MP32-10 BASELINE CORRECTION IN TESTOSTERONE BIOEQUIVALENCE STUDY

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Evaluation1 Apr 2014MP32-10 BASELINE CORRECTION IN TESTOSTERONE BIOEQUIVALENCE STUDY LaiMing Lee, SangAeh Park, Myong-Jin Kim, Chongwoo Yu, and Li Li LaiMing LeeLaiMing Lee More articles by this author , SangAeh ParkSangAeh Park More articles by this author , Myong-Jin KimMyong-Jin Kim More articles by this author , Chongwoo YuChongwoo Yu More articles by this author , and Li LiLi Li More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.940AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES For applicants seeking approval of a drug product, a bioequivalence (BE) study may be required if an application relies on FDA’s finding of safety and/or effectiveness for the reference listed drug (RLD). Testosterone (T), an anabolic steroid, is approved to treat men with hypogonadism. For approval of a T product, an endogenous substance drug product, the demonstration of BE against an RLD is complicated by endogenous T production. To rule out the influence of endogenous T, baseline T concentrations are subtracted from the total T concentrations for each subject after the drug product is administered. Pharmacokinetic and statistical analyses are performed on both uncorrected and corrected data as appropriate. Determination of BE between a test and RLD is based on the baseline-corrected T data. BE assessment may be complicated if an individual’s endogenous T concentrations change day-to-day or exhibit a circadian pattern. Currently, there are no consistent or data-driven approaches to assessing and reporting baseline T concentrations. The objectives of this study was to use FDA in-house data to assess baseline T characteristics and to determine the optimal baseline correction method for evaluation of BE of T products. METHODS FDA in-house data from T clinical trials (pivotal BE and phase 1 studies) were collected and analyzed for baseline T concentrations in hypogonadal men. We assessed the presence of a circadian rhythm in hypogonadal men and intra-subject variability of endogenous T between treatment periods. RESULTS A total of 266 hypogonadal men from 4 new drug applications submitted to FDA were analyzed. Data were obtained from 3 BE studies and 3 relative bioavailability studies. The age and body mass index in hypogonadal men ranged from 18 to 80 years and 15 to 35 kg/m2, respectively. Preliminary results show that, in general, baseline T concentrations in hypogonadal men fluctuated less than 100 ng/dL over a 12- to 24-hour period pre-treatment. Up to 200% intra-subject variability was seen when endogenous T concentration measurements were taken at the same time of the day with several days of separation (i.e., 108 versus 325 ng/dL taken at 10 am on Days 1 and 8). CONCLUSIONS Correction of baseline T concentration is needed for the assessment of BE of T products. Circadian rhythm is not significant in hypogonadal men compared to intra-subject variability. Therefore, the need to take extensive blood samples over 24 hours to characterize baseline T concentrations may not be necessary. However, due to the intra-subject variability, assessment of baseline T is needed before each treatment period. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e334 Advertisement Copyright & Permissions© 2014MetricsAuthor Information LaiMing Lee More articles by this author SangAeh Park More articles by this author Myong-Jin Kim More articles by this author Chongwoo Yu More articles by this author Li Li More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...