Solriamfetol 150mg tablets

Background: Obstructive sleep apnoea (OSA) is a common chronic respiratory disease associated with a high burden of disabilities related to sleepiness and reduced quality of life. Despite first-line treatment with continuous positive airway pressure (CPAP) therapy, many patients experience residual excessive daytime sleepiness (EDS). The aim of this study is to compare the relative efficacy and safety of medications authorised for this indication in Europe and/or the United States (modafinil/armodafinil, solriamfetol, and pitolisant) for OSA. Methods: In this systematic review and network meta-analysis, randomised controlled trials (RCTs) that compared the efficacy and safety of authorised medications for adult patients with OSA were identified by literature searches of PubMed, Embase and ClinicalTrials.gov databases (up to 12 June 2024). The primary efficacy endpoint was combined Epworth Sleepiness Scale (ESS) and Oxford Sleep Resistance (OSLER)/Maintenance of Wakefulness Test (MWT) Z-scores. Quality of life (QoL), overall and specific cardiovascular safety, and benefit-risk ratios were calculated. The study was registered with PROSPERO: CRD42023434640. Findings: Of 4017 studies identified, a total of 20 RCTs involving 4015 patients were included. Analysis of combined subjective (ESS) and objective (OSLER/MWT) efficacy outcome Z-scores showed that solriamfetol (150 mg; effect size [ES] = 0.66 [95% CI: 0.36, 0.96]), pitolisant (20 mg; ES = 0.66 [95% CI: 0.44, 0.88]), and modafinil (200 mg; ES = 0.54: [95% CI: 0.33, 0.74]); 400 mg; ES = 0.54 [95% CI: 0.42, 0.65]) had a clinically meaningful improvement in efficacy. P-scores ranked placebo, then pitolisant, modafinil 200 mg, modafinil 400 mg and solriamfetol for overall safety; and pitolisant, then solriamfetol, modafinil 400 mg and modafinil 200 mg for benefit-risk ratio. Interpretation: Pitolisant, solriamfetol and modafinil had comparable efficacy for maintaining wakefulness in patients with OSA. Pitolisant had a better safety profile and benefit-risk ratio compared with solriamfetol and modafinil. The overall and cardiovascular safety risk ratios suggest that pitolisant might be the best candidate for patients with OSA with multiple cardiovascular comorbidities. Funding: Bioprojet.

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Residual sleepiness can occur in adult patients with obstructive sleep apnea (OSA) despite adequate treatment with continuous positive airway pressure (CPAP). Various wake-promoting agents (WPAs) have been shown to reduce residual sleepiness in CPAP-treated patients with OSA. This systematic review and network meta-analysis aimed to compare the efficacy and safety of WPAs in this setting. We searched MEDLINE, Scopus, and ClinicalTrials.gov up to 9 January 2025 for randomized controlled trials (RCTs) examining WPAs for treating sleepiness in patients with OSA. Included were all RCTs that explored the efficacy and/or safety of any approved WPAs (i.e., modafinil, armodafinil, solriamfetol, or pitolisant) in patients with OSA (aged $$\ge$$ 18 years) treated with CPAP but who are still sleepy [Epworth sleepiness scale (ESS) score ≥10]. Studies that were conducted in patients whose comorbidities cause daytime somnolence [i.e., psychiatric conditions (other than depression), other sleep disorders, medical or surgical conditions], open label extension studies, and studies published in a language other than English were excluded. The primary outcomes included ESS, maintenance of wakefulness test (MWT), and adverse events. Two authors independently assessed the risk of bias using the revised Cochrane risk-of-bias tool for randomized trials 2.0. In total, 14 RCTs studying four WPAs (total N = 2969) including modafinil (six RCTs; 200–400 mg/day), armodafinil (four RCTs; 150–250mg/day), solriamfetol (two RCTs; 37.5–300 mg/day), and pitolisant (two RCTs; 5–40 mg/day) were included. Solriamfetol, modafinil, and armodafinil were efficacious in reducing subjective sleepiness as measured by ESS [mean difference (95% confidence interval) at $$\le$$ 4 weeks: −3.84 (−5.60, −2.07), −2.44 (−3.38, −1.49), and −2.41 (−3.60, −1.21) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: −4.11 (−6.14, −2.08), −2.88 (−3.85, −1.91), −2.46 (−3.68, −1.24) for solriamfetol, armodafinil, and modafinil, respectively] and clinical global impression of change, as well as the objective MWT [at $$\le$$ 4 weeks: 11.66 min (9.70, 13.61), 3.61 min (2.48, 4.73), and 2.52 min (1.27, 3.76) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: 10.34 min (4.16, 16.52) for solriamfetol]. Pitolisant showed later improvements in ESS [at > 4 weeks: −2.70 (−3.66, −1.73)], with limited data on MWT. Sensitivity analyses restricted to U.S. Food and Drug Administration-approved solriamfetol dosages (37.5–150 mg/day) still showed higher efficacy, but lower anxiety risk. Among all WPAs, solriamfetol demonstrated the highest efficacy on ESS and MWT, with the latter being significant. Modafinil demonstrated the best clinician impression, albeit not statistically significant. All four WPAs were associated with a low risk of serious or adverse events. PROSPERO registration number, CRD42022359237

