Bioavailability and ADME study of GDC-9545 in healthy females (204283)
Research type
Research Study
Full title
A Phase I, Single Center, Open-Label, Partially Randomized, Two Part Study To Investigate The Absorption, Metabolism, And Excretion Of [14C]-GDC-9545 Following A Single Oral Dose (Part 1) And To Evaluate The Absolute Bioavailability Of Oral Capsule Formulations Of GDC-9545 F12 And F18 And The Relative Bioavailability Of F18 Compared To F12 (Part 2) In Healthy Female Subjects Of Non-Childbearing Potential
IRAS ID
290377
Contact name
Eric Olson
Contact email
Sponsor organisation
Genentech, Inc.
Eudract number
2020-004650-29
Duration of Study in the UK
0 years, 1 months, 29 days
Research summary
Research Summary
The Sponsor is developing the test medicine, GDC-9545, for the potential treatment of breast cancer. A common type of breast cancer is oestrogen receptor breast cancer, currently treated using a variety of medicines, but often the cancer returns or the medicine stops working. Thus, new treatments are required for this type of breast cancer.
Part 1 only involves radiolabelling (labelling the test medicine with radioactive 14C) which is used to locate the test medicine within the body.
The study will try to assess the how much radioactivity can be recovered from the urine and faeces (mass balance) and the routes of elimination. It will also try to determine how much of the test medicine enters the bloodstream over time (pharmacokinetics). It will try to identify which metabolites (breakdown products) are generated along with measuring the amount of oral test medicine that enters the bloodstream (absolute bioavailability) and compare two forms of the test medicine (relative oral bioavailability). Safety and tolerability will also be assessed.
The study will consist of two parts involving up to 16 healthy female volunteers of non-childbearing potential. In Part 1, up to 6 volunteers will receive a single oral dose of radiolabelled test medicine as a capsule. Blood, urine and faeces samples will be collected until at least 480 hours post-dose. Volunteers may be required to return to the clinical unit on up to three occasions for sample collection.
Part 2 consists of three periods, 10 volunteers will be enrolled to receive a single dose of the test medicine on three occasions. The test medicine will be administered as a capsule on two occasions, and intravenously on one occasion. There will be a minimum washout period of 10 days between each administration of the test medicine. There will be a follow-up call 13 – 15 days post-final dose.
Summary of Results
This study was done to find out what happens to a new medicine inside women’s bodies. People in this study were given the study medicine, giredestrant, in different forms. This study included 16 healthy women in one country. One of the findings was that giredestrant is excreted (removed from the body) mainly in the feces and very little is removed in urine. A comparison of two different capsule formulations of giredestrant showed both deliver approximately the same amount of medicine in the body. This was about 60% of the amount compared to when giredestrant was given intravenously. There were no serious side effects in this study.
A more detailed lay summary of results has been provided for participants at the following link: https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Furl6570.hra.nhs.uk%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbSgv9uUS1wsd00iFWSZyptH89w1tcscJeKmImtXTgMdp2ltoze1BZTF3jHs57JGrX52-2FHxUfN-2FHzK-2Bo-2B4f8o8QhzarGAHkv-2Fvx3HnjYs-2Bnpl-2Fp9XA8XC0FE3nfmx43xGj1NiYyobs6SrKOUtjls7rBILcnvaEMSY-2FAaNR5Q6LXkueZ_U_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YKta1dNAahT88Nt-2Fz0Ybvmme5al5bAvYz4PBlStNUvj5KJ5-2BoqeprPHh4vAutLDN-2Byyc-2FVc9ViTp-2F02cG03UlrTKJkARxZubAXwsmm6PRqco0xdP0TRYayAdcF7Uz1W8Ll5DSP-2BwSSVX0qFzgR-2Ft2VHA6tjjQ2psSxM7VH9F9blYQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C0903c46e2e4a4bdd746908da2458bcd0%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637862260783511813%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=oTKh7MifJyNF5mGiir%2Fmtk7iXajCqDOa01czv48cQUU%3D&reserved=0REC name
HSC REC A
REC reference
20/NI/0159
Date of REC Opinion
11 Dec 2020
REC opinion
Further Information Favourable Opinion