Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
ABT-333 · 4 trials · 3 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.
ABT-333 concentrations in blood
| 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. |
| Arm 1: ABT-333 | EXPERIMENTAL | A single centre, open-label, 4-treatment, 3-period, 4-sequence incomplete randomised, single dose crossover study in healthy subjects. |
| 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 is an investigational small molecule being developed for chronic Hepatitis C Virus (HCV) infection. It has been studied in clinical trials for HCV infection, including genotype 1 chronic hepatitis C, and for relative bioavailability assessment in healthy subjects. It is not approved and remains in clinical development.
ABT-333 is a small molecule antiviral agent studied for the treatment of Hepatitis C Virus (HCV) infection. It has been evaluated in combination with pegylated interferon and ribavirin in clinical trials. The specific molecular target is not disclosed in the available data.
ABT-333 is being developed by AbbVie Inc., a biopharmaceutical company listed on the New York Stock Exchange under the ticker ABBV. The company has sponsored clinical trials evaluating the drug for chronic Hepatitis C Virus infection and related conditions.
ABT-333 has completed Phase 1 and Phase 2 clinical trials. The most advanced trials are Phase 2 studies, which have been completed. The drug is investigational and has not received FDA approval. No active trials are currently listed for ABT-333.
ABT-333 has been studied in several completed clinical trials, including NCT00696904, a Phase 1 study in healthy volunteers and HCV-infected subjects; NCT00726882, a Phase 2 follow-up resistance assessment; NCT00851890, a Phase 2 study of ABT-333 alone and with pegylated interferon and ribavirin; and NCT02052349, a Phase 1 bioavailability study.
ABT-333 is also known as dasabuvir, an antiviral drug used in combination therapies for chronic Hepatitis C Virus infection. It was developed by AbbVie and has been evaluated in clinical trials for HCV genotype 1 infection. The drug is not FDA approved as a standalone therapy.