A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE)

Silva, Marcelo; Poo, Jorge Luis; Wagner, Frank; Jackson, Mary Lou; Cutler, David L.; Grace, Michael J.; Bordens, Ronald; Cullen, Connie; Harvey, Joann; Laughlin, Mark

doi:10.1016/j.jhep.2006.03.008

Cited by 98 publications

(80 citation statements)

References 18 publications

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“…In comparison, declines ranging from 0.96 log 10 to 2.11 log 10 have been reported with a single dose of PEG-IFN-␣-2b (1 g/kg and 1.5 g/kg, respectively). 23,24 Similarly, declines ranging from 0.86 log 10 to 1.08 log 10 have been reported for HCV patients injected once with 180 g pegylated IFN-␣-2a. 24,25 Therefore, comparison of immune and antiviral activities induced by CPG 10101 and IFN suggests that CPG 10101 may provide similar antiviral effects and modulation of the innate immune response.…”

Section: Discussionmentioning

confidence: 79%

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

et al. 2007

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3) pg/ml increase (P < 0.01); and 2 5 -oligoadenylate synthetase (OAS) had a 163 (؎120.6) pmol/dl increase (P < 0.01). Decreases in HCV RNA also were dose-dependent, with the greatest group geometric mean maximum reduction of 1.69 ؎ 0.618 log 10 (P < 0.05) observed in the 0.75 mg/kg dose group. Decreases >1 log 10 were seen in 22 of 40 patients who received >1 mg CPG 10101, with 3 patients exceeding a 2.5-log 10 reduction.

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Section: Discussionmentioning

confidence: 79%

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

et al. 2007

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“…Despite the existence of consistent data on the therapeutic efficacy of both molecules in coinfected patients, [7][8][9][10][13][14][15] no head-to-head comparisons between the two pegylated interferons have been published so far. In HCV-monoinfected patients [16][17][18][19] and recently in HIV co-infected patients, 20 cross-study comparisons and retrospective analyses of previous data have been published; however, these results are difficult to interpret because trials were not randomized, and the study design, doses of anti-HCV drugs, and baseline characteristics of patients were not consistent among studies. Only preliminary data from two different prospective, comparative studies on HCV-monoinfected patients have been reported recently.…”

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confidence: 99%

Randomized trial comparing pegylated interferon α‐2b versus pegylated interferon α‐2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients†

et al. 2009

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. At baseline, both groups were well balanced: 73% male; 63% HCV genotype 1 through 4; 29% had fibrosis index of 3 or greater. The overall SVR was 44% (42% PEG 2b versus 46% PEG 2a, P ‫؍‬ 0.65). Among genotypes 1 through 4, SVRs were 28% versus 32% (P ‫؍‬ 0.67) and 62% versus 71% (P ‫؍‬ 0.6) in genotypes 2 through 3 for PEG 2b and PEG 2a, respectively. Early virological response (EVR; >2 log reduction from baseline or negative HCV-RNA at week 12) was 70% in the PEG 2b group and 80% in the PEG 2a group (P ‫؍‬ 0.13), reaching a positive predictive value of SVR of 64% and a negative predictive value of 100% in both arms. Side effects were present in 96% of patients but led to treatment discontinuation in 10% of patients (8% on PEG 2b and 13% on PEG 2a, P ‫؍‬ 0.47). Conclusion: In patients with HIV, HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety. (HEPATOLOGY 2009;49:22-310.)

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“…On the other hand, the diabetic rats lost significant weight during phase B (with loss of muscle and subcutaneous fat) associated with disease progression. Body weight and body mass index (BMI) are also known to play an important role in SC administration in humans (50)(51)(52). Obese subjects have lower fasting and post-prandial SC abdominal adipose tissue blood flow and basal adipose tissue blood flow is negatively correlated with BMI (53).…”

Section: Discussionmentioning

confidence: 99%

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

Chadha

Morris

2015

AAPS J

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Abstract. The objective of this research was to assess the effects of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) on the pharmacokinetics of human IgG (hIgG), an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Furthermore, the specific role of T2DM in the altered disposition of hIgG was evaluated by treating diabetic rats with pioglitazone, while the role of chronic kidney disease (CKD) was assessed using 5/6 nephrectomized Sprague Dawley rats. ZDF male (lean non-diabetic control and obese diabetic) and pioglitazone-treated ZDF rats were studied at ages 12-13 weeks (only DM was present), and at ages 29-30 weeks (progression to DN). All animals were dosed with 1 mg/kg of hIgG intravenously (IV) or subcutaneously (SC). ZDF rats had significantly higher blood glucose concentrations and urinary albumin excretion compared to control rats. Significant increases in total clearance (2.5-fold) and renal clearance (100-fold) of hIgG were observed; however the major increase in total clearance was due to increased non-renal clearance. Greater changes in urinary albumin excretion and total and renal clearances of IgG (3.5-fold and 300-fold, respectively) were observed with progression to DN. SC bioavailability of hIgG in all animal groups was similar (>84%). With pioglitazone-treatment, diabetic animals remained euglycemic and treatment was able to reverse the clearance changes, although incompletely. In the CKD group, no difference in hIgG clearance was observed when compared with controls. In conclusion, the increased clearance of hIgG in ZDF diabetic animals, reversal by pioglitazone treatment and lack of effect of CKD, demonstrate the influence of T2DM on hIgG pharmacokinetics.

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A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE)

Cited by 98 publications

References 18 publications

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

Randomized trial comparing pegylated interferon α‐2b versus pegylated interferon α‐2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients†

Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat

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