Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as dasabuvir, Exviera, Dasabuvir mini tablet
ABT-333 · 3 trials · 2 indications
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during monotherapy was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level before the first dose of study drug on Day 3. Data are reported as the least squares mean change from nadir ± standard error.
Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during treatment was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level on Day 28. Data are reported as the least squares mean change from nadir ± standard error.
Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) measures the total exposure of a drug in blood plasma. The AUC12 of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation.
Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation.
An AE was any untoward medical occurrence that did not have a causal relationship with treatment. An Adverse Drug Reaction (ADR) was any noxious and undesired reaction related to the experimental drug or experiment. A serious adverse event (SAE) was an AE that resulted in death, was life-threatening, resulted in or prolonged hospitalization, resulted in congenital anomaly, was persistent or caused significant disability/incapacity, spontaneous or elective abortion, or required intervention to prevent a serious outcome. AEs were rated for severity as either: 1. Mild - transient and easily tolerated; 2. Moderate - caused discomfort and interrupted usual activities; 3. Severe - caused considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to direct-acting antiviral agents (DAAs) were assessed as being either probably or possibly related by the investigator.
Participants in studies M10-351 (NCT00851890) and M10-380 (NCT00696904) were analyzed for persistence of resistance-associated variants by comparing post-treatment clonal sequence data with baseline and on-treatment sequence data from M10-351 and M10-380 studies to assess amino acid changes. Phenotypic resistance to ABT-333 was assessed by calculating the fold change in half maximal effective concentration (EC50) of post-treatment samples compared with the EC50 value for the corresponding baseline sample as determined for M10-351 and M10-380 studies. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance at post-treatment time points are presented. Variants are included if the absolute percent of total clones encoding the variant was at least 10% greater than at baseline in a post-treatment sample.
| Arm | Type | Description |
|---|---|---|
| ABT-333 (300 mg) twice daily (BID) + pegIFN/RBV | EXPERIMENTAL | Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-333 (600 mg) twice daily (BID) + pegIFN/RBV | EXPERIMENTAL | Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-333 (1200 mg) once daily (QD) + pegIFN/RBV | EXPERIMENTAL | Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| Placebo + pegIFN/RBV | PLACEBO_COMPARATOR | Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| HCV-infected Participants | OTHER | Hepatitis C virus (HCV)-infected participants who received ABT-333 at any dose level or matching placebo in a prior clinical study involving ABT-333. Participants received no treatment in this follow-up study. |
| 1 | OTHER | Healthy volunteers, receiving 10-1200 mg ABT-333 or placebo, single dose |
| 2 | OTHER | HCV+ treatment-naive subjects receiving 100-300 mg ABT-333 or placebo, multi-dose, QD or BID |
| 3 | OTHER | Healthy volunteers, receiving 100 mg ABT-333, multi-dose, food effect |
| Name | Type | Description |
|---|---|---|
| ABT-333 | DRUG | 50 mg capsules |
| Placebo for ABT-333 | OTHER | Capsule |
| Pegylated interferon | DRUG | Syringe, 180 µg/0.5 mL for subcutaneous injections administered weekly |
| Ribavirin | DRUG | 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day |
| Blood sample collection only | PROCEDURE | Approximately monthly collection of blood samples. |
| Placebo | DRUG | Capsule, see arms for intervention description |
Inclusion Criteria: * Participant has provided written consent. * If female, participant is postmenopausal or surgically sterile. * If male, must be practicing two effective methods of birth control. * Participant is hepatitis C virus (HCV) genotype 1 with HCV ribonucleic acid levels \>50,000 IU/mL...
ABT-333 was studied for the treatment of chronic hepatitis C virus infection, specifically genotype 1 HCV. It was evaluated both as monotherapy and in combination with pegylated interferon and ribavirin in adults 18 years and older. ABT-333 is an investigational small molecule and is not an approved treatment.
ABT-333 was developed by AbbVie Inc., which trades on the New York Stock Exchange under the ticker ABBV. AbbVie sponsored the clinical studies of ABT-333 in hepatitis C virus infection, including the Phase 2 trial NCT00851890 and the resistance follow-up study NCT00726882.
ABT-333 reached Phase 2 clinical development for chronic hepatitis C virus infection. Two Phase 2 trials were completed, and no trials are currently active. ABT-333 is an investigational agent and is not approved by the FDA for any indication.
ABT-333 has been studied in completed trials including NCT00851890, a Phase 2 trial of multiple doses alone and with pegylated interferon and ribavirin in genotype 1 chronic HCV, and NCT00726882, a Phase 2 follow-up assessing resistance in subjects previously treated with ABT-333. A Phase 1 study, NCT00696904, enrolled healthy volunteers and HCV genotype 1 subjects.
Across the reported ABT-333 studies, total enrollment was 168 participants. NCT00851890 enrolled 30 subjects, NCT00726882 enrolled 35 subjects, and NCT00696904 enrolled 133 healthy volunteers and HCV genotype 1 infected subjects. The Phase 2 trials were randomized, double-blind, and placebo-controlled.