Table 1.
Efficacy of PIT clinical studies in narcolepsy
| Study | Type | Phase | Study design | Endpoint | PIT dosage | Number of subjects | Duration | Tool | Efficacy | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| P05-03 | Proof-of-concept study | II | SB, PC, MC | Action on vigilance in narcolepsy | 40 mg | 22 (14 M, 8 F) | 1 week PLC, 1 week PIT | ESS | PIT −5.9, p<0.0006 versus PLC −1.0 p>0.05 | Lin et al,31 2008 |
| P07-03 Harmony I | P | III | DB, R, PC, AC (MOD), MC | Superiority versus PLC (3 points ESS) Non-inferiority versus MOD Cataplexy | PIT 10–40 mg | 32 PIT 33 MOD 30 PLC |
3 weeks flexible dose + 5 weeks stable dose | ESS MWT |
ESS: PIT −5.8 MOD −6.9 PLC −3.4 Superiority to PLC confirmed by MWT Significant reduction in cataplexy rate Responders 71% |
Dauvilliers et al,16 2013 |
| P09-15 Harmony Ibis | P | III | DB, R, PC, AC | Superiority versus PLC Non-inferiority versus MOD Cataplexy |
PIT 10–20 mg | 66 PIT 65 MOD 32 PLC |
3 weeks flexible dose + 5 weeks stable dose | ESS MWT |
ESS: PIT −4.6 MOD −7.8 PLC −3.6 Confirmed non-inferiority to PLC Responders 66.7% Failed superiority to PLC and MOD and cataplexy |
Kollb-Sielecka et al,44 2017 |
| P06-06 | O | II | OL, MC | Initial tolerability | 10, 20, and40 mg | 26 (21 M, 5 F) | 9 months | ESS | −4.8 (1 month FU) −5.3 (3 months FU) −6.9 (9 months FU) |
EMA Waki Report,34 2015 |
| P09-10 | O | III | OL, MC | Long-term tolerability | 5–40 mg | 102 (45 M, 57 F) partially from RCT Harmony I, II, and Ibis | 12 months | ESS | −4.3, similar to RCT, but biased in efficacy due to clinical and drug heterogeneity | EMA Waki Report,34 2015 |
| P07-07 Harmony II | RCT | II | DB, R, PC, PG | Efficacy versus MOD | 10–40 mg | 14 (8 M, 6 F) | 8 weeks | ESS | Study not completed | EMA Waki Report,34 2015 |
| P10-01 Harmony IV | RCT | III | DB, R, PC | Efficacy in add-on to oxybate | 10–40 mg | 26 PIT, 22 PLC (34 M, 14 F) | 8 weeks | ESS MWT |
No differences between PIT and PLC | HAS French Regulatory Agency,47 2016 |
| P11-05 Harmony CTP | RCT | III | DB, R, PC, PG | Anti-cataplexy effect | 20–40 mg | 54 PIT, 51 PLC | 8 weeks | WCR ESS MWT |
Significant reduction in WCR, ESS, and MWT, both with 20–40 mg PIT versus PLC Responders 68.6% |
Szakacs et al,43 2017 |
Abbreviations: AC, active controlled; DB, double blind; ESS, Epworth Sleepiness Scale; FU, follow-up; MC, multicentric; MOD, modafinil; MWT, Maintenance Wakefulness Test; O, open study; OL, open label; P, pivotal study; PC, placebo controlled; PG, parallel group; PIT, pitolisant; PLC, placebo; R, randomized; RCT, randomized controlled trial; SB, single blind; WCR, weekly cataplexy rate.