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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
Author(s) -
Cai Gengqian,
Thiessen Jake J.,
Baidoo Charlotte A.,
Fossler Michael J.
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009355155
Subject(s) - bioequivalence , crossover study , dutasteride , crossover , medicine , randomized controlled trial , block (permutation group theory) , sample size determination , mathematics , computer science , pharmacology , statistics , pharmacokinetics , surgery , machine learning , placebo , prostate , alternative medicine , geometry , pathology , cancer
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.