ライフサイエンスコーパス: boceprevir

1 gylated IFN-alpha, ribavirin, and telaprevir/boceprevir.

2 could affect binding of telaprevir more than boceprevir.

3 s were similar with 24 weeks and 44 weeks of boceprevir.

4 ginterferon and ribavirin with telaprevir or boceprevir.

5 ts of the phase III trials for telaprevir or boceprevir.

6 response to prior therapy with telaprevir or boceprevir.

7 ketoamide fragment of the protease inhibitor boceprevir.

8 kin rash and anal discomfort by switching to boceprevir.

9 PI/r resulted in reduced exposures of PI and boceprevir.

10 ded for combined HIV/HCV treatment including boceprevir.

11 ho failed earlier therapy with telaprevir or boceprevir.

12 The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and ef

13 han the first generation clinical candidate, boceprevir (1, Sch 503034), is discussed.

14 ibavirin without (46%) or with telaprevir or boceprevir (12%).

15 pegylated interferon, ribavirin, and either boceprevir (2 trials) or telaprevir (4 trials) was assoc

16 Among those given boceprevir, 53.9% of relapsers, 38.3% of partial respond

17 l subjects were randomly assigned to receive boceprevir 800 mg every 8 hours for 9 days plus a single

18 wed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PR

19 After washout, they received boceprevir (800 mg three times a day) for 11 days plus s

20 After washout, subjects received boceprevir (800 mg three times a day) for 7 days plus si

21 In part 2B, 10 subjects received single-dose boceprevir (800 mg) and 24 hours later received boceprev

22 cyclosporine (100 mg) on day 1, single-dose boceprevir (800 mg) on day 3, and concomitant cyclospori

23 eprevir (800 mg) and 24 hours later received boceprevir (800 mg) plus tacrolimus (0.5 mg).

24 Subjects received boceprevir (800 mg, 3 times daily) for 6 days and then r

25 and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon

26 Boceprevir, a potent oral HCV-protease inhibitor, has be

27 Boceprevir, a protease inhibitor that binds to the HCV n

28 istinct from the FDA-approved telaprevir and boceprevir alpha-ketoamide inhibitors, are required.

29 interactions have been demonstrated between boceprevir, an HCV protease inhibitor, and frequently pr

30 We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhib

31 n about pharmacokinetic interactions between boceprevir and antiretroviral drugs.

32 low-level resistance to telaprevir (TVR) and boceprevir and confers high-level resistance (>70-fold)

33 To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment o

34 treatment With HCV Serine Protease Inhibitor Boceprevir and Pegintron/Rebetol 2 (RESPOND-2) study (tr

35 treatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) re

36 rol group (n = 66) received a combination of boceprevir and PR, dosed in accordance with boceprevir's

37 e absence of a drug-drug interaction between boceprevir and raltegravir, an HIV integrase inhibitor.

38 ess the pharmacokinetic interactions between boceprevir and ritonavir-boosted protease inhibitors (PI

39 Boceprevir and telaprevir are inhibitors and substrates

40 We analyzed data from boceprevir and telaprevir clinical trials to obtain a co

41 Retrospective analyses of the boceprevir and telaprevir phase 3 trial data demonstrate

42 dition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (pegin

43 Analyses of Phase 2 boceprevir and telaprevir trials indicated subjects with

44 itaprevir/ritonavir +/- dasabuvir as well as boceprevir and telaprevir triple therapy was assessed us

45 nt emergence of two new protease inhibitors, boceprevir and telaprevir, to enhance the modern treatme

46 These DAAs, boceprevir and telaprevir, when given with pegylated int

47 US Food and Drug Administration approval of boceprevir and telaprevir--two protease inhibitors--the

48 t promising protease inhibitors, telaprevir, boceprevir, and ITMN-191, has emerged in clinical trials

49 During boceprevir- and telaprevir-based treatment, subjects wit

50 Boceprevir- and telaprevir-based treatments for chronic

51 Telaprevir and boceprevir are structurally similar, and share cross-res

52 followed by guideline-based treatment (using boceprevir as the direct-acting antiviral agent) of thos

53 r by the NS3 protease inhibitors telaprevir, boceprevir, asunaprevir, simeprevir, vaniprevir, faldapr

54 The GM of boceprevir AUC(0-8h), C(max), and C(8h) were 5.45 (95% C

55 ignificantly affect boceprevir exposure, but boceprevir AUC(tau) was reduced by 45% and 32% when coad

56 Boceprevir-based and telaprevir-based triple therapy wit

57 stopping rules for patients destined to fail boceprevir-based combination therapy in order to minimiz

58 Boceprevir-based groups had higher rates of anaemia (227

59 static hepatitis treated with telaprevir- or boceprevir-based triple therapy at 6 centers (CRUSH-C co

60 hibitors VX-950 (telaprevir) and SCH 503034 (boceprevir) benefited from covalent adduct formation.

