Bioequivalence of a novel omalizumab solution for injection compared with the standard lyophilized powder formulation

Aim: To determine the pharmacokinetic (PK) and pharmacodynamic (PD) comparability of a novel solution for injection (solution) and the reference lyophilized powder formulation (powder) of omalizumab. Methods: In this open-label, parallel-group study, adult atopic subjects (serum immunoglobulin [Ig] E 30−300 IU/ml; body weight, 40−90 kg) received a single subcutaneous dose (150 or 300 mg) of solution or powder omalizumab. Serum concentrations of total omalizumab, free and total IgE and safety were determined up to 84 days post dose. Bioequivalence was examined for dose-normalized parameters of omalizumab in serum: maximum concentration (Cmax), area under the concentration-time curve up to the last quantifiable concentration (AUC0-tlast) and up to infinity (AUC0-inf). Bioequivalence was concluded if the 90% confidence interval (CI) of the ratio of solution vs. powder geometric means was entirely contained within 0.8–1.25. Results: 155 subjects were randomized and dosed (62.6% female; mean age, 34.7 years). Systemic exposure to omalizumab was similar for the two formulations at both doses. PK bioequivalence was demonstrated (n = 153): Cmax, ratio of geometric means: 1.01 (90% CI: 0.95–1.08); AUC0-tlast, 0.98 (0.92–1.05); AUC0-inf, 0.98 (0.91–1.05). Omalizumab mean elimination half-life: 22.1 days for solution; 22.9 days for powder. PD parameters (n = 154) of free and total IgE in serum were comparable between formulations; each produced a 95% reduction from screening in free IgE. Most common adverse events (AEs): headache (23.9%), sinus congestion (8.4%). No serious AEs were reported. Conculsions: The novel, ready-to-use omalizumab solution formulation is bioequivalent to the reference lyophilized powder formulation

Safety, tolerability and pharmacokinetics of single escalating doses of indacaterol, a once-daily beta2-agonist bronchodilator, in subjects with COPD.

Objectives: To assess the safety and tolerability of 4 doses of indacaterol, a once-daily beta2-agonist, in subjects with chronic obstructive pulmonary disease (COPD). The 24-h bronchodilator effect and pharmacokinetics of indacaterol were also investigated. Methods: 16 subjects aged 43 - 72 years with mild/moderate COPD were each given single doses of indacaterol of 400, 1,000, 2,000 and 3,000 µg, via a single-dose dry powder inhaler. Results: Changes from predose (400, 1,000, 2,000, 3,000 µg doses, respectively) were as follows. Maximum mean decreases in fasting (up to 2 h post-dose) serum potassium were 0.12, 0.30, 0.38, 0.26 mmol/l; maximum mean increases (up to 2 h post-dose) in fasting serum glucose were 0.12, 0.40, 0.87, 1.01 mmol/l. The maximum increase in heart rate (by 3, 6, 12, 13 beats/min, respectively) was within 1 h post-dose. No clinically significant electrocardiogram abnormalities were reported. Most adverse events were mild or moderate, with none considered serious or leading to withdrawal. Indacaterol was rapidly absorbed and displayed multiphasic disposition kinetics. The terminal elimination phase with a half-life of 50 - 63 h could only be seen for doses of 1,000 µg or higher. Mean systemic exposure to indacaterol (AUC0-24) increased by ~ 9-fold from 400 to 3,000 µg. Conclusion: Even at doses far in excess of the therapeutic range, indacaterol had minimal systemic effects; such changes would be considered within safe limits for a single dose

Effect of renal impairment on the pharmacokinetics and pharmacodynamics of desirudin.

To investigate the pharmacokinetics and pharmacodynamics of desirudin in subjects with various degrees of renal impairment in comparison with subjects with normal renal function

Pharmacokinetics of valsartan in patients with liver disease.

Valsartan (CGP 48933), an orally active angiotensin II antagonist, is eliminated mainly by hepatic clearance. To characterize the compound(s) excreted in the bile, biliary excretion of valsartan was investigated by collection of bile after an intravenous dose of valsartan. In addition, to determine the exposure to valsartan when liver function is impaired, a pharmacokinetic study (open, single dose) was performed in patients with mild and moderate impairment of liver function