Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO

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.