Ab or HIV results.
- Positive results for abuse drugs in urine test or ethanol in breath test.
- History or clinical evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, haematological, neurological disease or other chronic diseases.
- Rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
- Positive dermographism.
- Females with positive results from the pregnancy test, breast-feeding or planning a pregnancy.
- Smoking within 6 months prior to the study treatment phase. Smokers must refrain from any tobacco usage, including smokeless tobacco, nicotine patches, electronic cigarettes, etc. at least for 6 months prior to study treatment phase).
- Have participated in another clinical trial during the 3 months prior to study start (screening visit) in which an investigational drug, medical device or a commercially available drug was tested.
- Have donated blood within the 4 weeks period before the screening visit.
- Having undergone major surgery during the previous 6 months before screening visit, or have an intervention programmed during the study.
- Mentally or legally incapacitated at screening.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Any condition that, in the opinion of the investigator, may jeopardise the subject’s well-being or the trial conduct according to the protocol.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 01 Apr 2025 | 26 |
Sites & Investigators
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo | Placebo | N/A | — | — | — | N/A |
Desloratadine 5 mg orodispersible tablets | Test | ORODISPERSIBLE TABLETS | ORAL | 5 | 1 | PRD3973579 |
Bactil Flas 10 mg Liofilizados orales | Test | LIOFILIZADOS ORALES | ORAL | 10 | 1 | PRD6250413 |
Bilaxten 20 mg comprimidos bucodispersables | Test | COMPRIMIDOS BUCODISPERSABLES | ORAL USE | 20 | 2 | PRD10273993 |