RESUMO
Systemic therapeutic protein delivery through the lungs could potentially replace delivery by injection, but safety needs to be established in patients with known pulmonary disease. This study determined the short-term safety profile of recombinant human growth hormone (rhGH; somatropin) inhalation therapy in clinically stable adult subjects with mild to moderate asthma and methacholine sensitivity. This randomized, placebo-controlled study had two phases: (1) an escalating 3-dose, 4-day/dosage tolerance phase; and (2) a 14-day, crossover design comparability phase. Noninferiority in maintaining forced expiratory volume in 1 second (FEV(1)) was tested for somatropin inhalation powder (SIP) compared with subcutaneously injected rhGH (Hsc) and inhaled placebo. Lung hyperresponsiveness was assessed by methacholine bronchoprovocative challenge, and adverse events (AEs) were recorded. Eight and 18 subjects enrolled in the first and second phases, respectively. Noninferiority of SIP compared with Hsc and placebo was established for FEV(1) after the first and last doses, and noninferiority of SIP compared with Hsc for methacholine challenge was established after the first dose. Pulmonary uptake and systemic distribution of SIP was confirmed by increased serum insulin-like growth factor I levels. Mild, nonprogressive cough and nasal congestion occurred more commonly with SIP. All other treatment-emergent AEs were mild, similar across active treatment groups, and consistent with rhGH treatment. In clinically stable adults with mild to moderate asthma, no significant changes in pulmonary function or worsening of asthma complaints occurred during SIP treatment. Future studies of SIP may enroll subjects with mild to moderate asthma for longer-term evaluation of safety and efficacy.
