Table 1.
Demographic and clinical characteristics of patients at baseline (intent-to-treat population)
| Measure | De novo patientsa (N = 73) | Exposed patientsb (N = 29) | Between-group p-value |
|---|---|---|---|
| Age (years), Mean (SE) | 38.5 (1.70) | 36.8 (2.95) | 0.481 |
| Men, n (%) | 31 (42.5) | 14 (48.3) | 0.594 |
| Weight (kg) at inclusion, Mean (SE) | 74.8 (2.06) | 81.8 (4.01) | 0.223 |
| Duration since narcolepsy diagnosis (years) (SE) | 12.3 (1.56) | 13.8 (1.76) | 0.595 |
| QTc interval on EKG at screening, Mean (SE) | 405 (2.96) | 410.5 (5.35) | 0.291 |
| ESS score at inclusion, Mean (SE) | 17.6 (0.35) | 15.6 (0.54) | 0.004 |
| CUP patients sub group | 14.50 (0.8) | ||
| History of cataplexy, n (%) | 52 (71.2) | 23 (79.3) | 0.404 |
| History of treatments for narcolepsy – Stimulants prior inclusion, n (%) | |||
| Modafinil | 54 (74.0) | 26 (89.7) | |
| Methylphenidate | 41 (56.2) | 25 (86.2) | |
| Mazindol | 12 (16.4) | ||
| Dextroamphetamine | 2 (2.7) | 3 (10.3) | |
| History of treatments for cataplexy prior inclusion, n (%) | |||
| Sodium oxybate | 16 (21.9) | 11 (37.9) | |
| SSRI | 3 (4.1) | 2 (6.9) | |
| Venlafaxine | 5 (6.8) | 4 (13.8) | |
| Daily number of generalized cataplexy at inclusion (sleep diary), n | 58c | 13c | |
| Mean value (SE) | 0.25 (0.18) | 0.09 (0.09) | 0.682 |
| Daily number of partial cataplexy at inclusion (sleep diary), n | 58 | 13 | |
| Mean value (SE) | 0.64 (0.22) | 0.66 (0.40) | 0.970 |
| Multiple sleep latency test, n | 67 | 24 | |
| Mean sleep latency, minute (SE) | 5.3 (0.32) | 4.8 (0.53) | 0.454 |
| History of associated symptoms, n (%) | |||
| Hallucinations | 43 (58.9) | 17 (58.6) | 0.979 |
| Automatic behaviors | 33 (45.2) | 13 (44.8) | 0.972 |
| Dyssomnia | 37 (50.7) | 17 (58.6) | 0.469 |
| Sleep paralysis | 37 (50.7) | 13 (44.8) | 0.593 |
| Clinical general impression severity of narcolepsy at inclusion, n | 72 | 25 | |
| 3 = mildly ill, n (%) | 1 (1.4) | 3 (12.0) | 0.169 |
| 4 = moderately ill, n (%) | 10 (13.9) | 5 (20.0) | |
| 5 = markedly ill, n (%) | 23 (31.9) | 6 (24.0) | |
| 6 = severely ill, n (%) | 35 (48.6) | 11 (44.0) | |
| 7 = among the most extremely ill, n (%) | 3 (4.2) | - | |
| Quality of life (EQ-5D VAS score) at inclusion, Mean (SE) | 62.2 (1.92) | 74.8 (2.12) | <0.001 |
| Beck Depression Inventory – 13 Item Score at inclusiond, n | 71 | 25 | 0.013 |
| Mean (SE) | 4.8 (0.53) | 2.8 (0.58) | |
| Ongoing treatment for sleepiness or cataplexy at inclusion, n (%) | 26 (35.6) | 10 (34.5) | |
| Methylphenidate | 10 (13.7) | 3 (10.3) | |
| Modafinil | 8 (11.0) | 2 (6.9) | |
| Venlafaxine | 8 (11.0) | 1 (3.4) | |
| Sodium oxybate | 3 (4.1) | 4 (13.8) | |
| Mazindol | 1 (1.4) | 2 (6.9) | |
| Citalopram | 1 (1.4) | - | |
| Fluoxetine | 1 (1.4) | - | |
| Concomitant treatment for sleepiness or cataplexy during the trial, n (%) | 40 (54.8) | 14 (48.3) | |
| Methylphenidate | 18 (24.7) | 5 (17.2) | |
| Modafinil | 15 (20.5) | 3 (10.3) | |
| Venlafaxine | 12 (16.4) | 2 (6.9) | |
| Sodium oxybate | 6 (8.2) | 5 (17.2) | |
| Mazindol | 3 (4.1) | 1 (3.4) | |
| Escitalopram | 3 (4.1) | 2 (6.9) | |
| Paroxetine, Citalopram, Fluoxetine | 3 (4.1) | 2 (6.9) | |
| Clomipramine | 1 (1.4) | - |
Data are median (range), mean ± SE, or n (%). MSLT = Multiple Sleep Latency Test; EDS = Excessive Daytime Sleepiness; BDI = Beck Depression Inventory; ESS = Epworth Sleepiness Scale. Significant p-values are bolded.
aDe novo: patients naïve to pitolisant prior to this study.
bExposed: 13 patients having received pitolisant in previous trial or 16 patients already treated in CUP.
cNumber of patients for which the information was available (including patients without history of cataplexy).
dOne de novo patient was included despite a BDI score of 24 and item G > 0 (3 at screening; 1 at inclusion); this was a major deviation. Nevertheless, as the primary endpoint was safety, this patient was taken into account in the analysis.