A Multiple-Dose Study of Bulevirtide in Participants With... | NCT05760300

ID	Type	Description	Link
2022-502054-13-00	Other Identifier	European Medicines Agency

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	Drug: Bulevirtide (BLV)
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.	Drug: Bulevirtide (BLV)
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.	Drug: Bulevirtide (BLV)
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.	Drug: Bulevirtide (BLV)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bulevirtide (BLV)	Drug	Administered via subcutaneous (SC) injections	Group A: BLV 2 mg (Matched Control) Group A: BLV 2 mg (Severe RI Group) Group B: BLV 10 mg (Matched Control)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Pharmacokinetic (PK) Parameter for Bulevirtide (BLV): AUCtau	AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state at Day 6.	Day 6: 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 ss	Cmax is defined as the maximum observed concentration of drug at steady state at Day 6.	Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

Secondary Outcomes

Measure	Description	Time Frame
PK Parameter for BLV: AUC0-24	AUC0-24 is defined as the concentration of drug over time between time 0 hour and time 24 hours.	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

Eligibility Module

Eligibility Criteria

Key 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.

Key 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 -1.
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 -1.
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

Name	Affiliation	Role
Gilead Study Director	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Velocity Clinical Research, New Smyrna Beach		Edgewater	Florida	32132	United States
Clinical Pharmacology of Miami, LLC

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
	Background	Yehong Wang, Renee-Claude Mercier, Wildaliz Nieves, David Pan, Carrie Nielson, SteveTseng, Xu Zhang, Ann Qin, Parag Kumar. Pharmacokinetics, Pharmacodynamics, and Safety of Bulevirtide 2 mg Once Daily for 6 Days in Participants with Severe Renal Impairment and in Matched Control Participants with Normal Renal Function. The Liver Meeting, American Association for the Study of Liver Diseases; November 15-19, 2024; San Diego, CA. Abstract #1194.
	Background	Yehong Wang, Renee-Claude Mercier, Wildaliz Nieves, Carolina Machado, Steve Tseng, Yuejiao Jiang, Ann Qin, Teckla Akinyi, Parag Kumar, WED-313 Pharmacokinetics, pharmacodynamics, and safety of bulevirtide 10 mg once daily for 6 days in participants with severe renal impairment and in matched control participants with normal renal function, Journal of Hepatology, Volume 82, Supplement 1, 2025, Page S824 (https://doi.org/10.1016/S0168-8278(25)02119-1).

Label	URL
Gilead Clinical Trials Website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe renal impairment (RI) [estimated glomerular filtration rate (eGFR) ≥ 15 to ≤ 29 mL/min/1.73 m^2] received bulevirtide (BLV) 2 mg, administered subcutaneously (SC), once daily (QD), for 6 days.
FG001	Group A: BLV 2 mg (Matched Control)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 2, 2023	Jul 8, 2025

Arm/Group Information

ID	Title	Description
BG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
BG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
BG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
BG003	Group B: BLV 10 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG00110 BG00211 BG00310 BG00441

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00059± 15.1 BG00155± 10.6 BG00263± 11.1 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Between 18 and 65 years

Title	Measurements
	BG0006 BG0019 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004 BG0014 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0007 BG0018 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00010 BG00110 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Pharmacokinetic (PK) Parameter for Bulevirtide (BLV): AUCtau

AUCtau is defined as the area under the concentration versus time curve over the dosing interval at steady state at Day 6.

The plasma PK Analysis Set included all enrolled participants who received at least 1 dose of BLV and had at least 1 measurable plasma PK concentration data reported by PK laboratory for the respective analyte. Participants in the PK Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

hours(h)*nanograms per milliliter(ng/mL)

Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.

Units	Counts
Participants	OG0006 OG0016 OG00210 OG003

Title

Denominators

Categories

Title	Measurements
	OG00094.6± 29.8 OG001112± 32.6 OG0021880± 642 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Geometric Least-squares Mean Ratio	84.5			2-Sided	90	60.1	119			Parametric (normal theory) analysis of covariance (ANOVA) model appropriate for a parallel design with renal function group as a fixed effect was fitted to the natural log-transformed values of the multiple dose PK parameter under evaluation.		Other
OG002 OG003

Primary

PK Parameter for BLV: Cmax ss

Cmax is defined as the maximum observed concentration of drug at steady state at Day 6.

Participants in the PK Analysis Set with available data were analyzed

Posted

Mean

Standard Deviation

ng/mL

Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.

Secondary

PK Parameter for BLV: AUC0-24

AUC0-24 is defined as the concentration of drug over time between time 0 hour and time 24 hours.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.

Secondary

PK Parameter for BLV: Cmax

Cmax is defined as the maximum observed concentration of drug.

