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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960246/ https://www.ncbi.nlm.nih.gov/pubmed/27455840 http://dx.doi.org/10.1186/s40169-016-0103-8 |
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author | Banholzer, Maria Longauer Wandel, Christoph Barrow, Paul Mannino, Marie Schmitt, Georg Guérard, Melanie Müller, Lutz Greig, Gerard Amemiya, Kenjie Peck, Richard Singer, Thomas Doessegger, Lucette |
author_facet | Banholzer, Maria Longauer Wandel, Christoph Barrow, Paul Mannino, Marie Schmitt, Georg Guérard, Melanie Müller, Lutz Greig, Gerard Amemiya, Kenjie Peck, Richard Singer, Thomas Doessegger, Lucette |
author_sort | Banholzer, Maria Longauer |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4960246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-49602462016-08-10 Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update Banholzer, Maria Longauer Wandel, Christoph Barrow, Paul Mannino, Marie Schmitt, Georg Guérard, Melanie Müller, Lutz Greig, Gerard Amemiya, Kenjie Peck, Richard Singer, Thomas Doessegger, Lucette Clin Transl Med Perspective 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. Springer Berlin Heidelberg 2016-07-25 /pmc/articles/PMC4960246/ /pubmed/27455840 http://dx.doi.org/10.1186/s40169-016-0103-8 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Perspective Banholzer, Maria Longauer Wandel, Christoph Barrow, Paul Mannino, Marie Schmitt, Georg Guérard, Melanie Müller, Lutz Greig, Gerard Amemiya, Kenjie Peck, Richard Singer, Thomas Doessegger, Lucette Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update |
title | Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update |
title_full | Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update |
title_fullStr | Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update |
title_full_unstemmed | Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update |
title_short | Clinical trial considerations on male contraception and collection of pregnancy information from female partner: update |
title_sort | clinical trial considerations on male contraception and collection of pregnancy information from female partner: update |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960246/ https://www.ncbi.nlm.nih.gov/pubmed/27455840 http://dx.doi.org/10.1186/s40169-016-0103-8 |
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