Solriamfetol shows promise for excessive daytime sleepiness in OSA
The selective dopamine and norepinephrine reuptake inhibitor solriamfetol improves wakefulness in patients with obstructive sleep apnoea (OSA) who have previously received primary treatment for OSA, a phase III study shows.
“The ability to treat excessive sleepiness [ES] effectively is an important component of OSA management because ES can persist despite primary OSA therapy,” said the researchers, who noted that ES persists in an estimated 12–65 percent of patients despite treatment with continuous positive airway pressure therapy.
The phase III trial comprised three phases: 2 weeks of clinical titration followed by 2 weeks of stable dosing, after which 124 participants (aged 18–75 years, mean age 56 years) with OSA who met the criteria for improvements on the PGIC*, MWT**, and ESS*** entered the double-blind randomized withdrawal phase whereby they were randomized 1:1 to placebo or solriamfetol for 2 weeks. [Chest 2018;doi:10.1016/j.chest.2018.11.005]
Among the participants who met the criteria for randomization phase, objective wakefulness scores — as indicated by MWT mean sleep latency — more than double from 12–13 minutes at baseline to 29.0–31.7 minutes at week 4 (after stable dosing phase). Subjective wakefulness also improved, as shown by a decrease from 15.3–16.0 at baseline to approximately 6 at week 4 on the ESS scores.
During the randomized withdrawal phase (from weeks 4–6), patients who continued treatment with solriamfetol had sustained improvements while those who switched to placebo worsened in the coprimary endpoints of MWT mean sleep latency (least squares [LS] mean changes, -1.0 vs -12.1 minutes; p<0.0001) and ESS score (LS mean changes, -0.2 vs 4.5; p<0.0001).
“Neither MWT mean sleep latency nor ESS score returned to the baseline value in the placebo group, suggesting a carryover treatment effect of solriamfetol and the absence of rebound hypersomnia [after abrupt discontinuation of solriamfetol] during this 2-week period,” the researchers pointed out.
“Reductions in ES may be expected to translate into patient-centred benefits,” they added, noting that global improvements in the solriamfetol group were similarly robust regardless of whether these were rated by participants on the PGIC or by physicians on CGI-C^.
Fewer patients in the solriamfetol group worsened on the PGIC (20 percent vs 50 percent; p=0.005) and the CGI-C (21.7 percent vs 59.0 percent; p<0.001) compared with the placebo group. Participant-reported daily function as assessed using the FOSQ-10^^ was also significantly better in the solriamfetol group vs placebo at week 6 (LS mean changes, -0.2 vs -1.3; p<0.05).
The most common adverse events during the dose titration phase included headache (9.8 percent), dry mouth (6.9 percent), nausea (6.9 percent), dizziness (5.7 percent), and insomnia (5.7 percent); while nasopharyngitis was the most common event, occurring in 4.8 percent of patients in the solriamfetol group vs none in the placebo group.
“The current trial suggests the potential for greater efficacy of solriamfetol relative to [other] wake-promoting agents … [and] the safety profile was consistent with those of other solriamfetol studies,” said the researchers.
As the study duration was short, principal investigator Dr Susan Redline from Brigham and Women's Hospital in Boston, Massachusetts, US, cautioned that the long-term effects of the medication is unknown, in particular on heart health as wake-promoting agents do not treat the cardiovascular complications of sleep apnoea.