Hepatitis C Virus
Conditions
Keywords
ribavirin, pharmacokinetics, Hepatitis C virus
Brief summary
The purpose of this study is to determine if concentration-controlled ribavirin dosing can achieve a targeted level of plasma exposures and if it appears safe and effective compared with standard weight-based ribavirin dosing. Forty, previously treatment-naive participants with genotype 1 disease will be randomized to receive concentration-guided or standard weight-based ribavirin. Peginterferon alfa 2a,ribavirin, and telaprevir will be provided through the study.
Interventions
DRUGribavirin
Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Colorado, Denver
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chronic HCV-infected men and women * 18-70 years * HCV genotype 1 * Deemed ready for HCV treatment by hepatology provider and patient * Allowed medications: all those not specifically listed in the
Exclusion criteria
below including medications for peginterferon / ribavirin - related adverse effects: acetaminophen, ibuprofen, diphenhydramine, selective serotonin reuptake inhibitors, darbepoeitin, erythropoietin, GCSF
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ribavirin AUC-12 Variability | steady state (~weeks 9-10) | Demonstrate that concentration-controlled ribavirin dosing can achieve a targeted level of plasma exposure with reduced variability in the steady-state area-under-the-concentration-time curve (AUC0-12) compared with standard weight-based ribavirin dosing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Absolute Hemoglobin Declines | from baseline through end of treatment, up to 48 weeks | — |
| Sustained Virologic Response (i.e., Cure) | assessed 12 weeks after stopping treatment | Compare proportions with SVR in standard weight-based vs. concentration-guided ribavirin dosing groups. Number of participants with sustained virologic response is reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Weight-Based Ribavirin Dosing 1000 mg daily in patients weighing \<75 kg and 1200 mg daily in patients weighing ≥ 75 kg
ribavirin: Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12 | 17 |
| Concentration-Controlled Ribavirin Dosing Dose adjusted based on first dose AUC0-12
ribavirin: Randomization to standard weight based ribavirin dosing (1000 or 1200 mg daily) or concentration-guided dosing based on first dose AUC0-12 | 18 |
| Total | 35 |
Baseline characteristics
| Characteristic | Standard Weight-Based Ribavirin Dosing | Total | Concentration-Controlled Ribavirin Dosing |
|---|---|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 10.2 | 50.3 years STANDARD_DEVIATION 8.8 | 53.4 years STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 8 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 27 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 30 Participants | 15 Participants |
| Region of Enrollment United States | 17 participants | 35 participants | 18 participants |
| Sex: Female, Male Female | 6 Participants | 13 Participants | 7 Participants |
| Sex: Female, Male Male | 11 Participants | 22 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 18 |
| other Total, other adverse events | 14 / 17 | 12 / 18 |
| serious Total, serious adverse events | 4 / 17 | 7 / 18 |
Outcome results
Primary
Ribavirin AUC-12 Variability
Demonstrate that concentration-controlled ribavirin dosing can achieve a targeted level of plasma exposure with reduced variability in the steady-state area-under-the-concentration-time curve (AUC0-12) compared with standard weight-based ribavirin dosing
Time frame: steady state (~weeks 9-10)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Weight-Based Ribavirin Dosing | Ribavirin AUC-12 Variability | 34425 ng*hr/mL | Standard Deviation 10046 |
| Concentration-Controlled Ribavirin Dosing | Ribavirin AUC-12 Variability | 40903 ng*hr/mL | Standard Deviation 10953 |
Secondary
Safety - Absolute Hemoglobin Declines
Time frame: from baseline through end of treatment, up to 48 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Standard Weight-Based Ribavirin Dosing | Safety - Absolute Hemoglobin Declines | 2.6 g/dL | Standard Deviation 1.9 |
| Concentration-Controlled Ribavirin Dosing | Safety - Absolute Hemoglobin Declines | 3.6 g/dL | Standard Deviation 1.2 |
Secondary
Sustained Virologic Response (i.e., Cure)
Compare proportions with SVR in standard weight-based vs. concentration-guided ribavirin dosing groups. Number of participants with sustained virologic response is reported.
Time frame: assessed 12 weeks after stopping treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard Weight-Based Ribavirin Dosing | Sustained Virologic Response (i.e., Cure) | 8 Participants |
| Concentration-Controlled Ribavirin Dosing | Sustained Virologic Response (i.e., Cure) | 12 Participants |