Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update.

Background: This is an update to our 2012 publication on clinical trial considerations on male contraception and collection of pregnancy information from female partner, after critical review of recent (draft) guidances released by the International Council for Harmonisation [ICH] the Clinical Trial Facilitation Group [CTFG] and the US Food & Drug Administration [FDA].

Methods: Relevant aspects of the new guidance documents are discussed in the context of male contraception and pregnancy reporting from female partner in clinical trials and the approach is updated accordingly.

Results: Genotoxicity The concept of a threshold is introduced using acceptable daily intake/permissible daily exposure to define genotoxicity requirements, hence highly effective contraception in order to avoid conception.

Clinical development methodology for infusion-related reactions with monoclonal antibodies.

Infusion-related reactions (IRRs) are common with monoclonal antibodies (mAbs) and timely related to drug administration and have been reported as anaphylaxis, anaphylactoid reactions and cytokine release syndrome, among other terms used. We address risk management measures for individual patients and for the study and propose a consistent reporting approach in an attempt to allow cross-molecule comparisons. Once the symptoms of IRR have resolved, the mAb may be restarted.

Clinical trial considerations on male contraception and collection of pregnancy information from female partners.

Background: There is little guidance regarding the risk of exposure of pregnant women/ women of childbearing potential to genotoxic or teratogenic compounds via vaginal dose delivered through seminal fluid during sexual intercourse.

Method: We summarize current thinking and provide clinical trial considerations for a consistent approach to contraception for males exposed to genotoxic and/or teratogenic compounds or to compounds of unknown teratogenicity, and for collection of pregnancy data from their female partners.

Results: Where toxicity testing demonstrates genotoxic potential, condom use is required during exposure and for 5 terminal plasma half-lives plus 74 days (one human spermatogenesis cycle) to avoid conception.