Trial Outcomes & Findings for Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects (NCT NCT01563536)
NCT ID: NCT01563536
Last Updated: 2018-07-02
Results Overview
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
Results posted on
2018-07-02
Participant Flow
Participant milestones
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
5
|
4
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Baseline characteristics by cohort
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.5 years
STANDARD_DEVIATION 4.76 • n=5 Participants
|
46.8 years
STANDARD_DEVIATION 11.84 • n=7 Participants
|
49.2 years
STANDARD_DEVIATION 8.94 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)Population: All participants who received at least one dose of study drug (intent-to-treat \[ITT\] population).
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1
|
1.66 ng/mL
Standard Deviation 0.21
|
41.0 ng/mL
Standard Deviation 16.5
|
PRIMARY outcome
Timeframe: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)Population: All participants who received at least one dose of study drug (ITT population).
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Time of maximum plasma concentration (Tmax; measured in hours) was estimated using noncompartmental analyses.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1
|
3.67 hours
Standard Deviation 0.82
|
3.67 hours
Standard Deviation 1.5
|
PRIMARY outcome
Timeframe: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)Population: All participants who received at least one dose of study drug (ITT population).
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC\[24\]; measured in ng multiplied by hour/mL) was estimated using noncompartmental analyses.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1
|
18.0 ng*hr/mL
Standard Deviation 2.46
|
467 ng*hr/mL
Standard Deviation 236
|
PRIMARY outcome
Timeframe: Day 2 (pre-dose) and Day 3 (pre-dose)Population: All participants who received at least one dose of study drug (ITT population).
Blood samples were collected pre-dose on Day 2 (prior to second dose of ABT-267 monotherapy) and pre-dose on Day 3 (prior to first dose of combination therapy). The samples were analyzed for ABT-267 using validated analytical methods. Pre-dose plasma concentrations on Day 2 and Day 3 (Ctrough, measured in ng/mL) are reported.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3
Day 2 Ctrough
|
0 ng/mL
Standard Deviation 0
|
5.2 ng/mL
Standard Deviation 1.78
|
|
Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3
Day 3 Ctrough
|
0.228 ng/mL
Standard Deviation 0.263
|
6.62 ng/mL
Standard Deviation 3.77
|
PRIMARY outcome
Timeframe: All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks).Population: All participants who received at least one dose of study drug (safety population).
An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs), and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening. A serious adverse event was any event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Any AE at least possibly related to DAAs
|
3 participants
|
4 participants
|
|
Number of Participants With Adverse Events (AEs)
Any AE
|
3 participants
|
5 participants
|
|
Number of Participants With Adverse Events (AEs)
Any severe AE
|
0 participants
|
1 participants
|
|
Number of Participants With Adverse Events (AEs)
Any serious AE
|
0 participants
|
2 participants
|
|
Number of Participants With Adverse Events (AEs)
Any AE leading to discontinuation of study drug
|
0 participants
|
1 participants
|
|
Number of Participants With Adverse Events (AEs)
Any AE leading to interruption of study drug
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs)
Any AE leading to RBV dose modification
|
0 participants
|
1 participants
|
|
Number of Participants With Adverse Events (AEs)
Any fatal AE
|
0 participants
|
0 participants
|
|
Number of Participants With Adverse Events (AEs)
Deaths
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Pre-dose on Days 1, 2, and 3Population: All participants who received at least one dose of study drug (ITT population).
The baseline value was the last measurement before the first dose of ABT-267 monotherapy (Day 1). The maximal decrease during monotherapy was the change from baseline to the lowest log10 IU/mL HCV RNA level any time from the first dose of ABT-267 on Day 1 to the last log10 HCV RNA level before the first dose of ABT-267 combination therapy (Study Day 3).
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy
|
-1.6 log10 IU/mL
Standard Error 0.41
|
-3.1 log10 IU/mL
Standard Error 0.41
|
SECONDARY outcome
Timeframe: 12 and 24 weeks after last dose of combination study drugPopulation: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 and 24 weeks after the last dose of combination study drug. The LLOQ for the assay was 25 IU/mL.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy
12 Weeks Post-treatment
|
83.3 percentage of participants
|
83.3 percentage of participants
|
|
Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy
24 Weeks Post-treatment
|
83.3 percentage of participants
|
83.3 percentage of participants
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) after 4 weeks of combination therapy.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Percentage of Participants With Rapid Virologic Response
|
83.3 percentage of participants
|
100 percentage of participants
|
SECONDARY outcome
Timeframe: 12 weeksPopulation: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) at the end of combination therapy (12 weeks).
