PMID- 27455840
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160726
LR  - 20240325
IS  - 2001-1326 (Print)
IS  - 2001-1326 (Electronic)
IS  - 2001-1326 (Linking)
VI  - 5
IP  - 1
DP  - 2016 Dec
TI  - Clinical trial considerations on male contraception and collection of pregnancy 
      information from female partner: update.
PG  - 23
LID - 10.1186/s40169-016-0103-8 [doi]
LID - 23
AB  - 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. The duration for highly effective contraception has 
      been extended from 74 to 90 days from the end of relevant systemic exposure. 
      Teratogenicity Pharmacokinetic considerations to estimate safety margins have 
      been contextualized with regard to over- and underestimation of the risk of 
      teratogenicity transmitted by a vaginal dose. The duration of male contraception 
      after the last dose takes into account the end of relevant systemic exposure if 
      measured, or a default period of five half-lives after last dose for small 
      molecules and two half-lives for immunoglobulins (mAbs). Measures to prevent 
      exposure of the conceptus via a vaginal dose apply to reproductively competent or 
      vasectomized men, unless measurements fail to detect the compound in seminal 
      fluid. CONCLUSION: Critical review of new guidance documents provides a 
      comparison across approaches and resulted in an update of our previous 
      publication. Separate algorithms for small molecules and monoclonal antibodies 
      are proposed to guide the recommendations for contraception for male trial 
      participants and pregnancy reporting from female partners. No male contraception 
      is required if the dose is below a defined threshold for genotoxic concern 
      applicable to small molecules. For men treated with teratogenic mAbs, condom use 
      to prevent exposure of a potentially pregnant partner is unlikely to be 
      recommended because of the minimal female exposure anticipated following a 
      vaginal dose. The proposed safety margins for teratogenicity may evolve with 
      further knowledge.
FAU - Banholzer, Maria Longauer
AU  - Banholzer ML
AD  - Safety Risk Management, Licensing & Early Development, F. Hoffmann-La Roche AG, 
      Basel, Switzerland. maria.longauer_banholzer@roche.com.
FAU - Wandel, Christoph
AU  - Wandel C
AD  - Safety Risk Management, Licensing & Early Development, F. Hoffmann-La Roche AG, 
      Basel, Switzerland.
FAU - Barrow, Paul
AU  - Barrow P
AD  - Pharma Research & Early Development, Roche Innovation Center Basel, 
      Pharmaceutical Sciences, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Mannino, Marie
AU  - Mannino M
AD  - Safety Risk Management, Licensing & Early Development, F. Hoffmann-La Roche Ltd, 
      New York, NY, USA.
FAU - Schmitt, Georg
AU  - Schmitt G
AD  - Pharma Research & Early Development, Roche Innovation Center Basel, 
      Pharmaceutical Sciences, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Guerard, Melanie
AU  - Guerard M
AD  - Pharma Research & Early Development, Roche Innovation Center Basel, 
      Pharmaceutical Sciences, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Muller, Lutz
AU  - Muller L
AD  - Pharma Research & Early Development, Roche Innovation Center Basel, 
      Pharmaceutical Sciences, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Greig, Gerard
AU  - Greig G
AD  - Pharma Research & Early Development, Roche Innovation Center Basel, Clinical 
      Pharmacology, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Amemiya, Kenjie
AU  - Amemiya K
AD  - Non-Clinical Safety Department, Genentech Inc, South San Francisco, CA, USA.
FAU - Peck, Richard
AU  - Peck R
AD  - Pharma Research & Early Development, Roche Innovation Center Basel, Clinical 
      Pharmacology, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Singer, Thomas
AU  - Singer T
AD  - Pharma Research & Early Development, Roche Innovation Center Basel, 
      Pharmaceutical Sciences, F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Doessegger, Lucette
AU  - Doessegger L
AD  - , Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20160725
PL  - United States
TA  - Clin Transl Med
JT  - Clinical and translational medicine
JID - 101597971
EIN - Clin Transl Med. 2016 Dec;5(1):30. PMID: 27520795
PMC - PMC4960246
OTO - NOTNLM
OT  - Clinical trials
OT  - Genotoxicity
OT  - Male contraception
OT  - Paternal exposure
OT  - Teratogenicity
EDAT- 2016/07/28 06:00
MHDA- 2016/07/28 06:01
PMCR- 2016/07/25
CRDT- 2016/07/27 06:00
PHST- 2016/04/11 00:00 [received]
PHST- 2016/06/24 00:00 [accepted]
PHST- 2016/07/27 06:00 [entrez]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2016/07/28 06:01 [medline]
PHST- 2016/07/25 00:00 [pmc-release]
AID - 10.1186/s40169-016-0103-8 [pii]
AID - 103 [pii]
AID - 10.1186/s40169-016-0103-8 [doi]
PST - ppublish
SO  - Clin Transl Med. 2016 Dec;5(1):23. doi: 10.1186/s40169-016-0103-8. Epub 2016 Jul 
      25.