Trial Outcomes & Findings for Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection (NCT NCT01097395)
NCT ID: NCT01097395
Last Updated: 2021-09-16
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
35 participants
Primary outcome timeframe
steady state (~weeks 9-10)
Results posted on
2021-09-16
Participant Flow
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
18
|
|
Overall Study
COMPLETED
|
14
|
14
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Concentration-Controlled Ribavirin for the Treatment of Patients With Chronic Hepatitis C Virus Infection
Baseline characteristics by cohort
| Measure |
Standard Weight-Based Ribavirin Dosing
n=17 Participants
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
|
Concentration-Controlled Ribavirin Dosing
n=18 Participants
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
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
47.1 years
STANDARD_DEVIATION 10.2 • n=5 Participants
|
53.4 years
STANDARD_DEVIATION 5.9 • n=7 Participants
|
50.3 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
18 participants
n=7 Participants
|
35 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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
Outcome measures
| Measure |
Standard Weight-Based Ribavirin Dosing
n=17 Participants
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
|
Concentration-Controlled Ribavirin Dosing
n=18 Participants
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
|
|---|---|---|
|
Ribavirin AUC-12 Variability
|
34425 ng*hr/mL
Standard Deviation 10046
|
40903 ng*hr/mL
Standard Deviation 10953
|
SECONDARY outcome
Timeframe: from baseline through end of treatment, up to 48 weeksOutcome measures
| Measure |
Standard Weight-Based Ribavirin Dosing
n=17 Participants
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
|
Concentration-Controlled Ribavirin Dosing
n=18 Participants
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
|
|---|---|---|
|
Safety - Absolute Hemoglobin Declines
|
2.6 g/dL
Standard Deviation 1.9
|
3.6 g/dL
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: assessed 12 weeks after stopping treatmentCompare proportions with SVR in standard weight-based vs. concentration-guided ribavirin dosing groups. Number of participants with sustained virologic response is reported.
Outcome measures
| Measure |
Standard Weight-Based Ribavirin Dosing
n=17 Participants
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
|
Concentration-Controlled Ribavirin Dosing
n=18 Participants
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
|
|---|---|---|
|
Sustained Virologic Response (i.e., Cure)
|
8 Participants
|
12 Participants
|
Adverse Events
Standard Weight-Based Ribavirin Dosing
Serious events: 4 serious events
Other events: 14 other events
Deaths: 0 deaths
Concentration-Controlled Ribavirin Dosing
Serious events: 7 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard Weight-Based Ribavirin Dosing
n=17 participants at risk
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
|
Concentration-Controlled Ribavirin Dosing
n=18 participants at risk
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
|
|---|---|---|
|
Blood and lymphatic system disorders
Hemoglobin < 8.5 g/dL
|
5.9%
1/17 • Number of events 1 • 48 Weeks
|
11.1%
2/18 • Number of events 2 • 48 Weeks
|
|
Cardiac disorders
Chest pain
|
5.9%
1/17 • Number of events 1 • 48 Weeks
|
5.6%
1/18 • Number of events 1 • 48 Weeks
|
|
Nervous system disorders
Frozen arms
|
5.9%
1/17 • Number of events 1 • 48 Weeks
|
0.00%
0/18 • 48 Weeks
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
5.9%
1/17 • Number of events 1 • 48 Weeks
|
0.00%
0/18 • 48 Weeks
|
|
Gastrointestinal disorders
Tooth pain and vomiting
|
0.00%
0/17 • 48 Weeks
|
5.6%
1/18 • Number of events 1 • 48 Weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma
|
0.00%
0/17 • 48 Weeks
|
5.6%
1/18 • Number of events 1 • 48 Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of breath
|
0.00%
0/17 • 48 Weeks
|
5.6%
1/18 • Number of events 1 • 48 Weeks
|
|
Nervous system disorders
Mood alteration
|
0.00%
0/17 • 48 Weeks
|
5.6%
1/18 • Number of events 1 • 48 Weeks
|
Other adverse events
| Measure |
Standard Weight-Based Ribavirin Dosing
n=17 participants at risk
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
|
Concentration-Controlled Ribavirin Dosing
n=18 participants at risk
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
|
|---|---|---|
|
Blood and lymphatic system disorders
Hemoglobin < 10 g/dL
|
29.4%
5/17 • Number of events 5 • 48 Weeks
|
22.2%
4/18 • Number of events 4 • 48 Weeks
|
|
Blood and lymphatic system disorders
ANC < 1000/mm3
|
52.9%
9/17 • Number of events 9 • 48 Weeks
|
27.8%
5/18 • Number of events 5 • 48 Weeks
|
|
Blood and lymphatic system disorders
Platelets < 75,000/mm3
|
17.6%
3/17 • Number of events 3 • 48 Weeks
|
11.1%
2/18 • Number of events 2 • 48 Weeks
|
|
Blood and lymphatic system disorders
WBC <2000/mm3
|
11.8%
2/17 • Number of events 2 • 48 Weeks
|
16.7%
3/18 • Number of events 3 • 48 Weeks
|
|
Nervous system disorders
Grade 3 Depression
|
5.9%
1/17 • Number of events 1 • 48 Weeks
|
5.6%
1/18 • Number of events 1 • 48 Weeks
|
|
Nervous system disorders
Grade 3 Fatigue
|
11.8%
2/17 • Number of events 2 • 48 Weeks
|
5.6%
1/18 • Number of events 1 • 48 Weeks
|
|
Nervous system disorders
Grade 3 Insomnia
|
11.8%
2/17 • Number of events 2 • 48 Weeks
|
0.00%
0/18 • 48 Weeks
|
|
Nervous system disorders
Grade 3 Mood Alteration
|
11.8%
2/17 • Number of events 2 • 48 Weeks
|
0.00%
0/18 • 48 Weeks
|
|
Skin and subcutaneous tissue disorders
Grade 3 Rash
|
11.8%
2/17 • Number of events 2 • 48 Weeks
|
11.1%
2/18 • Number of events 2 • 48 Weeks
|
|
Respiratory, thoracic and mediastinal disorders
Grade 3 Shortness of Breath
|
23.5%
4/17 • Number of events 4 • 48 Weeks
|
11.1%
2/18 • Number of events 2 • 48 Weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place