Operating Characteristics of a Partial-Block Randomized Crossover Bioequivalence Study for Dutasteride, a Drug with a Long Half-Life: Investigation Through Simulation and Comparison with Final Results
| Autor: | Jake J. Thiessen, Gengqian Cai, Michael J. Fossler, Charlotte A. Baidoo |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Drug Computer science media_common.quotation_subject Crossover Bioequivalence chemistry.chemical_compound 5-alpha Reductase Inhibitors Tamsulosin medicine Econometrics Humans Computer Simulation Pharmacology (medical) media_common Block (data storage) Pharmacology Cross-Over Studies Dutasteride Crossover study Reliability engineering Therapeutic Equivalency chemistry Sample size determination Area Under Curve Azasteroids Half-Life medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 50:1142-1150 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270009355155 |
| Popis: | Studies to establish bioequivalence (BE) of a drug are important elements in support of drug applications. A typical BE study is conducted as a single dose, randomized, 2-period crossover design. For drugs with long half lives (≥ 48 hours) and evaluation of multiple BE objectives in 1 trial, this design may not be adequate. A parallel design may then be a more appropriate choice. However, parallel designs require increased sample size, which can become substantial. One option that is a compromise between the complete randomized block design and the parallel design is a partial-block crossover design. This approach came about during the development of a combination of dutasteride and tamsulosin. Previous experience with performing single-dose dutasteride studies suggested that 28 days of washout is needed between treatments because of its half-life of 7–9 days. Simulations were performed to assess the operating characteristics of this design using a previously developed PK model. Four scenarios were developed, and each scenario was simulated 500 times. The results showed that this design demonstrated acceptable consumer and producer risk. Partial-block crossover designs should be considered for studies when the half-life of the drug is long and there are more than 2 periods. |
| Databáze: | OpenAIRE |
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