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Background: Obstructive sleep apnoea (OSA) is a prevalent chronic condition that is associated with cardiometabolic and neurocognitive complications. While continuous positive airway pressure (CPAP) remains the first-line therapy, suboptimal adherence limits its effectiveness, highlighting the need to evaluate alternatives such as mandibular advancement devices (MADs), hypoglossal nerve stimulation (HNS), physical activity, different modalities of weight loss management including glucagon-like peptide-1 (GLP-1) agonists and combination therapies. Methods: We conducted an umbrella review to synthesise high-level evidence from meta-analyses of randomised controlled trials (RCTs) evaluating the efficacy, adherence, and safety of therapies used in patients with OSA. A comprehensive search was performed in PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews covering the period from January 1, 2017, to July 5, 2025. Eligible studies were meta-analyses published in English assessing interventions targeting key OSA outcomes, including changes in apnoea-hypopnoea index (AHI), Epworth Sleepiness Scale (ESS), quality of life (QoL), blood pressure (BP), treatment adherence, and safety. When multiple meta-analyses addressed the same intervention-outcome pair, the one including the highest number of RCTs was retained. Two reviewers independently screened studies and extracted data. Methodological quality was assessed using the AMSTAR 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Meta-analyses published in languages other than English, those focusing on paediatric populations or interventions outside the scope of conventional OSA management, and meta-analyses that did not report any of the pre-specified outcomes/interventions of interest were excluded. The review protocol was registered in PROSPERO (CRD42023420729) and the Open Science Framework (https://osf.io/2jvsx). Findings: A total of 5571 meta-analyses were identified. Of these, 34 met the inclusion criteria, encompassing 230 RCTs and 36,353 participants (n = 26,058 [72.3%] male). GRADE assessment showed that 12 meta-analyses (35%) had evidence that was of low certainty, 23 (68%) provided moderate-certainty evidence, and only one (3%) provided evidence that was of high certainty. CPAP was the most effective treatment for reducing AHI (mean difference [MD] -30.7 events/h; standardised mean difference [SMD] -1.65, 95% confidence interval [CI] -1.87 to -1.43; low-certainty evidence), followed by GLP-1 receptor agonists (tirzepatide: MD -21.86 events/h; SMD -0.84, 95% CI -1.01 to -0.68; moderate-certainty evidence) and MADs (MD -11.91 events/h; SMD -0.73, 95% CI -14.25 to -9.75; low-certainty evidence). CPAP, wake stimulants, HNS, and myofunctional therapy significantly reduced daytime sleepiness (ESS score SMDs of -0.80 to -0.88; moderate-certainty evidence except for pitolisant and solriamfetol, which were supported by high-certainty evidence). Physical activity led to the greatest improvements in QoL (SMD 1.3, 95% CI 0.58 to 2.02; moderate-certainty evidence), while CPAP also showed modest benefits (SMD 0.16, 95% CI 0.11 to 0.21; critically low-certainty evidence). Interpretation: This umbrella review identified CPAP as the most effective intervention for reducing AHI and daytime sleepiness in patients with OSA, while physical activity yielded the greatest improvements in quality of life. Data on safety, long-term adherence, and combination therapies remain scarce, underscoring the need for more comparative and longitudinal research to support personalised treatment strategies. Data need to be interpreted in the context of several limitations, including those relating to the meta-analysis inclusion criteria and the quality of data in the meta-analyses themselves. Funding: None.

