study of Fixed Dose combination of Levocetrizine Hydrochloride 5 mg and Montelukast 10mg in patients with Seasonal Allergic Rhinitis
- Conditions
- Diseases of the respiratory system,
- Registration Number
- CTRI/2020/08/027125
- Lead Sponsor
- Fourrts India Laboratories Pvt Ltd
- Brief Summary
Seasonal Allergic Rhinitis
Allergic rhinitis is the most common atopic disorder affecting 18% to 40% of adults worldwide, diagnosed by history, physical exam and objective testing [1]. According to the Allergic Rhinitis and its Impact on Asthma (ARIA) document it is classified by chronicity (intermittent or persistent), and severity which is based on symptoms and quality of life (mild, or moderate/ severe). The terms “seasonal†and “perennial†allergic rhinitis were previously categorized as allergic rhinitis by the clinically significant aeroallergen. Seasonal allergic rhinitis (SAR) is commonly referred to as “hay feverâ€, developing during a defined pollen season, and is usually intermittent, as a result of allergic reactions to outdoor aeroallergens including mould spores, and pollens of trees, grasses, and weeds that depend on wind for cross-pollination. It is characterized by symptoms like sneezing, itching, rhinorrhoea and nasal obstruction. Allergic rhinitis is often associated with ocular symptoms. Allergic rhinitis affects 10–30% of adults and up to 40% of children. It is a global health problem causing major illness and disability. It has wide adverse impact on the patient in different aspects like affecting social life, school, work and sleep [2].
Drug therapy for allergic rhinitis should be guided by the type and severity of individual patient’s symptoms and should reduce nasal congestion, sneezing, and rhinorrhea over the course of the entire day and night and physician preferences [3,5]. Pharmacotherapy includes oral and intranasal H1 antihistamines, intranasal corticosteroids, oral and intranasal decongestants, intranasal anticholinergics, intranasal cromolyn and leukotriene receptor antagonists
Antihistamines and Antileukotriene
Histamine is one of the key mediators released from mast cells and basophils which play a major role in the pathophysiology of rhinitis. H1 antihistamines are the first-line medicines for the treatment of allergic rhino- conjunctivitis. When selecting an oral H antihistamine, it is important to consider the clinical efficacy and balance it against the risk of adverse effects of an antihistamine. First- generation H -antihistamines have detrimental effects on sleep and learning. Allergic diseases are also known to impair the functions. The detrimental effects caused by first generation H1 antihistamines may be exacerbated by the allergic diseases. Second generation antihistamines have shown favourable effect on sleep in patients with allergic rhinitis [5,6,7] and are in general recommended for mild to moderate disease as first-line therapy, but not effective in nasal congestion. Newer antihistamines provide similar efficacy as first-generation antihistamines but with less sedation [2].
Levocetirizine, the R-enantiomer of cetirizine, is a potent and selective antagonist of peripheral H1-receptors. It has been demonstrated by recent studies that the treatment of allergic rhinitis (AR) with concomitant administration of an antileukotriene (montelukast) and an antihistamine (levocetirizine), shows significantly better symptom relief compared with the modest improvement of rhinitis symptomatology with each of the treatments alone. Levocetirizine 5 mg/day was effective in reducing symptoms of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis and improving quality of life, with an acceptable tolerability profile.
Montelukast sodium is an orally active compound that binds with high affinity and selectivity to the CysLT type-1 (CysLT1) receptor. Montelukast inhibits physiologic actions of LTD4 at the CysLT1 receptor without any agonist activity. It therefore acts as a leukotriene receptor antagonist. It is effective in improving daytime and night-time symptoms of allergic rhinitis. It also serves a role in helping reduce symptoms of allergic rhinitis that are not controlled with antihistamines alone by competitively and reversibly inhibits cysteinyl leukotrienes (CysLTs), specifically leukotrienes D4 (LTD4), theoretically decreasing congestion and stuffiness associated with allergic rhinitis [4]. Montelukast, as monotherapy has been effective in improving daytime and night time symptoms in patients with allergic rhinitis [2, 8] and in comparison to antihistamines appear to have significantly better improvement in night time symptoms [9-11].
Hence, a combination therapy of montelukast with antihistamines could provide enhancing and complementary effects, thereby reducing both the daytime and night time symptoms effectively. Fixed dose combination of levocetirizine 5 mg with montelukast 10mg has shown a significant improvement in patients with SAR. The combination was found to be well tolerated in many studies. There was a significant improvement in both daytime and night time symptoms in patients on combination therapy as compared to placebo and giving both the drugs as monotherapy [12-15]. There are only limited studies available for the effect of combination therapy of montelukast and levocetirizine on the Indian population.
