A study to evaluate the effects of various degrees of reduced kidney function on how the study drug (RO7223280) is broken down and eliminated from the body

Phase 1

• Conditions: Bacterial infection; Infections and Infestations

• Registration Number: ISRCTN39200026
• Lead Sponsor: F. Hoffmann-La Roche

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-04-19
• Last Update Posted: 19 December 2023
• Study Completion: 2024-01-29

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Male and female participants aged 18 to 82 years of age inclusive at screening
2. Participants must have a body weight of at least 50 kg and a body mass index (BMI) within the range of 18 to 40 kg/m2 inclusive at screening and admission to the clinic

Criteria for participants with normal renal function only:
1. Participants must be in reasonably good health for their age group as determined by the Investigator
2. Estimated glomerular filtration rate (eGFR) at screening using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation (based on serum creatinine) of =90 mL/min. The stability of renal function will be confirmed by 2 determinations of serum creatinine separated by at least 7 days. Renal function is considered stable if the two serum creatinine values differ by =20%
3. Matched to participants with mild, moderate, or severe renal impairment in sex, age (± 10 years), and BMI (± 15%) at screening

Criteria for participants with renal impairment only:
1. eGFR at screening and admission to the clinic using the CKD-EPI equation (based on serum creatinine) of: For mild renal impairment: =60 to <90 mL/min (Part 1); moderate renal impairment: =30 to <60 mL/min (Part 2); severe renal impairment: <30 mL/min (participants must not be on dialysis and in the opinion of the Investigator will not require dialysis during the study) (Part 3)
2. Stable renal function (Parts 1, 2, and 3). The stability of renal function will be confirmed by two determinations of serum creatinine separated by at least 7 days. Renal function is considered stable if the two serum creatinine values differ by =20%

Criteria for participants with ESRD requiring haemodialysis:
1. Reduced renal function with a clinical diagnosis of ESRD requiring renal replacement therapy
2. Requiring haemodialysis for more than 3 months at the time of the screening visit

Exclusion Criteria

1. History or evidence of any medical conditions potentially altering the absorption, distribution, metabolism, or elimination of RO7223280, except those conditions associated with the primary renal disease
2. History of malignancy within the last year
3. Suffering from an active symptomatic infection (such as influenza, urinary tract infection, or gastrointestinal infections) within 2 weeks prior to treatment administration
4. Evidence of human immunodeficiency virus (HIV) infection and/or positive result for human HIV antibodies
5. Presence of hepatitis B surface antigen or positive hepatitis C antibody test result
6. History of hypersensitivity to any of the excipients in the formulation of RO7223280 or OmnipaqueTM

Criteria for participants with normal renal function only:
1. Significant history or clinical manifestation of renal disorder, as determined by the Investigator
2. History or presence of renal disease or renal injury as indicated by any clinically significant deviations from normal reference ranges in renal function tests, unless approved by the Investigator

Criteria for participants with renal impairment or ESRD requiring haemodialysis only:
1. Nephrotic syndrome (defined as plasma albumin <2 g/dL combined with proteinuria >3 g/day)
2. Participants with renal impairment due to hepatic disease (hepatorenal syndrome)
3. Presence of a renal carcinoma, or an acute renal disease caused by infection or drug toxicity
4. Subjects with a functioning renal transplant or who are active on the transplant waiting list
5. Values outside the normal range for renal and liver function tests that are not consistent with their renal condition, as determined by the Investigator.
6. Blood potassium concentration <3 mmol/L or > 6.5 mmol/L at screening or admission to the clinic
7. Hyponatremia (<120 mmol/L) or hypernatremia (>150 mmol/L) at screening or admission to the clinic
8. Clinically significant liver disease, e.g., hepatitis, cirrhosis, and/or confirmed liver enzymes
9. Haemoglobin concentration <8.5 g/dL at screening or admission to the clinic

Study & Design

• Study Type: Interventional
• Study Design: Not specified