AI
Thursday, October 01, 2009 5:00:16 PM
AASLD ABT-333 abstract:
Treatment-naïve, HCV genotype 1-infected subjects show significantly greater HCV RNA decreases when treated with 28 days of ABT-333 plus peginterferon and ribavirin compared to peginterferon and ribavirin alone
M. Rodriguez-Torres1; E. Lawitz2; D. Cohen3; L. M. Larsen3; R. Menon3; C. Collins3; T. Marsh3; S. Gibbs3; B. Bernstein3
1. Fundación de Investigación de Diego, San Juan, PR, USA.
2. Alamo Medical Research, San Antonio, TX, USA.
3. Abbott Laboratories, Abbott Park, IL, USA.
Objective: ABT-333 is a potent nonnucleoside HCV polymerase inhibitor with a favorable safety profile in healthy subjects. This study assesses the safety, antiviral activity, and pharmacokinetics (PK) of ABT-333 with peginterferon alfa-2a (pegIFN) and ribavirin (RBV) in HCV-infected subjects.
Methods: 30 HCV genotype 1-infected, treatment-naïve subjects were randomized to ABT-333 300 mg BID (N=8), 600 mg BID (N=8), 1200 mg QD (N=8), or placebo (n=6) for 28 days (2 days monotherapy plus 26 days with pegIFN 180 mcg/wk + RBV 1000-1200 mg/d, weight-based). Safety was monitored by adverse events (AEs) and lab results. ABT-333 PK profile was assessed on Day 1; samples were also collected Days 2, 4, 5, 10, 17, 24 and 28.
Results: Subjects were primarily male (70%) and white (90%); 43% were of Latino ethnicity. At baseline, the mean (SD) age was 46.5 (9.8) yrs and the mean weight was 78.6 (13.2) kg. Treatment with ABT-333+pegIFN/RBV resulted in statistically significantly greater decreases in HCV RNA versus placebo+pegIFN/RBV (Figure). The least square mean maximum HCV RNA change from baseline was -3.7, -4.0, and -3.5 log10 IU/mL for 300 mg BID, 600 mg BID, and 1200 mg QD ABT-333+pegIFN/RBV, respectively, compared to -1.4 log10 IU/mL for placebo+pegIFN/RBV. Mean ABT-333 Cmax and AUC increased with increasing doses and were comparable to healthy subjects. Based on mean trough values, addition of pegIFN/RBV did not alter ABT-333 PK. AEs were generally mild and attributed to pegIFN or RBV. Of ABT-333-associated AEs, nausea, headache, flatulence, and dermatitis were most common (N=2-3 for each AE). There were no serious AEs or discontinuations due to AEs. Lab abnormalities were similar in subjects receiving ABT-333 and placebo.
Conclusion: ABT-333 was well tolerated for 28 days when dosed with pegIFN/RBV and resulted in significant decreases in HCV RNA versus pegIFN/RBV alone.
Treatment-naïve, HCV genotype 1-infected subjects show significantly greater HCV RNA decreases when treated with 28 days of ABT-333 plus peginterferon and ribavirin compared to peginterferon and ribavirin alone
M. Rodriguez-Torres1; E. Lawitz2; D. Cohen3; L. M. Larsen3; R. Menon3; C. Collins3; T. Marsh3; S. Gibbs3; B. Bernstein3
1. Fundación de Investigación de Diego, San Juan, PR, USA.
2. Alamo Medical Research, San Antonio, TX, USA.
3. Abbott Laboratories, Abbott Park, IL, USA.
Objective: ABT-333 is a potent nonnucleoside HCV polymerase inhibitor with a favorable safety profile in healthy subjects. This study assesses the safety, antiviral activity, and pharmacokinetics (PK) of ABT-333 with peginterferon alfa-2a (pegIFN) and ribavirin (RBV) in HCV-infected subjects.
Methods: 30 HCV genotype 1-infected, treatment-naïve subjects were randomized to ABT-333 300 mg BID (N=8), 600 mg BID (N=8), 1200 mg QD (N=8), or placebo (n=6) for 28 days (2 days monotherapy plus 26 days with pegIFN 180 mcg/wk + RBV 1000-1200 mg/d, weight-based). Safety was monitored by adverse events (AEs) and lab results. ABT-333 PK profile was assessed on Day 1; samples were also collected Days 2, 4, 5, 10, 17, 24 and 28.
Results: Subjects were primarily male (70%) and white (90%); 43% were of Latino ethnicity. At baseline, the mean (SD) age was 46.5 (9.8) yrs and the mean weight was 78.6 (13.2) kg. Treatment with ABT-333+pegIFN/RBV resulted in statistically significantly greater decreases in HCV RNA versus placebo+pegIFN/RBV (Figure). The least square mean maximum HCV RNA change from baseline was -3.7, -4.0, and -3.5 log10 IU/mL for 300 mg BID, 600 mg BID, and 1200 mg QD ABT-333+pegIFN/RBV, respectively, compared to -1.4 log10 IU/mL for placebo+pegIFN/RBV. Mean ABT-333 Cmax and AUC increased with increasing doses and were comparable to healthy subjects. Based on mean trough values, addition of pegIFN/RBV did not alter ABT-333 PK. AEs were generally mild and attributed to pegIFN or RBV. Of ABT-333-associated AEs, nausea, headache, flatulence, and dermatitis were most common (N=2-3 for each AE). There were no serious AEs or discontinuations due to AEs. Lab abnormalities were similar in subjects receiving ABT-333 and placebo.
Conclusion: ABT-333 was well tolerated for 28 days when dosed with pegIFN/RBV and resulted in significant decreases in HCV RNA versus pegIFN/RBV alone.
Join the InvestorsHub Community
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
