A study to evaluate the processing by the body of giredestrant in female participants of non-childbearing potential with impaired liver functions
| ISRCTN | ISRCTN14030004 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14030004 |
| Secondary identifying numbers | GP44228 |
- Submission date
- 07/10/2022
- Registration date
- 10/10/2022
- Last edited
- 17/11/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
Breast cancer is a disease in which cells in the breast grow out of control. It is the most common cancer diagnosed in women, and accounts for approximately 15% of all cancer deaths. Most breast cancers grow with the help of the female hormone receptors called estrogen receptors (ER). A receptor is a part of a cell that attaches to a specific substance and this attachment causes changes, such as the release/making of a protein. Hence, treatments of breast cancer are mainly centered around therapies that modify these receptors (endocrine therapies). However, in many participants the cancer comes back after treatment (called relapse), or they experience reduction in the effectiveness of medication (resistance) over a period of time. Giredestrant is a drug being developed for the treatment of breast cancer. Health authorities have not yet approved giredestrant for the treatment of breast cancer or any other disease. The main aim of the study is to measure how much of the drug gets into the blood stream and how long it takes the body to get rid of it when given to female participants who are unable to become pregnant, with normal liver function or differing levels of liver problems (impairment). In addition, the safety and tolerability of the giredestrant and any side effects that may occur also will be evaluated.
Who can participate?
Female participants of non-childbearing potential between 18 and 75 years of age with normal liver function or differing levels of liver impairment
What does the study involve?
Participants will need to be a part of this study for about 4 weeks. The study will include the following parts:
1. A screening part of up to 28 days to check the eligibility of participants to take part in the study
2. A dosing/confinement part of up to 9-12 days depending on whether the participants have normal or impaired liver function where participants will receive single dose of giredestrant by mouth on Day 1 after an overnight fast of at least 8 hours. Participants will be required to fast for at least 4 hours after taking giredestrant.
3. A follow-up part during which participants will receive a follow-up telephone call 28 (±2) days following drug administration.
What are the possible benefits and risks of participating?
Participant’s health may or may not improve in this study, but the information that is learned may help other people who have breast cancer in the future. Participants will receive monetary compensation for taking part in the study.
Participants may have side effects from giredestrant, or procedures used in this study. These can be mild to severe and even life threatening, and they can vary from person to person. There may be side effects that are not known at this time. The potential side effects associated with giredestrant, and other procedures are listed below:
Risks associated with Giredestrant:
● Very Common Side Effects: Pain or stiffness in joints (arthralgia), loose stools (diarrhea), tiredness (fatigue), muscle or bone pain (musculoskeletal pain), nausea, possible liver damage (abnormal liver tests)
● Common Side Effects: Slow heart rate, dizziness, hot flush, vomiting, headache
● Potential Side Effects: Blood clots, damage to the kidneys, changes to female reproductive organs, including fluid-filled lump in the ovary (ovarian cysts) and decreased uterine weight, female infertility; menopausal symptoms
2. Risk associated with study procedures:
● Blood Sampling: Drawing blood can cause pain, bruising, or infection where the needle is inserted. Some people experience dizziness, fainting, or upset stomach when their blood is drawn
● Electrocardiograms (ECG): ECG patches may cause a skin reaction such as redness or itching. Participants may also experience localized skin discomforts and/or hair loss associated with the placement of ECG leads.
There may be a risk in exposing an unborn child to study drug, and all risks are not known at this time. Participants who can become pregnant cannot take part in this study.
Where is the study run from?
F. Hoffmann-La Roche Ltd (USA)
When is the study starting and how long is it expected to run for?
June 2022 to December 2024
Who is funding the study?
