CHF 5259, an investigational drug, is an extra-fine inhaled therapy consisting of glycopyrronium (or glycopyrrolate) bromide (GB). Its active ingredient, glycopyrrolate, is a long acting muscarinic M3 receptor antagonist (LAMA). Muscarinic antagonists mediate bronchial smooth muscle contraction and the release of mucus in the aiways. CHF 5259 specifically targets the M3 receptor that is present in bronchial smooth muscle cells.

The treatment, now being tested in Phase 2 trials, is a dry powder delivered using a pressurized metered dose inhaler (pMDI). This consists of a handheld device with an attached mouthpiece that allows for the active ingredient to be inhaled directly into the lungs.

CHF 5259 is being developed by Chiesi Farmaceuitici for the treatment of COPD (chronic obstructive pulmonary disease).

CHF 5259 and clinical trials

A Phase 1 study (NCT01176851) evaluated the pharmacokinetics and bioavailability of CHF 5259 administered in two ways: by pMDI and intravenous (IV). Healthy participants were given a 100 µg dose of glycopyrrolate either by IV (Robinul injection) or CHF 5259 as a single pMDI dose. A number of adults treated with CHF 5259 also ingested charcoal to isolate the drug’s pulmonary bioavailability and prevent gastrointestinal absorbtion. Results showed that CHF 5259 pMDI was rapidly absorbed, with a concentration peak at five minute post-dose, and was safe and well-tolerated. Pharmacokinetics parameters were similar with and without charcoal block, suggesting limited gastrointestinal absorption.

One Phase 2 study (NCT02189577), completed in 2015, evaluated the efficacy and safety of CHF 5259. About 100 people with moderate to severe COPD were given 12.5 µg CHF 5259 inhaled therapy or placebo for four weeks. A one-week wash-out period was followed by crossover, in which placebo patients switched to treatment and vice versa. The trial’s primary measure was the change from baseline (study start) in FEV1 — the amount of air you can forcefully breathe out in one second — on day 28 (before morning dose was given).  Results showed “superior clinical benefits [of CHF 5259 pMDI] compared to placebo in COPD patients with moderate/very severe lung function” and a “good” safety profile.

Another Phase 2 study (NCT02680197, known as GlycoNEXT), evaluating the efficacy and safety of different doses of CHF 5259 (12.5, 25, 50 and 100 µg) is ongoing. About 262 people with moderate to severe COPD are enrolled, and trial is expected to end in early 2017. A primary goal is improvement in lung function as measured by changes in FEV1.

Side effects and other details

Common side effects of glycopyrrolate include dry mouth, difficulty in urinating, vision problems, dizziness, and headhaches. GB injection is used before surgery to reduce salivary, tracheobronchial, and pharyngeal secretions. The drug also lessens acidity in the stomach and can be used as combination therapy to treat ulcers in the stomach and small intestine.

CHF 5259 is also being tested in two Phase 2 studies (NCT02296411 and NCT02127866) as a possible treatment for asthma.

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