Zydus Healthcare will proceed with a Phase III clinical trial for its fixed-dose combination (FDC) of glycopyrrolate and indacaterol maleate metered-dose inhalation, following a recommendation from the Subject Expert Committee (SEC) under the Central Drug Standard Control Organisation (CDSCO). The decision was made after the SEC reviewed Zydus Healthcare's bioequivalence (BE) study report and justification for a Phase III clinical trial waiver. This combination drug is aimed at providing long-term maintenance treatment for airflow obstruction in patients suffering from chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
The SEC's decision came after a thorough evaluation of the presented data, leading them to conclude that a Phase III clinical trial is necessary for the proposed FDC. Consequently, the expert panel has directed Zydus Healthcare to submit the Phase III clinical trial protocol to CDSCO for further review.
Clinical Context of Glycopyrrolate and Indacaterol
The combination of indacaterol and glycopyrrolate addresses the critical need for effective bronchodilation in COPD patients. COPD, a chronic lung disease, leads to bronchospasm, causing wheezing and breathing difficulties. Both indacaterol and glycopyrrolate are long-acting bronchodilators, offering sustained relief from these symptoms.
Glycopyrrolate, a racemic mixture of two enantiomers, functions as a long-acting muscarinic antagonist. It binds to muscarinic receptors in bronchial smooth muscle, preventing acetylcholine from binding and causing bronchoconstriction. Glycopyrrolate preferentially binds to M3 receptors, which are primarily responsible for bronchoconstriction in COPD. By blocking these receptors, glycopyrrolate improves lung function, reduces exacerbation risk, and alleviates breathlessness.
Indacaterol, an inhaled long-acting beta-2 adrenergic agonist, complements glycopyrrolate's action by relaxing bronchial smooth muscle and improving airflow. It stimulates adrenergic beta-2 receptors in the smooth muscle of the airways, increasing the diameter of constricted airways in asthma and COPD. Indacaterol's high affinity for lipid raft domains in the airway membrane contributes to its long-acting effect, with a rapid onset of action within 5 minutes.
