FDA Worried About Drugs’ Testicular Toxicity
Companies developing therapies that may have an adverse effect on the testes should conduct clinical trials to pin down the toxicity and whether it is reversible, the FDA says.
The primary endpoint of such trials should be the percentage of patients who experience a 50 percent or greater decline in sperm concentration compared to baseline and 13 weeks after starting the trial drug, or at 26 weeks for chronically administered drugs, according to draft guidance released Thursday.
Secondary endpoints should include changes in ejaculate volume, all changes from baseline in sperm concentration, total sperm per ejaculate, motility and morphology.
Patients whose sperm concentration drops 50 percent or more should be reevaluated 13 weeks after stopping the trial to assess recovery. Drugs with particularly long half-lives may require a longer recovery period, the agency says.
The FDA recommends randomized, double-blind, placebo-controlled, parallel arm trials with 200 men receiving drug or placebo. Sponsors should discuss the study design and risk mitigation and monitoring plans during pre-IND meetings with the agency.
When presenting results, drugmakers should include tables showing shift analyses from baseline to week 13 or 26 for each primary and secondary endpoint, along with a discussion of potential recovery during the drug-free follow-up period.
To view the draft guidance, go to www.fdanews.com/07-17-15-TesticularToxicity.pdf. — Kellen Owings