OBJECTIVES: Insulin exposure after inhalation has been reported to be altered significantly in subjects with chronic obstructive pulmonary disease (COPD). In this study, the rate and extent of insulin exposure was compared in healthy volunteers and subjects with COPD following administration of Technosphere * Insulin (TI), a dry powder insulin formulation for pulmonary delivery. METHODS: Insulin pharmacokinetics were evaluated in an open-label, single-dose, hyperinsulinemic-euglycemic glucose clamp study in 19 nondiabetic, nonsmoking healthy subjects (mean age [±SD] = 50.9 ± 14.1 years, body mass index = 29.1 ± 3.5 kg/m(2), forced expiratory volume in 1 second (FEV(1)) = 3.52 ± 1.02 L) and 17 nondiabetic subjects with mild-to-moderate COPD (mean age = 60.0 ± 9.0 years, body mass index = 28.5 ± 5 kg/m(2), FEV(1) = 2.56 ± 0.83 L). Subjects received a single 30-U dose of TI. Serial blood samples were obtained for insulin and C-peptide determination through 480 min after dosing. Insulin concentrations were adjusted for endogenous insulin by C-peptide correction; pharmacokinetic parameters were estimated using the corrected values. RESULTS: For the COPD and non-COPD groups, respectively, mean peak insulin (C(max)) was 34.7 µU/mL and 39.5 µU/mL (p = 0.29), median t(max) was 15 and 12 min (p = 0.24), and mean insulin exposure from time 0 to 240 min (AUC(0-240)) was 2037 µU/mL · min and 2279 µU/mL · min (p = 0.47). Cough was the most common respiratory adverse event observed. One instance of hypoglycemia was reported and was attributed to trial procedure. CONCLUSIONS: The rapid insulin absorption and the resulting insulin pharmacokinetic profile following TI inhalation were not significantly altered in the mild-to-moderate COPD population studied; however, long-term safety and efficacy of TI have not been established in patients with mild or moderate COPD. Longer-term experience is needed to fully characterize the effects of COPD on insulin PK following TI administration.
OBJECTIVES:Insulin exposure after inhalation has been reported to be altered significantly in subjects with chronic obstructive pulmonary disease (COPD). In this study, the rate and extent of insulin exposure was compared in healthy volunteers and subjects with COPD following administration of Technosphere * Insulin (TI), a dry powder insulin formulation for pulmonary delivery. METHODS:Insulin pharmacokinetics were evaluated in an open-label, single-dose, hyperinsulinemic-euglycemic glucose clamp study in 19 nondiabetic, nonsmoking healthy subjects (mean age [±SD] = 50.9 ± 14.1 years, body mass index = 29.1 ± 3.5 kg/m(2), forced expiratory volume in 1 second (FEV(1)) = 3.52 ± 1.02 L) and 17 nondiabetic subjects with mild-to-moderate COPD (mean age = 60.0 ± 9.0 years, body mass index = 28.5 ± 5 kg/m(2), FEV(1) = 2.56 ± 0.83 L). Subjects received a single 30-U dose of TI. Serial blood samples were obtained for insulin and C-peptide determination through 480 min after dosing. Insulin concentrations were adjusted for endogenous insulin by C-peptide correction; pharmacokinetic parameters were estimated using the corrected values. RESULTS: For the COPD and non-COPD groups, respectively, mean peak insulin (C(max)) was 34.7 µU/mL and 39.5 µU/mL (p = 0.29), median t(max) was 15 and 12 min (p = 0.24), and mean insulin exposure from time 0 to 240 min (AUC(0-240)) was 2037 µU/mL · min and 2279 µU/mL · min (p = 0.47). Cough was the most common respiratory adverse event observed. One instance of hypoglycemia was reported and was attributed to trial procedure. CONCLUSIONS: The rapid insulin absorption and the resulting insulin pharmacokinetic profile following TI inhalation were not significantly altered in the mild-to-moderate COPD population studied; however, long-term safety and efficacy of TI have not been established in patients with mild or moderate COPD. Longer-term experience is needed to fully characterize the effects of COPD on insulin PK following TI administration.
Authors: Janet B McGill; Anne Peters; John B Buse; Susanne Steiner; Tiffany Tran; Frank M Pompilio; David M Kendall Journal: Clin Drug Investig Date: 2020-10 Impact factor: 2.859