tswere apparent at Week 1 and consistent with the results at Week 12. The change on percentageof subjects reported as improved by PGIc was also statistically significant compared withplacebo. Examination of subgroups by age, race, and sex did not suggest differences in response.
At Week 12, 37.5 mg, 75 mg, and 150 mg of SUNOSI all demonstrated improvements inwakefulness compared to placebo as assessed in test sessions 1 (approximately 1 hour post-dose)through 5 (approximately 9 hours post-dose) of the MWT (Figure 3). Nighttime sleep asmeasured with polysomnography was not affected by the use of SUNOSI in Study 2. Patients’compliance with a primary OSA therapy device was similar across the placebo and SUNOSItreatment groups at baseline, and did not change during the 12-week study period in anytreatment group.
Figure 3: Maintenance of Wakefulness Test Improvements in Test Sessions 1through 5 in Patients with OSA in Study 2 at Week 12
Table 6: Efficacy Results for Maintenance of Wakefulness Test (minutes) in Patients with
Narcolepsy (Study 1) and OSA (Study 2)
Indication/
Study Treatment Group (N) Baseline
Mean (SD)
LS Mean
Change from
Baseline at
Week 12 (SE)
Difference from
Placebo (95% CI)
Narcolepsy
STUDY 1
Placebo (58) 6.2 (5.7) 2.1 (1.3) -
SUNOSI 75 mg (59) 7.5 (5.4) 4.7 (1.3) 2.6 (-1.0, 6.3)
SUNOSI 150 mg* (55) 7.9 (5.7) 9.8 (1.3) 7.7 (4.0, 11.3)
OSA
STUDY 2
Placebo (114) 12.6 (7.1) 0.2 (1.0) -
SUNOSI 37.5 mg* (56) 13.6 (8.1) 4.7 (1.4) 4.5 (1.2, 7.9)
SUNOSI 75 mg* (58) 12.4 (6.9) 9.1 (1.4) 8.9 (5.6, 12.4)
SUNOSI 150 mg* (116) 12.5 (7.2) 11.0 (1.0) 10.7 (8.1, 13.4)
SD = standard deviation; SE = standard error; LS Mean = least square mean; CI = confidence intervalMaximum possible MWT score is 40 minutes. A positive change represents improvement.
Difference from Placebo = LS Mean Difference between change from baseline between active drug and placebo.
* Dose that was statistically significantly superior to placebo after adjusting for multiplicity.
Table 7: Efficacy Results for Epworth Sleepiness Scale in Patients with Narcolepsy (Study 1) and OSA (Study 2)
Indication/
Study Treatment Groups (N) Baseline Score
Mean (SD)
LS Mean
Change from
Baseline at
Week 12 (SE)
Difference from
Placebo (95% CI)
Narcolepsy
STUDY 1
Placebo (58) 17.3 (2.9) -1.6 (0.7) -
SUNOSI 75 mg (59) 17.3 (3.5) -3.8 (0.7) -2.2 (-4.0, -0.3)
SUNOSI 150 mg* (55) 17.0 (3.6) -5.4 (0.7) -3.8 (-5.6, -2.0)
OSA
STUDY 2
Placebo (114) 15.6 (3.3) -3.3 (0. 5) -
SUNOSI 37.5 mg* (56) 15.1 (3.5) -5.1(0.6) -1.9 (-3.4, -0.3)
SUNOSI 75 mg* (58) 15.0 (3.5) -5.0 (0.6) -1.7 (-3.2, -0.2)
SUNOSI 150 mg* (116) 15.1 (3.4) -7.7 (0.4) -4.5 (-5.7, -3.2)
SD = standard deviation; SE = standard error; LS Mean = least square mean; CI = confidence intervalScores range from 0 to 24 with higher scores indicating more severe sleepiness. A negative change represents improvement.
Difference from placebo = LS mean difference between change from baseline between SUNOSI and placebo.
* Dose that was statistically significantly superior to placebo after adjusting for multiplicity.
14.3 Maintenance of Efficacy in Narcolepsy and OSA
The maintenance of effect of SUNOSI in improving wakefulness and reducing excessivedaytime sleepiness in patients with narcolepsy and OSA was assessed in two
randomized-withdrawal, placebo-controlled studies, Study 3 (NCT02348619) and Study 4(NCT02348632).
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