Purpose of Study
This is an open label, post-marketing study to evaluate safety on administration of fixed dose combination (FDC) of Levocetirizine Hydrochloride 5 mg and Montelukast 10 mg in patients with seasonal allergic rhinitis. The total study duration will be approximately 13 weeks. Approximately 200 male or female patients are planned to be enrolled in 4 centers in India. For each enrolled subject, there will be a 1-day Screening & Baseline visit on Day 1 (Visit 1), Week 2 (Visit 2 – Telephonic Vist), Week 4 (Visit 3 – Telephonic Visit), Week 8 (Visit 4 – Clinic Visit) and followed by a follow-up period until End of study Visit (Week 13 – Telephonic Visit). Prior to the day of Screening/Baseline, study eligibility according to the inclusion and exclusion criteria will be confirmed. On the Day of Screening & Baseline, the medical history of all the subjects will be reviewed. All subjects will be prescribed Levocetirizine Hydrochloride 5 mg and Montelukast 10 mg once a day, orally at Baseline (Visit 1) before bedtime for 8 weeks. During the treatment period, the scheduled visits are (Visits 2, 3, 4) for efficacy, safety and tolerability assessment. The subjects are followed up by the investigator for any signs and symptoms along with adverse events (AEs) until EOS (Week 13). Subject data will be collected during the study duration at the clinic visits. The medical compliance was determined from the returned tablet count. A physical examination for nasal secretion and turbinate swelling was also done at each clinic visit. Data in a routine clinical monitoring of subjects are collected in the paper case report form (CRF).
Daily rhinitis diary card Recorded on the daily diary card, the allergic rhinitis and conjunctivitis symptoms are assessed on a 4-point scale (0 to 3) for both daytime (diary card completed in the evening) and night time (diary card completed on awakening). The daytime nasal (rhinorrhea sneezing, itching, and congestion), night time nasal (nasal congestion upon awakening, difficulty going to sleep, and night time awakening) and eye (tearing, itching, redness and puffing) symptoms and their rating are described to every patient by the same technician. The ratings of the symptom are: 0 = not noticeable, 1 = mild symptoms, 2 = moderate symptoms, 3 = severe symptoms. The rating had to be performed by the patients themselves to increase the creditability of the subjective scale.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- All
- Target Recruitment
- 200
- Willing and able to sign informed consent form.
- Written informed consent must be obtained before any assessment is performed • Patients with history of SAR prior to the study • Patients who agree to maintain consistency in their surroundings throughout the study period.
- • Were patients from outpatient department of ENT and general physician between the age group of 18–65 years of either gender having moderate-severe intermittent or mild persistent AR according to original ARIA classification.
- • The study inclusion criteria required the patients with total nasal symptom score (TNSS) of 5 or higher, not treated with antihistaminics in the previous week.
- Hypersensitivity to Levocetirizine Hydrochloride 5 mg and Montelukast 10 mg or any excipients • Patients with upper respiratory tract infection or acute/chronic pulmonary disorder • Patients also with non-allergic rhinitis with different causes.
- • Patients with severe asthma.
- • Presence of nasal polyps or any clinically important nasal anomaly.
- • History of acute/chronic sinusitis within 30 days of Visit 1 • History of intranasal / eye surgeries within 3 months of Visit 1 • Initiation of immunotherapy or dose modification within 1 month prior to Visit 1 • Have presence of any condition that in the opinion of the physician places the patient at undue risk or potentially jeopardizes the quality of data to be generated.
- • Patient requiring other anti- histamine, corticosteroids (oral and/parenteral), immunotherapy, cromolyn sodium, nedocromil and inhaled cholinergics, oral or long acting beta-agonist, theophylline, tricyclic antidepressants, other leukotriene modifiers and bronchodilators, etc that may affect the efficacy of study drug are not enrolled in the study.
- • Decongestants, anti-inflammatory medicines and other rescue medicines for allergic rhinitis are not permitted during the study.
- • Should not be suffering from any other psychiatric illness or any other chronic disease which would interfere with trial assessments.
- • Known contraindication for the use of Levocetirizine Hydrochloride and Montelukast • A history of drug or alcohol abuse within the past 6 months • Currently participating (or participated within the previous 30 days) in an investigational therapeutic or device study • Female who is pregnant, nursing, or of child-bearing potential.
Study & Design
- Study Type
- PMS
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To collect and assess safety of fixed dose combination of levocetirizine 5mg + montelukast 10mg in patients with seasonal allergic rhinitis To monitor adverse events (AEs)/adverse drug reaction (ADR), serious adverse events (SAEs)/ serious adverse drug reactions (SADRs), unexpected AE/ADR and unexpected SAE/SADR
- Secondary Outcome Measures
Name Time Method Efficacy will be evaluated as change in day time nasal symptom score (average of scores of nasal congestion, rhinorrhea, itching and sneezing Efficacy from baseline to end of the treatment
Trial Locations
- Locations (4)
Health Point Hospital
🇮🇳Kolkata, WEST BENGAL, India
Mahatma Gandhi Medical College & Research Institute,
🇮🇳Pondicherry, PONDICHERRY, India
Medstar Speciality Hospital
🇮🇳Bangalore, KARNATAKA, India
Udyaan Health care
🇮🇳Lucknow, UTTAR PRADESH, India
Health Point Hospital🇮🇳Kolkata, WEST BENGAL, IndiaDr Sarmishtha BandyopadhyayPrincipal investigator8420011311anant@indorivclinical.com