A study to evaluate the processing by the body of giredestrant in female participants of non-childbearing potential with impaired liver functions

Phase 1

• Conditions: Pharmacokinetics of giredestrant in females with impaired hepatic functions; Not Applicable

• Registration Number: ISRCTN14030004
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-10-10
• Last Update Posted: 28 November 2022
• Study Completion: 2024-12-02

Recruitment & Eligibility

• Status: Ongoing
• Sex: Female
• Target Recruitment: 28

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified