The goals of this study are to measure the amount of bulevirtide (BLV) that gets into the blood stream and how long it takes to get rid of it, measure the effect of BLV on bile acids, and evaluate the safety and tolerability of multiple doses of BLV in participants with normal and impaired hepatic (liver) function.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
74
2 mg administered via subcutaneous injections.
10 mg administered via subcutaneous injections.
Orange County Research Center
Lake Forest, California, United States
Clinical Pharmacology of Miami, LLC
Miami, Florida, United States
University of Miami
Miami, Florida, United States
Orlando Clinical Research Center
Orlando, Florida, United States
Pharmacokinetic (PK) Parameter: AUCtau of Bulevirtide (BLV)
AUCtau was defined as the area under the concentration versus time curve (AUC) over the dosing interval at steady state.
Time frame: Day 6: Predose and up to 24 hours postdose
PK Parameter: Cmax,ss of BLV
Cmax,ss was defined as the maximum observed concentration of drug at steady state.
Time frame: Day 6: Predose and up to 24 hours postdose
PK Parameter: AUC0-24h of BLV
AUC0-24h was defined as the partial area under the concentration versus time curve from time zero to time 24 hours.
Time frame: Day 1: Predose and up to 24 hours postdose
PK Parameter: Tmax of BLV
Tmax was defined as the time (observed time point) of Cmax.
Time frame: Days 1 and 6: Predose and up to 24 hours postdose
PK Parameter: Cmax of BLV
Cmax was defined as the maximum observed plasma concentration of drug.
Time frame: Day 1: Predose and up to 24 hours postdose
PK Parameter: t1/2 of BLV
t1/2 was defined as estimate of the terminal elimination half-life of the drug in plasma, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).
Time frame: Day 6: Predose and up to 48 hours postdose
PK Parameter: CLss/F of BLV
CLss/F was defined as the apparent clearance at the steady state (CLss) after administration of the drug: CLss/F = Dose/AUCtau, where "Dose" is the dose of the drug per interval.
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Texas Liver Institute
San Antonio, Texas, United States
Pinnacle Clinical Research LLC
San Antonio, Texas, United States
Time frame: Day 6: Predose and up to 48 hours postdose
PK Parameter: Vss/F of BLV
Vss/F was defined as the apparent steady-state volume of distribution of the drug.
Time frame: Day 6: Predose and up to 48 hours postdose
Pharmacodynamic (PD) Parameter: Ctrough of Total Bile Acids (BA)
Ctrough was defined as the concentration of total BA at the end of the dosing interval.
Time frame: Predose on Days 2, 3, 4, 5, 7, and 8
PD Parameter: Cmax of Total BA
Cmax was defined as the maximum observed concentration of total BA.
Time frame: Days 1 and 6: Predose and up to 24 hours postdose
PD Parameter: AUC0-24h of Total BA
AUC0-24 was defined as the partial area under the concentration versus time curve from time "0" to time "24" hours for total BA.
Time frame: Days 1 and 6: Predose and up to 24 hours postdose
PD Parameter: NetAUC of Total BA
NetAUC was defined as the positive portion of area under the baseline-adjusted biomarker concentration versus time curve over the dosing interval.
Time frame: Days 1 and 6: Predose and up to 24 hours postdose
PD Parameter: Tmax of Total BA
Tmax was defined as the time (observed time point) of Cmax of total BA.
Time frame: Days 1 and 6: Predose and up to 24 hours postdose
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
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 any AEs leading to premature discontinuation of study drug. If the AE onset date is the same as the date of study drug start date then the AE onset time must be on or after the study drug start time. If the AE onset time is missing when the start dates were the same, the AE were considered treatment emergent. An AE was any untoward medical occurrence in a clinical study participant administered a study drug that did not necessarily had a causal relationship with the treatment.
Time frame: First dose date up to Day 6 plus 30 days
Percentage of Participants With Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days. If the relevant baseline laboratory value is missing, any abnormality of at least Grade 1 observed within the time frame specified above will be considered treatment emergent. 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.
Time frame: First dose date up to Day 6 plus 30 days