Participants in the PK Analysis Set were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Day 1: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.

Secondary

PK Parameter for BLV: Tmax

Tmax is defined as the time (observed time point) of Cmax.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Median

Full Range

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

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)

Secondary

PK Parameter for BLV: t1/2

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Median

Full Range

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)

Secondary

PK Parameter for BLV: CLss/F

CLss/F is defined as the apparent clearance at steady state at Day 6. CLss/F = Dose/AUCtau, where "Dose" is the dose of the drug per interval.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

milliliters per hour (mL/h)

Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)

Secondary

PK Parameter for BLV: Vss/F

Vss/F is defined as the apparent volume of distribution at steady state at Day 6.

Participants in the PK Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

Day 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, 24, and 48 hours postdose

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.
OG003	Group B: BLV 10 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.

Secondary

Pharmacodynamic (PD) Parameter for Total Bile Acids (BA): Cmax

The PD effect of BLV was evaluated on plasma BA in participants with RI compared to matched control participants with normal renal function. Cmax is defined as the maximum observed concentration of total BA. The plasma bile acid panel includes 15 individual bile acids, and total BA is the sum of these 15 components.

The plasma PD Biomarker Analysis Set included all enrolled participants who received at least 1 dose of study drug BLV and had at least 1 measurable plasma PD concentration value reported for each respective analyte. Participants in the PD Biomarker Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

micromoles per liter (µmol/L)

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002

Secondary

PD Parameter for Total BA: AUC0-24

The PD effect of BLV was evaluated on plasma BA in participants with RI compared to matched control participants with normal renal function. AUC0-24 is defined as the concentration of total BA over time between time 0 hour and time 24 hours. The plasma bile acid panel includes 15 individual bile acids, and total BA is the sum of these 15 components.

Participants in the PD Biomarker Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

h*µmol/L

Days 1 and 6: Predose (≤ 30 minutes before dose), 0.5, 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours postdose

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.

Secondary

PD Parameter for Total BA: NetAUC

The PD effect of BLV was evaluated on plasma BA in participants with RI compared to matched control participants with normal renal function. NetAUC is defined as positive portion of area under the baseline-adjusted biomarker concentration versus time curve over the dosing interval. The plasma bile acid panel includes 15 individual bile acids, and total BA is the sum of these 15 components.

Participants in the PD Biomarker Analysis Set with available data were analyzed.

Posted

Mean

Standard Deviation

h*µmol/L

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.

Secondary

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug and/or if the AE onset date was the same as the date of study drug start date then the AE onset time must have been on or after the study drug start time. If the AE onset time was missing when the start dates was the same, the AE was considered treatment emergent.and/or any AEs leading to premature discontinuation of study drug.

The Safety Analysis Set included all enrolled participants who received at least 1 dose of study drug BLV.

Posted

Number

percentage of participants

Up to 36 days

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)

Secondary

Percentage of Participants Experiencing Laboratory Abnormalities

A treatment-emergent laboratory abnormality was any value that was outside the reference range at any time post baseline up to and including the date of last study drug dose plus 30 days. Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening; Grade 5: Death. Participants with at least a 1 grade increased from baseline for an individual laboratory test where the maximum post baseline laboratory abnormality was grade 1 or higher and grade 3 or higher were reported. The maximum post baseline toxicity grade across all tests for an individual participant was used in analysis.

Participants in the Safety Analysis Set were analyzed.

Posted

Number

percentage of participants

Up to 36 days

ID	Title	Description
OG000	Group A: BLV 2 mg (Severe RI Group)	PParticipants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.
OG002	Group B: BLV 10 mg (Severe RI Group)

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group A: BLV 2 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.	10	0	10	4	10
EG001	Group A: BLV 2 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 2 mg, administered SC, QD, for 6 days.	10	0	10	2	10
EG002	Group B: BLV 10 mg (Severe RI Group)	Participants with severe RI [eGFR ≥ 15 to ≤ 29 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.	11	1	11	2	11
EG003	Group B: BLV 10 mg (Matched Control)	Participants with normal renal function (matched control group) [eGFR ≥ 90 mL/min/1.73 m^2] received BLV 10 mg, administered SC, QD, for 6 days.	10	0	10	3	10

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Eosinophilia	Blood and lymphatic system disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG0030 affected10 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected10 at risk EG0021 affected11 at risk EG003
Vessel puncture site haemorrhage	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG003
Lipase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected10 at risk EG0020 affected11 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected10 at risk EG0021 affected11 at risk EG003
Headache	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 affected10 at risk EG0011 affected10 at risk EG0021 affected11 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 affected10 at risk EG0010 affected10 at risk EG0020 affected11 at risk EG003