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Percentage of Participants With End-of-Treatment Response
|
83.3 percentage of participants
|
83.3 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4 to 12Population: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) at Weeks 4 through 12 of combination therapy.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Percentage of Participants With Extended Rapid Virologic Response
|
83.3 percentage of participants
|
83.3 percentage of participants
|
SECONDARY outcome
Timeframe: Predose on Days 1, 2, and 3Population: All participants who received at least one dose of study drug (ITT population).
The relationship between ABT-267 dose, ABT-267 concentration, and response was analyzed as the change in viral load (measured as log10 IU/mL) from baseline (pre-dose on Day 1) to pre-dose on Days 2 and 3. Plasma concentrations of ABT-267 pre-dose on Days 2 and 3 are presented above in 4. Primary Outcome: Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy
Day 2 Mean change in Viral Load from Baseline
|
-1.95 log10 IU/mL
Standard Deviation 0.630
|
-2.85 log10 IU/mL
Standard Deviation 0.421
|
|
Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy
Day 3 Mean change in Viral Load from Baseline
|
-1.96 log10 IU/mL
Standard Deviation 0.405
|
-3.10 log10 IU/mL
Standard Deviation 0.257
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 1 Pre-dose (Baseline) and Day 3 Pre-dosePopulation: All participants who received at least one dose of study drug (ITT population) and had evaluable data were analyzed for baseline resistance-associated amino acid variants; the development of viral resistance was analyzed in all participants who received at least 1 dose of ABT-267 whose samples had sufficient viral titer to allow analysis.
Baseline (pre-dose on Day 1) samples were analyzed for resistance-associated amino acid (AA) variants using population sequencing. Phenotypic resistance to ABT-267 at Baseline was assessed by calculating the fold difference in the the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Day 3 samples were analyzed using population sequencing and were compared with the baseline and appropriate prototypic reference sequences to assess AA changes. Phenotypic resistance at Day 3 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding Baseline sample. The number of participants with variants at resistance-associated AA positions and phenotypic resistance at Baseline and Day 3 are presented.
Outcome measures
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 Participants
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Resistance-Associated Variants and Phenotypic Resistance
Baseline Variants in NS5A (n=5, 6)
|
2 participants
|
0 participants
|
|
Resistance-Associated Variants and Phenotypic Resistance
Baseline Resistance >10-fold (n=5, 6)
|
1 participants
|
0 participants
|
|
Resistance-Associated Variants and Phenotypic Resistance
Day 3 Variants in NS5A (n=5, 2)
|
6 participants
|
2 participants
|
|
Resistance-Associated Variants and Phenotypic Resistance
Day 3 Resistance >10-fold (n=5, 2)
|
1 participants
|
2 participants
|
Adverse Events
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 participants at risk
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 participants at risk
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Infections and infestations
LABYRINTHITIS
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Psychiatric disorders
MANIA
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
Other adverse events
| Measure |
ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 participants at risk
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV
n=6 participants at risk
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Cardiac disorders
TACHYCARDIA
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Gastrointestinal disorders
DIARRHOEA
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
33.3%
2/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Gastrointestinal disorders
DRY MOUTH
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
General disorders
ASTHENIA
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
General disorders
CHEST PAIN
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
General disorders
FATIGUE
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
33.3%
2/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Injury, poisoning and procedural complications
EXCORIATION
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Investigations
BLOOD BILIRUBIN INCREASED
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
33.3%
2/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Investigations
HAEMOGLOBIN DECREASED
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
33.3%
2/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Metabolism and nutrition disorders
VITAMIN D DEFICIENCY
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Nervous system disorders
BURNING SENSATION
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Nervous system disorders
HEADACHE
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
33.3%
2/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Nervous system disorders
RESTLESS LEGS SYNDROME
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Psychiatric disorders
ABNORMAL DREAMS
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Psychiatric disorders
SLEEP DISORDER
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Renal and urinary disorders
DYSURIA
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Respiratory, thoracic and mediastinal disorders
SINUS CONGESTION
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Skin and subcutaneous tissue disorders
DERMATITIS
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
16.7%
1/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.00%
0/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
33.3%
2/6 • All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks).
|
Additional Information
Global Medical Services
AbbVie
Phone: 800-633-9110
Results disclosure agreements
- Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
- Publication restrictions are in place
Restriction type: OTHER