Severe Hepatic Impairment
Conditions
Brief summary
The primary objective of this study is to characterize the steady state plasma
Detailed description
The primary objective of this study is to characterize the steady state plasma PK of rifaximin (550 mg BID) in subjects with severe hepatic impairment (MELD 19 to 25 and MELD \>25), as well as healthy subjects with normal hepatic function.
Interventions
DRUGRifaximin
Rifaximin 550 MG BID
Sponsors
Bausch Health Americas, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
open-label, repeat-dose, parallel-design study in 12 subjects with severe hepatic impairment and 6 healthy subjects with normal hepatic function.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Hepatically impaired subjects will be ≥18 years of age, have a diagnosis of liver cirrhosis and a MELD score of ≥19 at Screening. Note: At least 6 of the hepatically impaired subjects will have a MELD score of \>25.
Exclusion criteria
* Subject has known allergy to rifaximin, rifampin, or other rifamycins, excipients and/or vehicles used in the formulation, or any other clinically significant allergies. * Subject has participated in an investigational drug or device study within 30 days prior to Day 1 (Baseline). * Subject has any concurrent illness (other than liver cirrhosis), disability or circumstance that may affect the interpretation of clinical data, could cause noncompliance with treatment or visits or otherwise contraindicates participation in this study in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 7 days | Maximum observed plasma concentration (Cmax) of rifaximin and 25-desacetyl rifaximin, if measurable |
| Time of the Maximum Concentration (Tmax) | 7 days | Time of the maximum concentration (Tmax) of rifaximin and 25-desacetyl rifaximin, if measurable |
| Area Under the Plasma Concentration Versus Time Curve (AUC) During the 12-hour Dose Interval | 7 days | Area under the plasma concentration versus time curve (AUC) during the 12-hour dose interval of rifaximin and 25-desacetyl rifaximin, if measurable |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rifaximin Rifaximin 550 mg BID
Rifaximin: Rifaximin 550 MG BID | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Rifaximin |
|---|---|
| Age, Continuous | 45.8 years STANDARD_DEVIATION 6.87 |
| Model for End Stage Liver Disease Score at baseline: 19 to 25 | 4 Participants |
| Model for End Stage Liver Disease Score at baseline: Healthy | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 2 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve (AUC) During the 12-hour Dose Interval
Area under the plasma concentration versus time curve (AUC) during the 12-hour dose interval of rifaximin and 25-desacetyl rifaximin, if measurable
Time frame: 7 days
Population: Participants with Model for End Stage Liver Disease (MELD) of 19 to 25 (N=4) were assessed for pharmacokinetic parameters. There were too few healthy participants (N=1) to assess.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Rifaximin | Area Under the Plasma Concentration Versus Time Curve (AUC) During the 12-hour Dose Interval | rifaximin | 98.7 h*ng/mL | Geometric Coefficient of Variation 107 |
| Rifaximin | Area Under the Plasma Concentration Versus Time Curve (AUC) During the 12-hour Dose Interval | 25-desacetyl rifaximin | 3.04 h*ng/mL | Geometric Coefficient of Variation 85.2 |
Primary
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration (Cmax) of rifaximin and 25-desacetyl rifaximin, if measurable
Time frame: 7 days
Population: Participants with Model for End Stage Liver Disease (MELD) of 19 to 25 (N=4) were assessed for pharmacokinetic parameters. There were too few healthy participants (N=1) to assess.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Rifaximin | Maximum Observed Plasma Concentration (Cmax) | rifaximin | 13.4 ng/mL | Geometric Coefficient of Variation 90 |
| Rifaximin | Maximum Observed Plasma Concentration (Cmax) | 25-desacetyl rifaximin | 0.356 ng/mL | Geometric Coefficient of Variation 87.5 |
Primary
Time of the Maximum Concentration (Tmax)
Time of the maximum concentration (Tmax) of rifaximin and 25-desacetyl rifaximin, if measurable
Time frame: 7 days
Population: Participants with Model for End Stage Liver Disease (MELD) of 19 to 25 (N=4) were assessed for pharmacokinetic parameters. There were too few healthy participants (N=1) to assess.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rifaximin | Time of the Maximum Concentration (Tmax) | rifaximin | 0.688 hours | Standard Deviation 0.688 |
| Rifaximin | Time of the Maximum Concentration (Tmax) | 25-desacetyl rifaximin | 0.625 hours | Standard Deviation 0.75 |