Ipratropium bromide （IB） is an effective treatment for reversible bronchospasm associated with COPD. Cipla Ltd. hasdeveloped a formulation of lpratropium bromide pMDI （Test IB） which is designed to be equivalent t...Ipratropium bromide （IB） is an effective treatment for reversible bronchospasm associated with COPD. Cipla Ltd. hasdeveloped a formulation of lpratropium bromide pMDI （Test IB） which is designed to be equivalent to the originator product Atrovent HFA pMDI （Reference IB） as a cost effective alternative for the treatment of COPD. The objective of the study was to establishnon-inferiority of the Test 1B to Reference 1B in patients with stable COPD. In this multicenter, randomized, double-blind, doubledummy, parallel group study, patients aged 〉 40 years were randomized to receive 2 puffs three times daily （TID） of either the Test IBor Reference IB for 12 weeks. The primary endpoint was the change from pre dose to post dose FEVj at 90 min at the end of 12 weeks.Secondary endpoints included FVC, symptom score, rescue medication use and St. George＇s Respiratory Questionnaire （SGRQ）.Safety and tolerability included evaluation of adverse events （AEs）, vital signs assessments, physical examination and any change inconcomitant medications. A total of 395 patients were randomized to either the Test IB （n = 199） or the Reference IB （n = 196）; themajority of patients were male with a mean pre-bronchodilator FEV1 （% predicted） of 60%. The per protocol set comprised of 258patients （n = 129 in each treatment group）. The mean treatment difference between the Test IB and Reference 1B for the primaryendpoint （mean change in FEV1 from pre-dose to 90 rain post dose at 12 weeks） was -0.003 L and the lower limit of the 95% confidenceinterval （CI） for the difference between the two products was -0.041 Lwhich is greater than the predefined non inferiority limit of-0.100 L. No significant difference was seen between the Test IB and Reference IB for any secondary efficacy variables. The AEprofile was also comparable between the two treatments. The results indicate that the Test 1B （Ipratropium Bromide HFA pMD1, CiplaLtd.） is non inferior to the Reference lB.展开更多
OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METH...OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.展开更多
文摘Ipratropium bromide （IB） is an effective treatment for reversible bronchospasm associated with COPD. Cipla Ltd. hasdeveloped a formulation of lpratropium bromide pMDI （Test IB） which is designed to be equivalent to the originator product Atrovent HFA pMDI （Reference IB） as a cost effective alternative for the treatment of COPD. The objective of the study was to establishnon-inferiority of the Test 1B to Reference 1B in patients with stable COPD. In this multicenter, randomized, double-blind, doubledummy, parallel group study, patients aged 〉 40 years were randomized to receive 2 puffs three times daily （TID） of either the Test IBor Reference IB for 12 weeks. The primary endpoint was the change from pre dose to post dose FEVj at 90 min at the end of 12 weeks.Secondary endpoints included FVC, symptom score, rescue medication use and St. George＇s Respiratory Questionnaire （SGRQ）.Safety and tolerability included evaluation of adverse events （AEs）, vital signs assessments, physical examination and any change inconcomitant medications. A total of 395 patients were randomized to either the Test IB （n = 199） or the Reference IB （n = 196）; themajority of patients were male with a mean pre-bronchodilator FEV1 （% predicted） of 60%. The per protocol set comprised of 258patients （n = 129 in each treatment group）. The mean treatment difference between the Test IB and Reference 1B for the primaryendpoint （mean change in FEV1 from pre-dose to 90 rain post dose at 12 weeks） was -0.003 L and the lower limit of the 95% confidenceinterval （CI） for the difference between the two products was -0.041 Lwhich is greater than the predefined non inferiority limit of-0.100 L. No significant difference was seen between the Test IB and Reference IB for any secondary efficacy variables. The AEprofile was also comparable between the two treatments. The results indicate that the Test 1B （Ipratropium Bromide HFA pMD1, CiplaLtd.） is non inferior to the Reference lB.
文摘OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.
