Table 2.
Effects of oxybate treatment on PSG measures of DNS
| Twice-nightly oxybate (SXB) | Once-nightly oxybate (SXB-ER) | ||||
|---|---|---|---|---|---|
| SXB trial 1 | SXB trial 2 | Pediatric SXB trial | SXB trial 3 | REST-ON trial | |
| PSG measures of DNS | Median change from baseline to 8 weeks | Median change from baseline to 4 weeks (6 g) or 8 weeks (9 g) | Median change from baseline to end of study (individual doses) | Mean at 4 weeks (4.5 g), 6 weeks (6 g), 8 weeks (7.5 g), or 10 weeks (9 g) | LSMD vs placebo at week 3 (6 g), week 8 (7.5 g), or week 13 (9 g) |
| TST, min |
Increased Placebo: 0.3 SXB 4.5 g: 0 SXB 6 g: 13.0 SXB 9 g: 18.0† |
Not significant Placebo: − 5.5 SXB 6 g: − 5 Placebo: − 0.5 SXB 9 g: − 4.5 |
– |
Not significant (4.5 g decreased) Baseline: 383.4 SXB 4.5 g: 364.8* SXB 6 g: 363.0 SXB 7.5 g: 374.1 SXB 9 g: 380.8 |
– |
| WASO, min |
Decreased Placebo: 2.0 SXB 4.5 g: − 5.8 SXB 6 g: − 3.8 SXB 9 g: − 22.0† |
– | – | – | – |
| N1, min (except pediatric data) |
Decreased Placebo: − 2.3 SXB 4.5 g: − 9.5 SXB 6 g: − 13.5††† SXB 9 g: − 22.5††† |
Decreased Placebo: 3.25 SXB 6 g: − 9.5 Placebo: 1.5 SXB 9 g: − 16††† |
Decreased SXB-naive: − 4.6% Taking SXB at study entry: − 0.6% |
Not significant Baseline: 74.8 SXB 4.5 g: 72.3 SXB 6 g: 68.1 SXB 7.5 g: 69.4 SXB 9 g: 62.6 |
Decreased SXB-ER 6 g: − 5.9† SXB-ER 7.5 g: − 11.0††† SXB-ER 9 g: − 13.4††† |
| N2, min |
Not significant Placebo: 3.5 SXB 4.5 g: 9.5 SXB 6 g: 13.0 SXB 9 g: 31.5 |
Not significant Placebo: − 5.25 SXB 6 g: 0.5 Placebo: − 8.25 SXB 9 g: 3.5 |
No change Values not reported |
Not significant Baseline: 217.8 SXB 4.5 g: 216.9 SXB 6 g: 216.9 SXB 7.5 g: 224.1 SXB 9 g: 238.0 |
Not significant SXB-ER 6 g: − 6.6 SXB-ER 7.5 g: 3.6 SXB-ER 9 g: − 13.5 |
| SWS, min (except pediatric data) |
Increased Placebo: 0 SXB 4.5 g: 3.0† SXB 6 g: 21.0††† SXB 9 g: 52.5††† |
Increased Placebo: 0 SXB 6 g: 11† Placebo: 0 SXB 9 g: 43.5††† |
Increased SXB-naive: 12.6% Taking SXB at study entry: − 1.0% |
Increased Baseline: 3.0 (1st half), 0.6 (2nd half) SXB 4.5 g: 3.5 (1st half), 0.7 (2nd half) SXB 6 g: 5.5 (1st half), 4.5 (2nd half) SXB 7.5 g: 9.8 (1st half), 4.5* (2nd half) SXB 9 g: 14.2 (1st half), 12.6* (2nd half) |
Increased SXB-ER 6 g: 22.1††† SXB-ER 7.5 g: 26.8††† SXB-ER 9 g: 38.4††† |
| REM, min (except pediatric data) |
Decreased Placebo: − 1.0 SXB 4.5 g: − 6.0 SXB 6 g: − 7.0 SXB 9 g: − 22.0† |
Decreased Placebo: 6.25 SXB 6 g: − 14.5†† Placebo: 10 SXB 9 g: − 38.5††† |
Decreased SXB-naive: − 6.0% Taking SXB at study entry: not reported |
Decreased Baseline: 31.2 (1st half), 56.0 (2nd half) SXB 4.5 g: 29.7 (1st half), 43.5* (2nd half) SXB 6 g: 26.3 (1st half), 42.7*** (2nd half) SXB 7.5 g: 31.3 (1st half), 34.9*** (2nd half) SXB 9 g: 22.9 (1st half), 30.5*** (2nd half) |
