udy 3 was a 6-week, multi-center, double-blind, placebo-controlled, randomized-withdrawalstudy in 174 adult patients with a diagnosis of OSA. The co-primary efficacy endpoints werechange from the beginning to the end of the randomized withdrawal period in MWT and ESS.
During a 2-week, open-label titration phase, patients were started on SUNOSI 75 mg once daily,and were titrated to the maximum tolerable dose between 75 mg and 300 mg per day (two timesthe maximum recommended daily dose). Patients were continued on this dose for a 2-weekstable-dose phase. At the end of the stable-dose phase, 124 patients who reported “much” or“very much” improvement on the PGIc and who showed improvements on the MWT and ESSentered a double-blind withdrawal phase and were randomized 1:1 to either continue SUNOSI atthe dose received in the stable-dose phase or switch to placebo. Compared to patients whoremained on SUNOSI, patients randomized to placebo experienced statistically significantworsening of sleepiness as measured by the MWT and ESS (Table 8).
Study 4 was a 52-week, open-label study in 638 patients with either narcolepsy or OSA who hadcompleted a prior trial. During a 2-week, open-label titration phase, patients were started onSUNOSI 75 mg once daily, and were titrated to the maximum tolerable dose between 75 mg and300 mg per day (two times the maximum recommended daily dose). Patients remained on thisdose during a subsequent open-label treatment period of either 38 (for patients previouslyenrolled in Study 1 or Study 2) or 50 (all others) weeks. A 2-week randomized-withdrawalperiod was incorporated into the study. After 6 months of stable-dose treatment, 282 patients (79with narcolepsy; 203 with OSA) entered the randomized-withdrawal period. Patients wererandomized 1:1 to either continue to receive SUNOSI at the dose received in the maintenance
phase or to switch to placebo. The primary efficacy endpoint was change from the beginning tothe end of the randomized-withdrawal period in ESS. Compared to patients who remained onSUNOSI, patients randomized to placebo experienced statistically significant worsening ofsleepiness as measured by the ESS (Table 8).
Table 8: Efficacy Results from Randomized Withdrawal Studies in Patients with
Narcolepsy and OSA in Studies 3 and 4
Indication/
Study Endpoint Treatment
Groups (N)
Beginning of
Randomized
Withdrawal
Period
(Baseline)
Mean (SD)
LS Mean
Change
from
Baseline
(SE)
Difference from
Placebo (95%
CI)
OSA
STUDY 3
MWT (minutes) Placebo (62)
SUNOSI* (60)
29.0 (9.9)
31.7 (9.2)
-12.1 (1.3)
-1.0 (1.4) 11.2 (7.8, 14.6)
ESS Score Placebo (62)
SUNOSI* (60)
5.9 (3.8)
6.4 (4.4)
4.5 (0.7)
-0.1 (0.7) -4.6 (-6.4, -2.8)
OSA and
Narcolepsy
STUDY 4
ESS Score Placebo (141)
SUNOSI* (139)
7.8 (5.0)
7.3 (5.3)
5.3 (0.4)
1.6 (0.4) -3.7 (-4.8, -2.7)
SD = standard deviation; SE = standard error; LS Mean = least square mean; CI = confidence intervalFor MWT, maximum possible score is 40 minutes; negative changes indicate worsening.
For ESS, scores range from 0 to 24; positive changes indicate worsening.
* Statistically significantly superior to placebo after adjusting for multiplicity.
16 HOW SUPPLIED / STORAGE AND HANDLING
16.1 How Supplied
SUNOSI is packaged in 30-count and 100-count white, high density polyethylene (HDPE)
bottles.
SUNOSI tablets, 75 mg - dark |
