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Pharmacokinetics of Subcutaneous IgPro20 in Patients with Primary Immunodeficiency.
- Source :
- Clinical Pharmacokinetics; 2011, Vol. 50 Issue 6, p405-414, 10p, 2 Diagrams, 2 Charts, 3 Graphs
- Publication Year :
- 2011
-
Abstract
- Background and Objectives: Immunoglobulin replacement is a standard therapy for patients with primary immunodeficiencies. Subcutaneous administration of immunoglobulin offers more constant IgG levels than intravenous administration and simplifies administration for some patients. Use of L-proline as an excipient contributes to the stability of highly concentrated IgG preparations. The aims of the present study were to evaluate the pharmacokinetics of IgPro20 (Hizentra®), a new 20% subcutaneous IgG solution, and compare the area under the serum concentration-time curve (AUC) with that of a similar intravenous 10% IgG solution (IgPro10; Privigen®). At the request of the US FDA, an algorithm for determining IgG trough level ratios (TLRs) was developed in order to provide physicians with a practical tool for monitoring doses during steady-state IgPro20 therapy. Methods: This was a prospective, open-label, multicentre, single-arm, phase III clinical trial conducted in the US. The study was performed in a primary-care setting. Eligible patients were males or females aged 6-75 years with a primary immunodeficiency (common variable immunodeficiency or X-linked agamma-globulinaemia) who had received regular treatment with IgPro10 for at least 3 months prior to entering this study and had achieved serum trough concentration (C<subscript>trough</subscript>) values ≥>5 g/L. IgPro20 was administered subcutaneously once weekly at initial doses equivalent to 130% of patients' previous doses, based on the results obtained in a Vivaglobin® study and due to an FDA request. After run-in, each patient's dose was adjusted to achieve an AUC comparable to that achieved with IgPro10 administered intravenously. Results: Eighteen patients completed the study. Mean IgPro20:IgPro10 dose ratio (dose adjustment co-efficient) was 1.53 (range 1.26-1.87). The resulting mean AUCs were 105.6g · day/L for IgPro20 versus 103.2 g · day/L for IgPro10 (geometric mean ratio 1.002; lower one-sided 95% confidence limit [CL] 0.951). Thus, the primary endpoint of the study was met, as this result exceeded the pre-specified criterion of the lower one-sided 95% CL of ≥0.8 for non-inferiority. At these AUCs, which were considered equivalent, the mean IgPro20 : IgPro10 TLR, determined by the developed algorithm, was 1.29 (range 1.18-1.73). Titres of specific antibodies tested were well above respective product specifications, suggesting that protection against infection would be effective. Conclusion: Steady-state AUCs with subcutaneous IgPro20 and intravenous IgPro10 were equivalent. Mean dose adjustment coefficient and mean TLR can be used for initial dose conversion without risk of under- protection but vary too widely to be considered measures of equivalence. Trial registration number (clinicaltrials.gov): NCT00419341 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03125963
- Volume :
- 50
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Clinical Pharmacokinetics
- Publication Type :
- Academic Journal
- Accession number :
- 63616760
- Full Text :
- https://doi.org/10.2165/11587030-000000000-00000