US-based biopharmaceutical firm Theravance has started the dose-ranging Phase IIb trial (0117) of its investigational inhaled long-acting muscarinic antagonist (LAMA) TD-4208, as a nebulised aqueous solution for the treatment of patients with moderate to severe chronic obstructive pulmonary disease (COPD).
The Phase IIb trial is designed to assess the bronchodilator effect, safety and tolerability of four doses of TD-4208 (including 44mcg, 88mcg, 175mcg, 350mcg) and placebo in patients with moderate to severe COPD.
In the trial, a total of 350 patients will be given one of four doses of TD-4208 inhalation solution or placebo once daily via a jet nebuliser for 28 days in a double-blind, parallel group study design.
Theravance senior vice president of research and development Mathai Mammen said: "We believe we have a significant opportunity to meet the needs of certain patients who may need or prefer nebulised therapy."
The trial's primary endpoint is trough forced expiratory volume in one second (FEV1) after the 28-day treatment period, while secondary endpoints include measurements of serial FEV1 on Day 28 and Day 1 and safety and tolerability assessments.
TD-4208 was discovered by the company through the application of multivalent design in a drug discovery programme dedicated to finding new medicines for respiratory diseases such as COPD and asthma.
TD-4208 has shown high specificity for muscarinic receptors, sustained activity in the lung after inhalation, and minimal systemic effects in preclinical trials.
The company's LAMA programme is aimed at developing a once-daily inhaled medicine in a nebuliser for the treatment of a subset of COPD patients who are underserved by current hand held products or prefer nebulised therapy.
TD-4208 has previously completed a multiple-dose Phase IIb trial (0091) and a single-dose Phase IIa trial in patients with moderate to severe COPD.
Image: Lung bulla as seen on CXR in a person with severe COPD associated with anti 1 antitrypsin deficiency. Photo: courtesy of James Heilman, MD.