First author, year [ref.] | Study type | Sample | Tests used | Results | Comments |
Schweitzer, 2019 [85] | OSA TONES 3 Phase 3 randomised double-blind placebo-controlled; 12 weeks solriamfetol once daily (37.5 mg/75 mg/150 mg/300 mg versus placebo) | 476 adults with OSA current or prior use of CPAP, MAD or surgery ESS ≥10, sleep latency on MWT <30 mins, usual night sleep ≥6hrs Randomisation stratified by adherence (>4 h) or non-adherence (<4 h) | Co-primary endpoints: change from baseline to 12 weeks in MWT and ESS Secondary endpoints: PGI-C and CGI-C | MWT: change from baseline compared with placebo (95% CI): 37.5 mg 4.5 (1.2–7.9) p=0.0086, 75 mg 8.9 (5.6–12.1) p<0.0001, 150 mg 10.97 (8.1–13.4), p<0.0001, 300 mg, 12.8 (10.0–15.6), p<0.0001 ESS: change from baseline compared with placebo (95% CI): 3.75 mg −1.9 (−3.4–−0.3), p=0.0161, 75 mg −1.7 (−3.2–−0.2) p=0.0233, 150 mg −4.5 (−5.7–−3.2), p<0.0001, 300 mg −4.7 (−5.9–−3.4), p<0.0001 | Good dose-dependent response in wakefulness as defined by MWT increase and reduction in ESS Best response with highest dose (300 mg) Dose response in cardiovascular physiological effects such as BP and heart rate with 300 mg showing small but statistically significant rise in BP (2.5 (0.4–4.6)) |
Strollo, 2019 [86] | OSA TONES 4 Phase 3 enriched randomised withdrawal study 2 weeks of solriamfetol dose 75, 150 or 300 mg versus placebo in withdrawal phase | 124 adults were randomised to withdrawal or continue on active drug following a screening (only those with improvement entered), titration and stable dose phase | Co-primary endpoints: change from baseline to 12 weeks in MWT and ESS Secondary endpoints: PGI-C and CGI-C | MWT during withdrawal phase difference from placebo mean (95% CI): 11.2 (7.8–14.6), p<0.0001 ESS during withdrawal phase difference from placebo mean (95% CI) −4.6 (−6.4–−2.8), p<0.0001 | Improvements in sleepiness were maintained compared to the group who were randomised to placebo (withdrawn) No rebound hypersomnia or withdrawal adverse events Enriched population including only those who had a positive response to the drug during the stable phase May not be the same level of response in the general population |
Malhotra, 2020 [87] | TONES 5 Long-term study (narcolepsy or OSA) 2 weeks of titration followed by maintenance phase At 6 months subgroups were randomised to solriamfetol or placebo and underwent 2-week withdrawal | 417 patients with OSA, 226 patients with narcolepsy in long-term follow-up phase 282 entered randomised withdrawal phase | Primary endpoint: change in ESS Secondary endpoint: change in PGI-C and CGI-C | Mean difference from placebo during withdrawal phase: −3.7 (−4.8–−2.65), p<0.0001 | Showed that the response is maintained longer term The effect was consistent across the narcolepsy and OSA groups |
Pépin, 2021 [89] | HAROSA 1 Phase 3 double-blind randomised placebo-controlled study 12 weeks of pitolisant at 3:1 versus placebo | 244 adult patients with OSA who were compliant with CPAP therapy | Primary endpoint: change in ESS Secondary endpoints: included OSLER test and EQ-5D as well as safety data | Mean difference from placebo (95% CI): –2.6 (–3.9––1.4), p<0.001 | Significant reduction in subjective and objective sleepiness when used as an adjunct to CPAP therapy There were no safety concerns with good improvements in patient- and physician-reported health outcomes |
Dauvilliers, 2020 [90] | HAROSA 2 Phase 3 double-blind randomised placebo-controlled study 12 weeks of pitolisant at 5/10/20 mg (3:1) versus placebo | 268 adult patients with OSA who were unable to use CPAP therapy | Primary endpoint: change in ESS Secondary endpoints: included OSLER test and EQ-5D as well as safety data | Mean difference from placebo (95% CI): −2.8 (−4.0–−1.5), p<0.001 | Significant response in ESS in this group and safety data showing that there were no significant adverse events in non-CPAP users |
BP: blood pressure; CGI-C: clinical global impression of change; CPAP: continuous positive airway pressure; EQ-5D: European Quality of Life–five dimensions; ESS: Epworth Sleepiness Scale; MAD: mandibular advancement device; MWT; maintenance of wakefulness test; OSLER: Oxford Sleep Resistance; PGI-C: patient global impression of change.