title: A randomized, comparative, multicentric clinical trial to assess the efficacy and safety of zileuton extended-release tablets with montelukast sodium tablets in patients suffering from chronic persistent asthma.
abstract: Leukotriene (LT) modifiers are anti-inflammatory drugs that are useful as an add-on therapy with first-line asthma-controller medications. This group includes LT synthesis inhibitors (eg, Zileuton) and receptor antagonists (eg, Montelukast), whose direct comparative clinical data are not available. This study was conducted to assess the comparative efficacy and safety of orally administered Zileuton extended-release (ER) with Montelukast sodium in patients suffering from chronic persistent asthma. Patients of 18-65 years of age with mild to moderate chronic stable asthma were randomized to treatment with Zileuton ER 2400 mg/d or Montelukast 10 mg/d for 12 weeks. Peak expiratory flow rate (PEFR) and asthma symptoms (cough, wheeze, chest tightness, and shortness of breath each on a 4-point scale) were assessed on monthly scheduled out-patient visits. Safety assessments by clinical and laboratory parameters were carried out during the course of the study. Among 210 patients eligible for efficacy assessment, PEFR improved by 64.8 ± 52.8 (95% confidence interval: 54.8-74.7) L/min with Zileuton ER (n = 109) and 40.6 ± 47.5 (31.3-49.9) L/min with Montelukast (n = 101; P < 0.001), whereas percent improvements were 27.0% (22.6%-31.5%) versus 18.4% (14.1%-22.7%), respectively (P = 0.006). Zileuton ER lead to ≥12% PEFR improvements in 74 of 109 [67.9% (59.1%-76.7%)] patients, whereas the same was noted in 52 of 101 [51.5% (41.7%-61.2%)] patients receiving Montelukast (P = 0.015). The reduction in the mean overall symptom intensity score was also significantly better with Zileuton ER [-5.0 ± 2.1 (4.6-5.4) versus -4.2 ± 2.3 (3.8-4.7)] (P = 0.018); however, the same was not observed for the decline in the individual symptom scores. A lesser but not significantly different adverse event rate was reported in the Zileuton ER group than the Montelukast group with the commonest events being headache and gastrointestinal effects in both the groups. Thus, Zileuton ER seems to be more efficacious than Montelukast and well tolerated for the treatment of mild to moderate chronic persistent asthma in adult patient population. Further studies can elucidate the comparative treatment benefits of these LT modifiers in asthma management.
authors.affiliation: Clinical Research and Regulatory Affairs Department, Cadila Healthcare Ltd, Ahmedabad, India. amitkubavat@zyduscadila.com
authors.forename: Amit H
authors.initials: AH
authors.lastname: Kubavat
authors.forename: Narendra
authors.initials: N
authors.lastname: Khippal
authors.forename: Sandeep
authors.initials: S
authors.lastname: Tak
authors.forename: Puneet
authors.initials: P
authors.lastname: Rijhwani
authors.forename: Salil
authors.initials: S
authors.lastname: Bhargava
authors.forename: Tushar
authors.initials: T
authors.lastname: Patel
authors.forename: Nalin
authors.initials: N
authors.lastname: Shah
authors.forename: Rakeshkumar R
authors.initials: RR
authors.lastname: Kshatriya
authors.forename: Ravindra
authors.initials: R
authors.lastname: Mittal
mesh_terms: D000085:Acetates / Q000009:adverse effects / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002908:Chronic Disease; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013440:Sulfides; D013607:Tablets; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D013607:Tablets; C093875:montelukast; C063449:zileuton; D006918:Hydroxyurea