SUMMARY
REBETOL is Schering Corporation's brand name for ribavirin, a nucleoside analog with antiviral activity.
REBETOL (ribavirin, USP) Capsules is indicated in combination with INTRON A (interferon alfa-2b, recombinant) Injection for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon or who have relapsed following alpha interferon therapy.
Previously Untreated Patients Adults with compensated chronic hepatitis C and detectable HCV RNA (assessed by a central laboratory using a research-based RT-PCR assay) who were previously untreated with alpha interferon therapy were enrolled into two multicenter, double-blind trials (US and International) and randomized to receive REBETOL Capsules 1200 mg/day (1000 mg/day for patients weighing </=75 kg) plus INTRON A Injection 3 MIU TIW or INTRON A Injection plus placebo for 24 or 48 weeks followed by 24 weeks of off-therapy follow-up. The International study did not contain a 24-week INTRON A plus placebo treatment arm. The US study enrolled 912 patients who, at baseline, were 67% male, 89% caucasian with a mean Knodell HAI score (I+II+III) of 7.5, and 72% genotype 1. The International study, conducted in Europe, Israel, Canada, and Australia, enrolled 799 patients (65% male, 95% caucasian, mean Knodell score 6.8, and 58% genotype 1).
Study results are summarized in TABLE 3.
TABLE 3. Virologic and Histologic Responses: Previously Untreated Patients *
|
|
US Study
|
International Study
|
24 weeks
of treatment
|
48 weeks
of treatment
|
24 weeks
of treatment
|
48 weeks
of treatment
|
INTRON A
plus
REBETOL
(N=228) |
INTRON A
plus
Placebo
(N=231) |
INTRON A
plus
REBETOL
(N=228) |
INTRON A
plus
Placebo
(N=225) |
INTRON A
plus
REBETOL
(N=265) |
INTRON A
plus
REBETOL
(N=268) |
INTRON A
plus
Placebo
(N=266) |
Virologic
Response |
|
-Responder1 |
65 (29) |
13 (6)
|
85 (37) |
27 (12) |
86 (32) |
113 (42) |
46 (17) |
|
-Nonresponder
|
147 (64) |
194 (84) |
110 (48) |
168 (75) |
158 (60) |
120 (45) |
196 (74) |
|
-Missing data
|
16 (7)
|
24 (10) |
33 (14) |
30 (13) |
21 (8)
|
35 (13) |
24 (9)
|
Histologic
Response |
|
-Improvement2 |
102 (45) |
77 (33) |
96 (42) |
65 (29) |
103 (39) |
102 (38) |
69 (26) |
|
-No improvement
|
77 (34) |
99 (43) |
61 (27) |
93 (41) |
85 (32) |
58 (22) |
111 (41) |
|
-Missing data
|
49 (21) |
55 (24) |
71 (31) |
67 (30) |
77 (29) |
108 (40) |
86 (32) |
|
*Number (%) of patients
|
| 1 Defined as HCV RNA below limit of detection using a research-based RT-PCR assay at end of treatment and during follow-up period.
|
| 2 Defined as posttreatment (end of follow-up) minus pretreatment liver biopsy Knodell HAI score (I+II+III) improvement of >/=2 points. |
|
Of patients who had not achieved HCV RNA below the limit of detection of the research-based assay by week 24 of REBETOL/INTRON A treatment, less than 5% responded to an additional 24 weeks of combination treatment.
Among patients with HCV genotype 1 treated with REBETOL/INTRON A therapy who achieved HCV RNA below the detection limit of the research-based assay by 24 weeks, those randomized to 48 weeks of treatment had higher virologic responses compared to those in the 24-week treatment group. There was no observed increase in response rates for patients with HCV nongenotype 1 randomized to REBETOL/INTRON A therapy for 48 weeks compared to 24 weeks.
Relapse Patients Patients with compensated chronic hepatitis C and detectable HCV RNA (assessed by a central laboratory using a research-based RT-PCR assay) who had relapsed following one or two courses of interferon therapy (defined as abnormal serum ALT levels) were enrolled into two multicenter, double-blind trials (US and International) and randomized to receive REBETOL 1200 mg/day (1000 mg/day for patients weighing </=75 kg) plus INTRON A 3 MIU TIW or INTRON A plus placebo for 24 weeks followed by 24 weeks of off-therapy follow-up. The US study enrolled 153 patients who, at baseline, were 67% male, 92% caucasian with a mean Knodell HAI score (I+II+III) of 6.8, and 58% genotype 1. The International study, conducted in Europe, Israel, Canada, and Australia, enrolled 192 patients (64% male, 95% caucasian, mean Knodell score 6.6, and 56% genotype 1).
Study results are summarized in TABLE 4.
TABLE 4. Virologic and Histologic Responses: Relapse Patients *
|
|
US Study
|
International Study
|
INTRON A
plus
REBETOL
(N=77) |
INTRON A
plus
Placebo
(N=76) |
INTRON A
plus
REBETOL
(N=96) |
INTRON A
plus
Placebo
(N=96) |
Virologic
Response |
|
-Responder1 |
33 (43) |
3 (4) |
46 (48) |
5 (5) |
|
-Nonresponder
|
36 (47) |
66 (87) |
45 (47) |
91 (95) |
|
-Missing data
|
8 (10) |
7 (9) |
5 (5) |
0 (0) |
Histologic
Response |
|
-Improvement2 |
38 (49) |
27 (36) |
49 (51) |
30 (31) |
|
-No improvement
|
23 (30) |
37 (49) |
29 (30) |
44 (46) |
|
-Missing data
|
16 (21) |
12 (16) |
18 (19) |
22 (23) |
|
*Number (%) of patients
|
| 1 Defined as HCV RNA below limit of detection using a research-based RT-PCR assay at end of treatment and during follow-up period.
|
| 2 Defined as posttreatment (end of follow-up) minus pretreatment liver biopsy Knodell HAI score (I+II+III) improvement of >/=2 points. |
|
Virologic and histologic responses were similar among male and female patients in both the previously untreated and relapse studies.
|