Decreased SXB-ER 6 g: − 16.7††† SXB-ER 7.5 g: − 27.2††† SXB-ER 9 g: − 24.5††† |
| Shifts from N2/N3/REM to N1/wake |
Decreased (LSM change from baseline in shifts per hour) Placebo: − 0.8 SXB 4.5 g: − 1.7 SXB 6 g: − 2.7† SXB 9 g: − 4.4††† |
Decreased (LSM change from baseline in shifts per night) Placebo: − 0.6 SXB 9 g: − 16.5††† |
– | – |
Decreased (LSMD change from baseline in shifts per night to wake or N1 from N1, N2, N3, and REM) SXB-ER 6 g: − 11.0††† SXB-ER 7.5 g: − 17.7††† SXB-ER 9 g: − 22.6††† |
| Shifts from N2/N3 to N1/wake |
Decreased (LSM change from baseline in shifts per hour) Placebo: − 0.3 SXB 4.5 g: − 0.9 SXB 6 g: − 1.7† SXB 9 g: − 3.1††† |
– | – | – | |
| Shifts from REM to N1/wake |
Decreased (LSM change from baseline in shifts per hour) Placebo: − 1.9 SXB 4.5 g: − 3.8 SXB 6 g: − 5.0 SXB 9 g: − 7.6† |
Decreased (LSM change from baseline in shifts per night) Placebo: − 0.6 SXB 9 g: − 6.0††† |
– | – | |
| Arousals | – | – |
Decreased SXB-naive: − 43.0 Taking SXB at study entry: − 1.0 |
– |
Decreased SXB-ER 6 g: − 11.3† SXB-ER 7.5 g: − 19.4††† SXB-ER 9 g: − 23.7††† |
| Awakenings |
Decreased Placebo: − 0.5 SXB 4.5 g: − 5.0 SXB 6 g: − 8.0†† SXB 9 g: − 12.0†† |
Decreased Placebo: − 0.5 SXB 6 g: − 1 Placebo: − 0.5 SXB 9 g: − 6†† |
No change SXB-naive: − 4.0 awakenings Taking SXB at study entry: 1.5 awakenings |
Decreased Baseline: 50.2 SXB 4.5 g: 50.0 SXB 6 g: 45.1 SXB 7.5 g: 37.3*** SXB 9 g: 37.8** |
– |
| Patient-reported sleep quality |
Improved (4-point Likert scale)a Placebo: − 0.10 SXB 4.5 g: − 0.41† SXB 6 g: − 0.31† SXB 9 g: − 0.46††† |
Improved (LSM change from baseline on question 6 of the PSQI) Placebo: − 0.07 SXB 9 g: − 0.52††† |
– |
Improved (Self-reported degree of change) Baseline: 0% (much), 14% (somewhat) SXB 4.5 g: 19% (much), 57% (somewhat) SXB 6 g: 24% (much), 67% (somewhat) SXB 7.5 g: 24% (much), 62% (somewhat) SXB 9 g: 24% (much), 57% (somewhat) |
Improved (Visual analog scale from 0–100)b SXB-ER 6 g: 7.0††† SXB-ER 7.5 g: 9.9††† SXB-ER 9 g: 10.4††† |
DNS disrupted nighttime sleep, LSM least squared mean, LSMD least squared mean difference, N1/2 stage 1/2 non-rapid eye movement sleep, ns not significant, PSG polysomnography, REM rapid eye movement, S3/S4 stage 3/4, SWS slow-wave sleep, SXB sodium oxybate, SXB-ER sodium oxybate for extended release, TST total sleep time, WASO wake after sleep onset
aAssessed with 4-point Likert-type scale (0, excellent; 1, good; 2, fair; 3, poor)
bBaseline scores were 53.8 and 55.9 in ON-SXB and placebo groups, respectively
†P < 0.05 vs placebo. ††P < 0.01 vs placebo. †††P < 0.001 vs placebo. *P < 0.05 vs baseline. **P < 0.01 vs baseline. ***P < 0.005 vs baseline. – denotes a variable not assessed in this trial. No statistical testing was performed in the pediatric trial