NCT05760300CompletedPhase 1
A Phase 1 Open-Label, Parallel-Design, Multiple-Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Bulevirtide in Participants With Normal and Impaired Renal Function
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 41
- Locations
- 9
- Primary Endpoint
- Pharmacokinetic (PK) Parameter for Bulevirtide (BLV): AUCtau
Study Overview
Brief Summary
The goals of this study are to compare the amount of study drug, bulevirtide (BLV), that gets into the bloodstream and how long it takes for the body to eliminate it, measure the effect of BLV on bile acids, and evaluate the safety and tolerability of multiple doses of BLV in participants with normal or impaired renal (kidney) function.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 79 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •All Individuals:
- •Body mass index (BMI) of at least ≥ 18.0 kg/m^2 and ≤ 40.0 kg/m^2 at screening.
- •No clinically significant abnormalities on electrocardiogram (ECG)
- •No known Liver Disease (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) ≤ 3 x upper limit of normal (ULN) at screening.
- •Individuals with Renal Impairment (RI):
- •Have RI classification at screening that has been unchanged during the 90 days prior to study drug dosing.
- •Estimated Glomerular Filtration Rate (eGFR) must be the following (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Inker 2021)) based on serum creatinine as measured at the screening evaluation:
- •Severe RI (Groups A and B): eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2
- •Moderate RI (Group C): eGFR ≥ 30 to ≤ 59 mL/min/1.73 m^2
- •Mild RI (Group D): eGFR ≥ 60 to ≤ 89 mL/min/1.73 m^2
- •Hemoglobin ≥ 9 g/dL at screening.
- •Individuals with cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, hypothyroidism, osteoporosis, and many others) may be included provided that these diseases/conditions are clinically stable.
- •Matched Control Individuals:
- •Have an eGFR of at least 90 mL/min/1.73 m^2 (using the CKD-EPI equation) based on serum creatinine as measured at screening evaluation.
- •Matched for sex, age (± 10 years), and BMI (± 20%, 18.0 ≤ BMI ≤ 40.0 kg/m^2) with the respective participant in the RI group.
Exclusion Criteria
- •All Individuals:
- •Positive human immunodeficiency virus (HIV) test, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody with detectable HCV viral ribonucleic acid (RNA) at screening.
- •Have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with participant treatment, assessment, or compliance with the protocol.
- •Individuals with RI:
- •Recent history of reception of any blood or blood products or history of major bleeding within 4 weeks of dosing.
- •Positive test for drugs of abuse, including alcohol at screening or admission, with the exception of opioids and tetrahydrocannabinol (THC, marijuana) under prescription and verified by the investigator as for pain management.
- •Received treatment with trimethoprim or cimetidine or tenofovir prodrugs (tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF)) (affects elimination of creatinine) or with competitors of renal tubular excretion (eg, probenecid, chronic high-dose nonsteroidal anti-inflammatory drugs) within 28 days of Day -
- •Received known nephrotoxic drugs (eg, aminoglycosides, amphotericin B, vancomycin, cidofovir, foscarnet, cisplatin, pentamidine, cyclosporine, tacrolimus, herbal remedies (eg, compounds with aristolochic acid)) within 28 days of Day -
- •Individuals requiring or anticipated to require dialysis within 90 days of study entry.
- •Serum albumin concentration <25 g/L.
- •Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated measurements for systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥110 mmHg); current or documented history of repeated clinically significant hypotension or severe episodes of orthostatic hypotension (systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg).
- •Matched Control Individuals:
- •Have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
Arms & Interventions
Group A: BLV 2 mg (Severe RI Group)
Experimental
Participants with severe renal impairment (RI) [estimated glomerular filtration rate (eGFR) ≥ 15 to ≤ 29 mL/min/1.73 m^2] will receive bulevirtide (BLV) 2 mg, administered subcutaneously (SC), once daily (QD), for 6 days.
Intervention: Bulevirtide (BLV) (Drug)
Group A: BLV 2 mg (Matched Control)
Experimental
Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] will receive BLV 2 mg, administered SC, QD, for 6 days.
Intervention: Bulevirtide (BLV) (Drug)
Group B: BLV 10 mg (Severe RI Group)
Experimental
Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] will receive BLV 10 mg, administered SC, QD, for 6 days.
Intervention: Bulevirtide (BLV) (Drug)
Group B: BLV 10 mg (Matched Control)
Experimental
Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] will receive BLV 10 mg, administered SC, QD, for 6 days.
Intervention: Bulevirtide (BLV) (Drug)
Outcomes
Primary Outcomes
Pharmacokinetic (PK) Parameter for Bulevirtide (BLV): AUCtau
Time Frame: Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose
AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state at Day 6.
PK Parameter for BLV: Cmax ss
Time Frame: Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose
Cmax is defined as the maximum observed concentration of drug at steady state at Day 6.
Secondary Outcomes
- PK Parameter for BLV: AUC0-24(Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose)
- PK Parameter for BLV: Cmax(Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose)
- PK Parameter for BLV: Tmax(Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose; Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose)
- PK Parameter for BLV: t1/2(Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose; Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose)
- PK Parameter for BLV: CLss/F(Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose)
- PK Parameter for BLV: Vss/F(Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose)
- Pharmacodynamic (PD) Parameter for Total Bile Acids (BA): Cmax(Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose; Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose)
- PD Parameter for Total BA: AUC0-24(Days 1 and 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose)
- PD Parameter for Total BA: NetAUC(Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose; Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose)
- Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)(Up to 36 days)
- Percentage of Participants Experiencing Laboratory Abnormalities(Up to 36 days)
Investigators
Study Sites (9)
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