F. Hoffmann-La Roche Ltd (USA)
Who is the main contact?
global-roche-genentech-trials@gene.com
Contact information
Scientific
1 DNA Way
South San Francisco
94080
United States of America
| Phone | +1 (0)888 662 6728 |
|---|---|
| global-roche-genentech-trials@gene.com |
Study information
| Study design | Open-label multicenter parallel-cohort single-dose phase I study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | No participant information sheet available |
| Scientific title | A phase I, open-label, single-dose, parallel-cohort study to evaluate the pharmacokinetics of giredestrant in female subjects of non-childbearing potential with impaired hepatic functions |
| Study objectives | The aim of the study is to evaluate pharmacokinetics (PK) and safety of a single oral dose of giredestrant in female participants of non-childbearing potential with mild, moderate, and severe hepatic impairment. |
| Ethics approval(s) | Approved 24/082022, Salus IRB (2111 W. Braker Lane, Suite 100, Austin, Texas 78758, USA; +1 512-380-1244; salus@salusirb.com), ref: none provided |
| Health condition(s) or problem(s) studied | Pharmacokinetics of giredestrant in females with impaired hepatic functions |
| Intervention | Giredestrant 30 milligrams (mg): Participants with normal hepatic function and mild, moderate and severe hepatic impairment will receive a single dose of giredestrant, 30 mg, orally on Day 1, after a fast of 8 hours. Participants will be required to fast for up to 4 hours postdose. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Giredestrant |
| Primary outcome measure | 1. Maximum Observed Concentration (Cmax) of Giredestrant Measured Using Plasma Samples Taken at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 2. Time to Maximum Observed Concentration (tmax) of Giredestrant Measured Using Plasma Samples Taken at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 3. Area Under the Concentration-time Curve from Hour 0 to the Last Measurable Concentration (AUC0-t) of Giredestrant Measured Using Plasma Samples Taken at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 4. Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-∞) of Giredestrant Measured Using Plasma Samples Taken at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 5. Percentage of AUC Due to Extrapolation from the Last Measurable Concentration to Infinity (%AUCextrap) of Giredestrant Measured Using Plasma Samples Taken at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 6. Apparent Terminal Elimination Half-life (t1/2) of Giredestrant Measured Using Plasma Samples Taken at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 7. Apparent Total Clearance (CL/F) of Giredestrant Measured Using Blood Samples at Multiple Timepoints at Multiple Timepoints from Day 1 up to Day 12 or Early Termination Visit (Day 12) 8. Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Giredestrant Measured Using Plasma Samples at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 9. Fraction of Unbound Giredestrant (fu) Measured Using Plasma Samples at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 10. Unbound Maximum Observed Concentration (Cmax,u) of Giredestrant Measured Using Plasma Samples at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 11. Unbound Area Under the Concentration-time Curve of Giredestrant at Multiple Timepoints from Hour 0 to the Last Measurable Concentration (AUC0-t,u) Measured Using Plasma Samples from Day 1 up to Day 12 or Early Termination 12. Unbound Area Under the Concentration-time Curve Extrapolated to Infinity (AUC0-∞,u) of Giredestrant Measured Using Plasma Samples at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 13. Unbound Apparent Total Clearance (CLu/F) of Giredestrant Measured Using Plasma Samples at Multiple Timepoints from Day 1 up to Day 12 or Early Termination 14. Unbound Apparent Volume of Distribution During the Terminal Elimination Phase (Vz,u/F) of Giredestrant Measured Using Plasma Samples at Multiple Timepoints from Day 1 up to Day 12 or Early Termination |
| Secondary outcome measures | 1. Number of Participants with Adverse Events (AEs) from Screening to End of Study (Approximately 2.5 years) 2. Number of Participants with Severity of AEs Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) from Screening to End of Study (Approximately 2.5 years) |
| Overall study start date | 29/06/2022 |
| Completion date | 02/12/2024 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 75 Years |
| Sex | Female |
| Target number of participants | 28 |