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BACKGROUND: As a rare sleep disorder, narcolepsy is treated with various therapeutic options. This article systematically analyzes the efficacy and safety of novel approved wake-promoting drugs. METHODS: Randomized controlled trials (RCTs) for patients with narcolepsy and treated with approved interventions were searched. Outcome measures included Epworth sleepiness scale (ESS) score, mean latency in the maintenance of wakefulness test (MWT), cataplexy frequency, number of subjects with ESS scores < 10, standard deviation of lane position (SDLP) score, and adverse events (including anxiety, dizziness). This paper was registered in INPLASY (INPLASY2024120052). RESULTS: The final analysis included 13 RCTs with four drugs involved: modafinil/armodafinil, sodium oxybate (SXB), pitolisant, and solriamfetol, at different dosages or combinations. All drugs were effective in treating narcolepsy compared to placebo. Solriamfetol 300 mg was more effective than other treatments in reducing ESS scores (MD = -4.74, 95%CI: -6.51,-2.97) and prolonging sleep latency (MD = 10.82 min, 95%CI: 6.99, 14.31). Several novel wake-promoting drugs did not show significant differences in improving cataplexy frequency, the number of people with ESS scores < 10, and SDLP scores. The novel wake-promoting drugs compared in this article could improve adverse effects, but some drugs showed an elevated likelihood of some adverse effects compared to controls or other drugs. Compared to placebo, SXB yielded the highest risk of gastrointestinal adverse effects such as diarrhea [8.53, (1.14,263)] and vomiting [29.5, (2.46,1.46e+03)], pitolisant induced the highest risk of nausea [4.22e+08, (4.09,1.26e+32)], and SXB+modafinil had the highest risk of dizziness [7.67, (1.01,58.7)]. There were no considerable differences among drugs in other adverse effects. CONCLUSION: All of the approved new wake-promoting drugs are effective in controlling narcolepsy symptoms with acceptable adverse effects. Trial Registration The study was prospectively registered in the INPLASY database (INPLASY2024120052).

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BACKGROUND: OSA causes episodes of fragmented sleep and intermittent hypoxia and leads to excessive daytime sleepiness (EDS). Deficits in cognitive function are a troublesome symptom in patients with OSA and EDS. RESEARCH QUESTION: How does solriamfetol affect cognitive function in patients with cognitive impairment associated with OSA and EDS? STUDY DESIGN AND METHODS: Solriamfetol's Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-Controlled Study (SHARP) was a phase IV, randomized double-blind placebo-controlled crossover trial. Participants (N = 59) were randomized to receive placebo or solriamfetol (75 mg/d for 3 days, then 150 mg/d) for 2 weeks, with crossover separated by a 1-week washout period. Efficacy measures included the Coding subtest, comparable to the Digit Symbol Substitution Test (DSST), of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the British Columbia Cognitive Complaints Inventory (BC-CCI), the Patient Global Impression of Severity (PGI-S), and the Epworth Sleepiness Scale (ESS). The primary end point was change from baseline in average postdose DSST RBANS scores. Secondary end points were changes from baseline in BC-CCI, PGI-S, ESS, and DSST RBANS scores at 2, 4, 6, and 8 hours' postdose. Safety was monitored by assessment of treatment-emergent adverse events. RESULTS: Solriamfetol was shown to significantly improve postdose average DSST RBANS scores compared with placebo (P = .009; effect size [Cohen's d], 0.37). When evaluated at each 2-hour time point, cognitive function was significantly improved at 2, 6, and 8 hours after dosing (all, P < .05). During solriamfetol treatment, there were significant improvements in BC-CCI (P = .002; d = 0.45), PGI-S (P = .034; d = 0.29), and ESS (P = .004; d = 0.40) compared with placebo. The most common treatment-emergent adverse events were nausea (7%) and anxiety (3%). INTERPRETATION: SHARP showed that solriamfetol can improve objective and subjective measures of cognitive function in patients with cognitive impairment associated with OSA and EDS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04789174; URL: www. CLINICALTRIALS: gov and EudraCT; No.: 2020-004243-92; URL: https://eudract.ema.europa.eu.