61 Boceprevir (BOC) added to peginterferon alfa-2b (PegIFN)

62 Boceprevir (BOC) and telaprevir (TPV), when added to peg

63 bavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and s

64 TT) with peginterferon alpha, ribavirin, and boceprevir (BOC) or telaprevir (TVR) is more effective t

65 In clinical trials with telaprevir (TLV) and boceprevir (BOC) renal impairment was not reported as a

66 SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untre

67 esponse-guided shortening of the duration of boceprevir (BOC)-based triple therapy in human immunodef

68 esponse-guided shortening of the duration of boceprevir (BOC)-based triple therapy in human immunodef

69 inant was highly resistant to telaprevir and boceprevir, but most sensitive to other protease inhibit

70 In Phase 3 trials P05216 (boceprevir), C216 (telaprevir), and 108 (telaprevir), de

71 Coadministration with boceprevir decreased RTV AUC during a dosing interval ta

72 Boceprevir decreased the exposure of all PI/r, with area

73 ATV/r did not significantly affect boceprevir exposure, but boceprevir AUC(tau) was reduced

74 ents receiving peginterferon, ribavirin, and boceprevir for HCV infection.

75 Study arms that evaluated telaprevir or boceprevir for unlicensed durations or without both pegy

76 pproval of two new DAA drugs--telaprevir and boceprevir--for use in pegylated interferon-based and ri

77 V protease inhibitors such as telaprevir and boceprevir, given in combination with pegylated IFN and

78 40 (63%) of 64 patients in the boceprevir group had an SVR at follow-up week 24, compar

79 p) or 800 mg boceprevir three times per day (boceprevir group) for 44 weeks.

80 response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in t

81 Patients in all four boceprevir groups had higher rates of SVR than did the c

82 Anemia was significantly more common in the boceprevir groups than in the control group, and erythro

83 should be anticipated when administered with boceprevir, guided by close monitoring of cyclosporine b

84 al for drug interactions with telaprevir and boceprevir had not been answered.

85 previr response-guided therapy (BOC-RGT); 2) boceprevir IL28B genotype-guided strategy (BOC-IL28B); 3

86 Boceprevir in combination with peginterferon-ribavirin c

87 elaprevir had greater relative efficacy than boceprevir in patients who had previously relapsed.

88 , and we further confirmed its resistance to boceprevir in protease enzyme and replicon assay.

89 Concomitant boceprevir increased the area under the concentration-ti

90 Concomitant boceprevir increased the AUC(inf) and C(max) of tacrolim

91 The hepatitis C virus protease inhibitor boceprevir is a strong inhibitor of cytochrome P450 3A4

92 ginterferon and ribavirin with telaprevir or boceprevir is the standard treatment of hepatitis C viru

93 suspected cause whereby CYP3A4 inhibition by boceprevir led to increased exposures of doxazosin, tams

94 The key structural feature in Boceprevir, Merck's new drug treatment for hepatitis C,

95 s) were given either telaprevir (n = 299) or boceprevir (n = 212) for 48 weeks.

96 elaprevir had greater relative efficacy than boceprevir (odds ratio [OR], 2.61 [95% confidence interv

97 0 mg) on day 3, and concomitant cyclosporine/boceprevir on day 4.

98 (RTV) 100 mg on days 10-31, plus concomitant boceprevir on days 25-31.

99 e genotype 1a protease, co-crystallized with boceprevir or a telaprevir-like ligand, and then identif

100 nd ribavirin), or 3-drug therapy with either boceprevir or sofosbuvir.