| Key inclusion criteria | 1. Females between 18 and 75 years of age, inclusive, of non-childbearing potential including non-pregnant, non-lactating, and postmenopausal 2. Females with body weight ≥45 kilograms (kg) and body mass index (BMI) ranging from 18.5 to 40 kilogram per meter square (kg/m²), inclusive, at Screening 3. In good health (except for additional inclusion criteria specific to hepatic impaired participants) 4. Clinical laboratory evaluations within the reference range for the test laboratory, unless deemed not clinically significant by the investigator. It is acceptable to have clinical laboratory values outside the reference range, consistent with participants hepatic condition 5. Negative hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody) and negative human immunodeficiency virus (HIV) antibody screens Additional inclusion criteria for participants with normal hepatic function: 6. Matched to participants with mild, moderate, or severe hepatic impairment in age (±10 years) and body weight (±15 %) 7. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and bilirubin must be less than or equal to the upper limit of normal (ULN) 8. Estimated creatinine clearance ≥60 millileter per minute (mL/min) at Screening Additional inclusion criteria for participants with hepatic impairment only: 9. Considered to have mild, moderate, or severe hepatic impairment and has been clinically stable for at least 1 month prior to Screening 10. Chronic (>6 months), stable (no acute episodes of illness within the previous 1 month prior to Screening due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology. Participants must also remain stable throughout the Screening period 11. Stable medication regimen for at least 1 month prior to Check-in (Day -1) 12. Estimated creatinine clearance ≥55 mL/min at Screening |
| Key exclusion criteria | 1. History of allergy to giredestrant or any of its excipients 2. History of stomach or intestinal surgery (including cholecystectomy) or resection that would potentially alter absorption and/or excretion of orally administered drugs 3. Malabsorption syndrome or other conditions that would interfere with enteral absorption 4. Absolute neutrophil count <1.3 × 10^9/L (1300/μL) at Screening 5. History of active or latent tuberculosis (TB), regardless of treatment history, or positive QuantiFERON® TB Gold test 6. The use of poppy seed-containing foods or beverages within 7 days prior to Check-in (Day -1), unless deemed acceptable by the investigator 7. The use of alcohol-, grapefruit-, or caffeine-containing foods or beverages within 72 hours prior to Check-in (Day -1), unless deemed acceptable by the investigator 8. Poor peripheral venous access 9. Female participant having a history of any malignancy, within 5 years prior to Screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer 10. Evidence of infection with or positive test result for severe acute respiratory syndrome coronavirus 2 Additional exclusion criteria for participants with normal hepatic function: 11. Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, GI neurological, or psychiatric disorder (as determined by the investigator) 12. Regular alcohol consumption >14 units per week (1 unit = ½ pint beer or 25 mL shot of 40% spirit; 1.5 to 2 units = 125 mL glass of wine, depending on type) within 6 months prior to Screening Additional exclusion criteria for participants with hepatic impairment only: 13. Minimal smoking (limit of less than 10 cigarettes/day) in hepatic impaired participants may be allowed at the discretion of the investigator and in consultation with the Sponsor and Medical Monitor. Participants will not be permitted to smoke within 2 hours prior to dose or 4 hours postdose on Day 1 14. Any evidence of progressive liver disease that has worsened or is worsening, as determined by the investigator, within 1 month prior to Screening 15. Demonstrated evidence of hepatorenal syndrome 16. Ascites requiring paracentesis (within 3 months prior to Check-in [Day -1]) or other intervention, with the exception of diuretics 17. Treatment for GI bleeding within 3 months prior to Check-in (Day -1) 18. Prescription of additional medication for hepatic encephalopathy within the 12 months (6 months for severe hepatic impairment) prior to Check-in (Day -1), unless deemed acceptable by the investigator 19. Total bilirubin levels >6 mg/dL. Levels above 6 mg/dL may be allowed at the discretion of the investigator, in consultation with the Sponsor and Medical Monitor 20. Hepatic encephalopathy Grade 2 or above |
| Date of first enrolment | 15/10/2022 |
| Date of final enrolment | 24/10/2024 |
Locations
Countries of recruitment
- United States of America
Study participating centres
78215
United States of America
32809
United States of America
33014
United States of America
92377
United States of America
Sponsor information
Industry
1 DNA Way
South San Francisco
94080
United States of America
| Phone | +1 (0)888 662 6728 |
|---|---|
| global-roche-genentech-trials@gene.com | |
| Website | https://www.roche.com/about_roche/roche_worldwide.htm |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 02/12/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to participant-level data not being a regulatory requirement. |
Editorial Notes
17/11/2022: Clinical Pharmacology of Miami and Inland Empire Clinical Trials were added to the trial participating centres.
10/10/2022: Trial's existence confirmed by Salus IRB
