s and 40 the most severe symptoms. The CGI-I Scale allows the investigator to rate the patients overall change in RLS symptoms since baseline, whether or not in the opinion of the investigator the change is related to study drug treatment. The change from baseline in the IRLS Rating Scale at Week 12 and the proportion of responders on the CGI-I Scale defined as a rating of "much improved" or "very much improved" at Week 12 were co-primary outcomes in these studies.
In these 2 studies, the mean age of patients studied was 50 years (range: 18 to 81 years); 59% of the patients were female. The racial distribution for these studies was as follows: Caucasian, 95%; black, 2%; and other, 3%.
Statistically significant differences (P<0.05) between the treatment groups receiving 600 and 1,200 mg of HORIZANT and the group receiving placebo were observed at Week 12 for both the mean change from baseline in the IRLS Scale total score and the proportion of responders ("much improved" or "very much improved") on the CGI-I Scale as described in Table 6.
Table 6. Mean Change in IRLS Scale Total Score and Proportion of Responders on CGI-I Scale at Week 12 a CGI-I Responders = "much improved" and "very much improved."
Study 1 Study 2
Week 12 HORIZANT
1,200 mg
(N = 112) Placebo
(N = 108) HORIZANT
600 mg
(N = 114) HORIZANT
1,200 mg
(N = 111) Placebo
(N = 96)
Mean change in IRLS Score -13.2 -8.8 -13.8 -13.0 -9.8
Proportion of Respondersa on CGI-I 76% 39% 73% 77% 45%
Figure 1 presents the improvement in mean IRLS Rating Scale total score in patients treated with placebo or 600 or 1,200 mg of HORIZANT over the 12 weeks of treatment in study 2.
Figure 1. Study 2, Mean (±SD) IRLS Rating Scale Total Score Over 12 Weeks (Observed Case Data, Modified Intent-To-Treat Population)
14.2 Postherpetic Neuralgia (PHN) 12 Week StudyThe efficacy of HORIZANT for the management of postherpetic neuralgia was established in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, 12-week study eva luating the efficacy, safety, and dose response of 3 maintenance doses of HORIZANT (1,200, 2,400, and 3,600 mg/day, with 107, 82, and 87 patients in each dosing group, respectively). Patients greater than 18 years of age with a documented medical diagnosis of PHN of at least three months duration were enrolled. To ensure that patients had significant pain, randomized patients were required to have a minimum baseline 24-hour average Pain Intensity Numerical Rating Scale (PI-NRS) intensity score of at least 4.0 on the 11-point numerical PI-NRS, ranging from 0 (“no pain”) to 10 (“pain as bad as you can imagine”).
In this study, a total of 276 patients received HORIZANT while 95 patients received placebo. Following a 1-week baseline period during which patients were screened for eligibility, patients began a 1-week up-titration period followed by a 12-week maintenance treatment period, and then a 1-week down-titration period.
Treatment with HORIZANT statistically significantly improved the mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline at all doses tested. A benefit over placebo was observed for all 3 doses of HORIZANT as early as Week 1 and maintained to th |
