Predictivity of Nonclinical Male Reproductive Findings for Human Effects

Abstract

Background: Testing of pharmaceutical products for reproductive toxicity in male laboratory animals is required for registration.

Methods: We evaluated whether the results of studies showing male reproductive toxicity in experimental animals was predictive of reproductive effects in men participating in clinical trials. We surveyed companies for information on pharmaceutical candidates that had shown male reproductive toxicity in nonclinical studies for which there was information on male reproductive effects in clinical trials.

Results: Among 12 pharmaceutical candidates submitted by five companies, only one compound that had shown male reproductive toxicity in experimental animals also demonstrated reproductive toxicity in men.

Conclusion: In this sample of compounds, nonclinical studies appeared to over-predict reproductive toxicity in men. We identified possible reasons for the apparent lack of predictivity of the experimental animal studies. Birth Defects Research 110:17-26, 2018. © 2017 Wiley Periodicals, Inc.

Keywords: animal-human concordance; male reproduction; nonclinical studies; reproductive toxicity; testicular toxicity.