Pharmacokinetics of giredestrant in females with impaired hepatic functions Not Applicable
Conditions
Interventions
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
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
Female
Inclusion criteria
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
Exclusion criteria
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 (AUC0-8) 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
United States of America
Outcome results
None listed