Liver Impairment and Renal Impairment Related to COPD
San Diego—Patients with chronic obstructive pulmonary disease (COPD) who also had mild and moderate liver impairment or severe renal impairment tolerated a single orally-inhaled dose of olodaterol, according to 2 single-center, open-label trials.
Results were presented during poster sessions at the ATS conference. The 2 posters were titled: (1) Pharmacokinetics/Pharmacodynamics and Safety Analysis of a Single Dose of Olodaterol (30 μg Administered via the Respimat® Soft Mist™ Inhaler) in Patients with Severe Renal Impairment; and (2) Pharmacokinetics/Pharmacodynamics and Safety Analysis of a Single Dose of Olodaterol Administered via the Respimat® Soft Mist™ Inhaler in Patients with Mild and Moderate Liver Impairment.
In January 2013, the FDA’s Pulmonary-Allergy Drugs Advisory Committee recommended the approval of olodaterol to treat COPD based on results of 10 phase 3 trials, including trials that lasted 6 weeks and 48 weeks. However, the FDA has not yet approved the drug, a once-daily long-acting beta2-agonist that is administered through an inhaler.
According to the World Health Organization, an estimated 201 million people worldwide have COPD, a heterogeneous disease characterized by airflow limitation. COPD is not fully reversible, but it is preventable and treatable. Major risk factors for COPD include tobacco smoking, indoor and outdoor air pollution, and occupational dusts and chemicals. The Global Initiative for Obstructive Lung Diseases defines COPD as a ratio of <70% when dividing the post-bronchodilator forced expiratory volume in 1 second by the forced vital capacity.
In these studies, the researchers compared healthy subjects with those who had liver or renal impairment. They defined severe renal impairment as a creatinine clearance of <30 mL/min, normal renal function as creatinine clearance of >80 mL/min, mild liver impairment as a Child-Pugh Score of 5 to 6 points, and moderate liver impairment as a Child-Pugh Score of 7 to 9 points. Patients included in the study were 21 to 75 years of age.
The renal impairment trial included 8 patients with severe renal impairment and 14 healthy patients. Each patient received 30 μg of olodaterol via the inhaler. For most patients, potassium plasma levels decreased slightly from baseline to 30 to 40 minutes after dosing. Patients with renal impairment had an average systemic exposure to olodaterol 1.4 times higher compared with healthy patients. There were no differences between the groups in safety, tolerability, or systemic pharmacodynamics parameters. The only adverse events were mild to moderate in severity, and none were drug-related.
The liver impairment trial included 8 patients with mild liver impairment, 8 patients with moderate liver impairment, and 16 healthy patients who had normal hepatic function. Patients with liver impairment received 20 μg of olodaterol via the inhaler, while healthy patients received 30 μg of olodaterol via the inhaler. For most patients, potassium plasma levels decreased slightly from baseline to 30 to 40 minutes after dosing. There were no severe, serious, or significant adverse events in any of the patients, although 2 patients with moderate liver impairment had decreased blood potassium levels that were drug-related. The authors noted that compared with patients with normal liver function, those with impaired liver function did not change the systemic exposure to olodaterol.
These studies were funded by Boehringer Ingelheim.
