Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529
Abstract Background Since nearly half of all pregnancies in the US and worldwide are unintended, there is a critical need for additional contraceptive options for men and women. After a hiatus in non-hormonal male contraceptive development of about half a century, the new chemical entity YCT-529 – a...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-01004-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849342559249235968 |
|---|---|
| author | Nadja Mannowetz Stewart W. McCallum Sharan Sidhu Karen H. Mena Eric P. Ruby Ramiro Castro-Santamaria Emily Dodds Dennis Henderson Gareth Whitaker Heather Wright Sarah Beaudoin Akash Bakshi |
| author_facet | Nadja Mannowetz Stewart W. McCallum Sharan Sidhu Karen H. Mena Eric P. Ruby Ramiro Castro-Santamaria Emily Dodds Dennis Henderson Gareth Whitaker Heather Wright Sarah Beaudoin Akash Bakshi |
| author_sort | Nadja Mannowetz |
| collection | DOAJ |
| description | Abstract Background Since nearly half of all pregnancies in the US and worldwide are unintended, there is a critical need for additional contraceptive options for men and women. After a hiatus in non-hormonal male contraceptive development of about half a century, the new chemical entity YCT-529 – a retinoic acid receptor-α antagonist - is being developed as a non-hormonal oral male contraceptive to decrease sperm count by impairing retinoic acid signaling in the testes. Methods Here, we report the results of the first in human Phase 1a clinical trial with YCT-529 to assess its safety, tolerability, pharmacokinetics and pharmacodynamics, and its potential effects on heart rate, inflammatory biomarkers, sexual desire and mood. Sixteen male volunteers were enrolled to receive single oral doses of 10, 30, 90 or 180 mg of YCT-529 in the fasted state. Volunteers also received 30 mg in the fed state to study the effect of food on the pharmacokinetics of YCT-529. Results Single doses of up to 180 mg of YCT-529 had no effects on heart rate, hormone (follicle-stimulating hormone, luteinizing hormone, and testosterone), sex hormone-binding globulin or inflammatory biomarker levels, sexual desire or mood. Further, there was no clear food effect on the pharmacokinetics of YCT-529. Conclusions Overall, YCT-529 was well tolerated in this single ascending dose study (ClinicalTrials.gov registration: NCT06094283), which is a substantial requirement in contraceptive development. |
| format | Article |
| id | doaj-art-e0ef6fd0fff04c53b574130c4ad2cba9 |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-e0ef6fd0fff04c53b574130c4ad2cba92025-08-20T03:43:21ZengNature PortfolioCommunications Medicine2730-664X2025-07-01511910.1038/s43856-025-01004-4Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529Nadja Mannowetz0Stewart W. McCallum1Sharan Sidhu2Karen H. Mena3Eric P. Ruby4Ramiro Castro-Santamaria5Emily Dodds6Dennis Henderson7Gareth Whitaker8Heather Wright9Sarah Beaudoin10Akash Bakshi11YourChoice TherapeuticsYourChoice TherapeuticsQuotient SciencesYourChoice TherapeuticsYourChoice TherapeuticsIncyteQuotient SciencesQuotient SciencesQuotient SciencesQuotient SciencesQuotient SciencesYourChoice TherapeuticsAbstract Background Since nearly half of all pregnancies in the US and worldwide are unintended, there is a critical need for additional contraceptive options for men and women. After a hiatus in non-hormonal male contraceptive development of about half a century, the new chemical entity YCT-529 – a retinoic acid receptor-α antagonist - is being developed as a non-hormonal oral male contraceptive to decrease sperm count by impairing retinoic acid signaling in the testes. Methods Here, we report the results of the first in human Phase 1a clinical trial with YCT-529 to assess its safety, tolerability, pharmacokinetics and pharmacodynamics, and its potential effects on heart rate, inflammatory biomarkers, sexual desire and mood. Sixteen male volunteers were enrolled to receive single oral doses of 10, 30, 90 or 180 mg of YCT-529 in the fasted state. Volunteers also received 30 mg in the fed state to study the effect of food on the pharmacokinetics of YCT-529. Results Single doses of up to 180 mg of YCT-529 had no effects on heart rate, hormone (follicle-stimulating hormone, luteinizing hormone, and testosterone), sex hormone-binding globulin or inflammatory biomarker levels, sexual desire or mood. Further, there was no clear food effect on the pharmacokinetics of YCT-529. Conclusions Overall, YCT-529 was well tolerated in this single ascending dose study (ClinicalTrials.gov registration: NCT06094283), which is a substantial requirement in contraceptive development.https://doi.org/10.1038/s43856-025-01004-4 |
| spellingShingle | Nadja Mannowetz Stewart W. McCallum Sharan Sidhu Karen H. Mena Eric P. Ruby Ramiro Castro-Santamaria Emily Dodds Dennis Henderson Gareth Whitaker Heather Wright Sarah Beaudoin Akash Bakshi Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529 Communications Medicine |
| title | Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529 |
| title_full | Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529 |
| title_fullStr | Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529 |
| title_full_unstemmed | Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529 |
| title_short | Safety and pharmacokinetics of the non-hormonal male contraceptive YCT-529 |
| title_sort | safety and pharmacokinetics of the non hormonal male contraceptive yct 529 |
| url | https://doi.org/10.1038/s43856-025-01004-4 |
| work_keys_str_mv | AT nadjamannowetz safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT stewartwmccallum safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT sharansidhu safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT karenhmena safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT ericpruby safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT ramirocastrosantamaria safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT emilydodds safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT dennishenderson safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT garethwhitaker safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT heatherwright safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT sarahbeaudoin safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 AT akashbakshi safetyandpharmacokineticsofthenonhormonalmalecontraceptiveyct529 |