FDA Approved Changes to Incivek (telaprevir) Product Labeling to Include OPTIMIZE Trial Results
FDA approved changes to the
Incivek (telaprevir) product labeling to include results from trial C211
(OPTIMIZE) to support a twice daily dosing regimen. In addition new
contraindications were added for anticonvulsant medications (carbamazepine,
phenobarbital and phenytoin) and other revisions to the section 7 Drug
Interactions. Below is a summary of the changes
Additional Data from Clinical Trials
analysis of an additional study (Trial C211), the safety profile of combination
treatment with INCIVEK 1125 mg twice daily was similar to the safety profile
for patients receiving combination treatment with INCIVEK 750 mg every 8 hours
(q8h) [see Clinical Studies (14.2)]. No new safety findings were identified.
total exposure (AUC24h,ss) was similar regardless of whether the total daily
dose of 2250 mg was administered as 750 mg every 8 hours or 1125 mg twice
the data from interaction trials with carbamazepine and phenytoin were included.
C211 Phase 3 clinical trial, there were no differences in the types of emerging
variants between subjects receiving telaprevir 1125 mg twice daily and subjects
receiving telaprevir 750 mg every 8 hours. Similar proportions of subjects in
both treatment groups had telaprevir-resistant variants at the time of failure.
In Trial C211, all subjects were
prospectively tested for IL28B variants; there were no clinically relevant
differences in SVR12 responses between q8h and twice-daily dosing within the
SVR, n/N (%)
T12 Twice Daily/PR
was a randomized, open-label, Phase 3 trial conducted in treatment‑naïve
subjects. Enrolled subjects received 12 weeks of either INCIVEK 750 mg
every 8 hours [T12 (q8h)/PR] or INCIVEK 1125 mg twice daily [T12
(twice daily)/PR] in combination with peginterferon alfa‑2a and ribavirin. The
trial was designed to compare twice-daily dosing [T12 (twice daily)/PR] versus
q8h dosing [T12 (q8h)/PR] of INCIVEK. At week 12, INCIVEK dosing ended and
subjects continued on peginterferon alfa‑2a and ribavirin treatment. The total
treatment duration was determined based on the subjects’ individual
on-treatment viral response. If a subject achieved undetectable HCV RNA
< 25 IU/mL (target not detected) at week 4, the total
treatment duration was 24 weeks. Otherwise, the total treatment duration
was 48 weeks.
740 enrolled subjects had a median age of 51 years (range:
18 to 70); 60% of the subjects were male; 21% had a body
mass index ≥ 30 kg/m2; 5% were Black; 2% were
Asian; 85% had baseline HCV RNA levels ≥ 800,000 IU/ml;
15% had bridging fibrosis; 14% had cirrhosis; 57% had HCV
genotype 1a; and 43% had HCV genotype 1b.
Table 11 shows the response rates
for the T12 (twice daily)/PR group and the T12 (q8h)/PR groups by treatment
outcomes. The overall SVR rates were similar at 74% [T12 (twice daily)/PR;
274/369] and 73% [T12 (q8h)/PR; 270/371], respectively.
Response Rates: Trial C211
T12 (twice daily)/PR
N = 369
N = 371
Undetectable HCV RNA (target not detected) at week 4a
SVR in subjects with undetectable HCV RNA (target not detected) at
SVR in subjects who did not have undetectable HCV RNA at week 4
Outcome for Subjects without
On‑treatment virologic failureb
T12 (twice daily)/PR: INCIVEK 1125 mg twice daily for 12 weeks with
peginterferon alfa‑2a and ribavirin for 24 or 48 weeks; T12
(q8h)/PR: INCIVEK 750 mg every 8 hours for 12 weeks with
peginterferon alfa‑2a and ribavirin for 24 or 48 weeks
a Subjects with planned total treatment duration of
b On‑treatment‑virologic failure includes subjects who
met a protocol‑defined virologic stopping rule and/or who had detectable HCV
RNA at the time of their last dose of study drug and had viral breakthrough.
c Relapse was defined as having less than 25 IU/mL at
the planned end of treatment followed by HCV RNA ≥ 25 IU/ml at the
last observation within the SVR follow-up visit window.
d Other includes
subjects with detectable HCV RNA at the planned end of treatment but who did
not have viral breakthrough, and subjects with a missing SVR assessment
during planned follow-up.
SVR rates were similar for
the T12 (twice daily)/PR and T12 (q8h)/PR groups across subgroups determined by
sex, age, race, ethnicity, body mass index, HCV genotype subtype, IL28B
genotype, baseline HCV RNA (less than 800,000, greater than or equal to 800,000 IU
per mL), and extent of liver fibrosis. However, there were small numbers of
subjects enrolled in some key subgroups.
Fifty-four and 49
subjects in T12 (twice daily)/PR and T12 (q8h)/PR groups, respectively, had
cirrhosis at baseline. The SVR rate in these subjects was 54% (29/54) in the
T12 (twice daily)/PR group and 49% (24/49) in the T12 (q8h)/PR group. In the
T12 (twice daily)/PR group, 52% (28/54) of subjects with cirrhosis achieved
undetectable HCV RNA (target not detected) at week 4; their SVR rate was 68%
(19/2. In the T12 (q8h)/PR group, 59% (29/49) achieved undetectable HCV
RNA (target not detected) at week 4; their SVR was 59% (17/29). The SVR rate
for subjects assigned 48 weeks of treatment was 38% (10/26) in the T12 (twice
daily)/PR group and 35% (7/20) in the T12 (q8h)/PR.
subjects were Black/African Americans. The overall SVR among Black/African
American subjects was 50% (10/20) in the T12 (twice daily)/PR group and 60%
(9/15) in the T12 (q8h)/PR group. Among these subjects, 46% (16/35) were
assigned to 24 weeks of treatment and of those 88% (14/16) achieved SVR.