101 The combination of boceprevir or telaprevir with peginterferon-alfa and rib

102 ectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-pot

103 nfected patients who are currently receiving boceprevir or telaprevir-based therapy against HCV show

104 OR, 3.24 [95% CI, 2.56-4.10]); telaprevir vs boceprevir (OR, 1.06 [95% CI, 0.75-1.47]).

105 891) (OR, 8.32 [5.69-12.36]); telaprevir vs boceprevir (OR, 1.27 [95% CI, .71-2.30]).

106 peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy

107 nt of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to ane

108 coadministration had a meaningful effect on boceprevir pharmacokinetics.

109 revious virologic failure with telaprevir or boceprevir plus peginterferon alfa-ribavirin).

110 Three patients who received boceprevir plus peginterferon-ribavirin and four control

111 ron-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, an

112 ron-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks, an

113 an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks.

114 an additional 12 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks.

115 s efficacy and safety of triple therapy with boceprevir plus pegylated interferon alfa-2b (peginterfe

116 Administration of boceprevir plus tacrolimus requires significant dose red

117 28B genotype-guided strategy (BOC-IL28B); 3) boceprevir rapid virologic response (RVR)-guided strateg

118 In boceprevir recipients, the combination of 2 stopping rul

119 ose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2

120 Boceprevir represents a new treatment option for hepatit

121 the following five competing strategies: 1) boceprevir response-guided therapy (BOC-RGT); 2) bocepre

122 Usual care (boceprevir-ribavirin-pegylated interferon [PEG]) was com

123 boceprevir and PR, dosed in accordance with boceprevir's US product circular.

124 improve upon our current clinical candidate, Boceprevir (SCH 503034), extensive SAR studies were perf

125 Recently, we disclosed the discovery of Boceprevir, SCH 503034 (1), a novel, potent, selective,

126 dies with our first generation HCV inhibitor Boceprevir, SCH 503034 (1), presented at the 56th Annual

127 gylated interferon and ribavirin plus either boceprevir, telaprevir, or simeprevir.

128 ts were more common in patients who received boceprevir than in control patients: 26 (41%) versus nin

129 ors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the NS5B polymerase inhibitor AG-021541; and

130 3); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107)

131 (400-1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB4

132 lus either placebo (control group) or 800 mg boceprevir three times per day (boceprevir group) for 44

133 The addition of boceprevir to peginterferon-ribavirin resulted in signif

134 The addition of boceprevir to standard therapy with peginterferon-ribavi

135 ddition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and

136 thropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls.

137 Compared with dual therapy, boceprevir triple therapy increased risk for hematologic

138 ks of peginterferon alpha-2b, ribavirin, and boceprevir (triple therapy).

139 3/4A protease, telaprevir (Incivik((R))) and boceprevir (Victrelis((R))).

140 protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis) are the first direct-acting antiv

141 avir AUC(0-12h) and C(max) for raltegravir + boceprevir vs raltegravir alone were 1.04 (90% CI, .88-1

142 sma concentration (C(max)) for raltegravir + boceprevir vs raltegravir alone were 4.27 (95% confidenc

143 Treatment-naive patients: boceprevir vs standard of care (n = 1417) (OR, 3.06 [95%

144 Total treatment-experienced population: boceprevir vs standard of care (n = 604) (OR, 6.53 [95%

145 hase II clinical study of protease inhibitor boceprevir, we calculated the selection pressure for all

146 At key RGT timepoints (week 8 for boceprevir, week 4 for telaprevir), subjects with detect

147 able for an additional 8 (telaprevir) to 20 (boceprevir) weeks (extended RVR).

148 Telaprevir and boceprevir were approved in 2011 for use against genotyp

149 , novel HCV NS3/4A PIs (PIs), telaprevir and boceprevir, were approved for use in combination with Pe

150 atitis C protease inhibitors, telaprevir and boceprevir, were shown to have antiviral activity in hep

151 may reduce the effectiveness of PI/r and/or boceprevir when coadministered.

152 These agents, telaprevir and boceprevir, when used in combination with pegylated inte

153 pharmacokinetic interaction study evaluated boceprevir with cyclosporine (part 1) and tacrolimus (pa

154 Coadministration of boceprevir with cyclosporine/tacrolimus was well tolerat

155 mparison with peginterferon/ribavirin alone, boceprevir with peginterferon/ribavirin significantly im

156 Concomitant administration of boceprevir with PI/r resulted in reduced exposures of PI

157 Concomitant administration of boceprevir with these drugs should be avoided.