distribution of pomalidomide into semen of healthy male subjects after multiple doses

Yan Li,1 Xiaomin Wang,2 Liangang Liu,3 Josephine Reyes,1 Maria Palmisano,1 Simon Zhou1 1Translational Development and Clinical Pharmacology, Celgene Corporation, Summit, NJ, USA; 2Non-Clinical Development, Celgene Corporation, Summit, NJ, USA; 3Biometrics and Data Operations, Celgene Corporation, Summit, NJ, USA Objective: To assess whether pomalidomide can distribute into human semen and its duration in human semen. Method: A phase 1, randomized, double-blind, placebo-controlled study (CC-4047-CP-006) was conducted to evaluate the safety, tolerability, and pharmacokinetics of pomalidomide (CC-4047) following multiple daily doses in healthy male subjects. Semen samples were collected on Day −1 and 4 hours after dosing on Day 4 to quantify the pomalidomide concentrations in ejaculate after multiple oral doses of pomalidomide. Result: Our study showed that pomalidomide was present in male subjects’ semen samples, and the average amount of pomalidomide in a single ejaculate 4 hours after dosing was less than 0.0022% of the daily 2 mg dose. There was a good correlation between the semen concentrations and the plasma concentrations, suggesting that the plasma concentration may be the main driving force for the distribution of pomalidomide into the seminal reservoirs. Simulation results suggest that pomalidomide was undetectable in semen 48 hours after stopping dosing. Conclusion: Based on the results from this study, the pomalidomide prescribing information approved by the US Food and Drug Administration includes a statement that “pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Male patients taking POMALYST must not donate sperm.” Keywords: pomalidomide, distribution, semen, teratogen, kinetics