SOLICITATION NOTICE
A -- Bioequivalence Studies of Inhaled Corticosteroids
- Notice Date
- 4/30/2004
- Notice Type
- Solicitation Notice
- NAICS
- 541710
— Research and Development in the Physical, Engineering, and Life Sciences
- Contracting Office
- Department of Health and Human Services, Food and Drug Administration, Office of Acquisitions and Grants Services, 5630 Fishers Lane, Room 2129, Rockville, MD, 20857-0001
- ZIP Code
- 20857-0001
- Solicitation Number
- 223-04-3003
- Response Due
- 7/5/2004
- Archive Date
- 7/20/2004
- Point of Contact
- Hamilton Brown, Contract Specialist, Phone (301) 827-7043, Fax (301) 827-7101,
- E-Mail Address
-
hbrown@oc.fda.gov
- Description
- Establishing bioequivalence (BE) of inhaled corticosteroids (ICS) requires a study design that is sensitive to dose differences. Published dose-response and potency studies have utilized parallel designs for evaluation of ICS response because carryover between treatments prevented the use of crossover studies. However, experience shows that for ICS, parallel designs generally lack sensitivity to distinguish differences in potency (i.e., shallow dose-response at the labeled dose and multiples thereof), and possess high variability. Based on parallel design studies, the estimated sample size for documentation of BE is 1000 subjects or more. At present, no validated BE methods with acceptable sensitivity and precision are available for ICS. In 2001, Richard Ahrens, University of Iowa, (RC Ahrens, ME Teresi, S-H Han et al., ?Asthma stability after oral prednisone: A clinical model for comparing inhaled steroid potency,? Am J Respir Crit Care Med, 2001;164:1138-45) proposed a novel clinical model for determining relative potency of ICS using a crossover study design, in which the subjects serve as their own controls, thus increasing study power. The study uses a wash-in of high dose steroid to equalize carryover between treatment periods, thus allowing a crossover design. Based on pilot study data using the Ahrens? model, the number of subjects needed for a BE study is estimated to be fewer than 100, an order of magnitude lower than the number needed in a parallel design. The improved study power results in a study design that appears practical to establish BE. FDA?s proposed Phase I contract will refine the study design published by Ahrens et al. in an effort to make the design suitable for establishment of bioequivalence. The phase I study will consist of a randomized crossover dose-response study of three different doses of fluticasone propionate MDI, 44 mcg/actuation, in a four period study with duplication of one of the doses. The proposed dose-response design, when applied to a BE study, is anticipated to involve three doses of reference listed drug (RLD), and at least one dose of test product, for a minimum of four study periods. A lengthy, four period design will involve the potential for subject dropouts, changes in asthma status over time, concurrent upper respiratory tract infection, and increased steroid exposure. In order to include these practical issues in the dose-response study, the RLD at the same dose that would be used for the test product in a BE study, is duplicated. Inclusion of the replicated dose in the Phase 1 study will enable examination of intra-subject variability. Each of the three doses will be from the same strength MDI. The 44 mcg/actuation strength, rather than the 110 or 220 mcg/actuation strength, is chosen to enable characterization of dose-response in the rapidly rising region of the dose-response curve. At least 24 asthmatic subjects will be enrolled and the study endpoints measured at scheduled times, including 1, 2, 3 and 4 weeks following initiation of ICS will include raw spirometry outcomes and decrease in spirometry outcomes from maximal response. Analysis of the Phase I results will attempt to address many of the following issues: (1) evaluation of whether a crossover rather than a parallel study design is adequate to obtain acceptable study power, (2) evaluation of intra-subject variability of the reference product and identification of acceptance limits for the phase 2 study, (3) an improved understanding of the dose-response in terms of optimal size doses to maximize study power and minimize the subject sample size, (4) improvement in the variance of spirometric measurements by conduct of critical study phases in a clinical center rather than in the home, (5) duration of each period of the randomized phase, 1, 2, 3 or 4 weeks, and (6) inclusion criteria which may enrich the study population. In order to assess the power of the study at earlier times of ICS dosing, study endpoints at 1 and 2 weeks will also be determined. At completion of phase I, an optimal design which can be studied in phase II of the project, is anticipated. Phase II will apply the refined method to a bioequivalence study to confirm the utility of the method. Phase II will be a crossover BE study to confirm the utility of the new method. This research is anticipated to provide a method for conduct of a sensitive study to document the BE of a test product to the reference listed drug or precursor product. Availability of the method may also be useful to assure bioequivalence of reformulated NDA products. Although the study will use fluticasone propionate MDI as the model drug product, the study results are anticipated to be broadly applicable to the entire class of ICS. A successful outcome of both Phases I and II of the project will enable the agency for the first time to be able to recommend a suitable BE method for ICS. The BE method will be published in a draft guidance for industry. It is anticipated that a cost reimbursement type contract will be made for a period of one and one-half_(1.5) years in September 2004. This is not a Request for Proposals (RFP). THIS SOLICITATION WILL BE AVAILABLE ELECTRONICALLY ONLY. Request for Proposal (RFP) No. 223-04-3003 will be available electronically and may be accessed through the FedBizOpps (URL: http://www.fedbizopps.gov) 15 or more calendar days after the issuance of this synopsis. OFFERORS ARE RESPONSIBLE FOR ROUTINELY CHECKING THIS WEBSITE FOR ANY POSSIBLE SOLICITATION AMENDMENTS THAT MAY BE ISSUED. NO INDIVIDUAL NOTIFICATION OF ANY AMENDMENTS WILL BE PROVIDED. All responsible sources may submit a proposal, which shall be considered by the agency.
- Place of Performance
- Address: Contractor's site
- Record
- SN00577534-W 20040502/040430211804 (fbodaily.com)
- Source
-
FedBizOpps.gov Link to This Notice
(may not be valid after Archive Date)
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