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BACKGROUND: Solriamfetol is a dopamine and norepinephrine reuptake inhibitor (DNRI) indicated for the treatment of excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA). The current study aims to evaluate effects of solriamfetol among participants with different adherence to primary OSA therapy using data from a randomized clinical trial conducted among Chinese participants. METHODS: Participants were 1:1 randomized to placebo or solriamfetol (up to 150 mg/day) for 12 weeks (stratified by adherence to primary OSA therapy). The coprimary endpoints were change from baseline in mean sleep latency of maintenance of wakefulness test (MWT) and Epworth Sleepiness Scale (ESS) at week 12 in the full analysis set. Use of primary OSA therapy and safety were also evaluated. RESULTS: At baseline, of all participants, around 50 % were adherent, 20 % were non-adherent and 30 % were not on primary OSA therapy, respectively. In all subgroups, solriamfetol treatment was associated with significant or numerical improvement in MWT sleep latency or ESS (LS mean difference vs. placebo, p < 0.05 except ESS in non-adherence to primary therapy subgroup). Use of primary OSA therapy was stable throughout the 12-week study. Solriamfetol was well tolerated and the most common TEAEs included metabolism and nutrition disorders, upper respiratory tract infection, dizziness, hypertension and elevated blood creatine phosphokinase. CONCLUSION: In the subgroup analysis of a randomized clinical trial in Chinese OSA participants with EDS, solriamfetol was effective and well tolerated regardless of adherence to primary OSA therapy. No clinically meaningful impact of solriamfetol on the use of primary OSA therapy was found.

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BACKGROUND AND OBJECTIVES: Excessive daytime sleepiness (EDS) is a prominent symptom of obstructive sleep apnea (OSA), negatively affecting patients' quality of life. The objective of this study was to assess the efficacy and safety of solriamfetol in patients with OSA with EDS from China. METHODS: This multicenter, randomized, double-blind, placebo-controlled phase 3 trial compared solriamfetol (75/150 mg once daily) with placebo for 12 weeks. Adults diagnosed with OSA, mean Maintenance of Wakefulness Test (MWT) sleep latency < 30 min, and Epworth Sleepiness Scale (ESS) score ≥ 10 were included. Patients with disorders causing EDS other than OSA were excluded. Co-primary endpoints were change from baseline to week 12 in MWT mean sleep latency and ESS score; a key secondary endpoint was improvement on Patient Global Impression of Change (PGI-C), assessed on a seven-point scale. MWT was performed at baseline and at weeks 2, 5, and 12, whereas the ESS and PGI-C were evaluated at weeks 2, 5, 8, and 12. Safety and tolerability were assessed on the basis of treatment-emergent adverse events (TEAEs), laboratory tests, vital signs, 24-h ambulatory blood pressure monitoring, 12-lead electrocardiogram, and physical examination. Statistical analyses of co-primary endpoints were performed on the full analysis set (FAS) using a mixed model for repeated measures (MMRM). Safety analyses were performed on the safety population. A hierarchical testing sequence was used to control multiplicity. RESULTS: Of the 204 patients randomized (1:1) into placebo and solriamfetol groups, 192 completed the study (96 in each group). Co-primary endpoints were met, with significantly increased mean MWT sleep latency (P < 0.0001) and decreased ESS score (P = 0.0017) in the solriamfetol group (MWT, n = 95; ESS, n = 97) versus placebo (MWT, n = 95; ESS, n = 96) at week 12. Higher proportion of participants receiving solriamfetol (n = 90; 89.1%) reported improvement in PGI-C versus placebo (n = 77; 77.0%; P = 0.0221). At least one TEAE was reported in solriamfetol (n = 84; 82.4%) and placebo (n = 67; 65.7%) groups. The occurrence of serious TEAEs was low, with one incidence in both groups. Most frequently reported TEAEs in solriamfetol group included upper respiratory tract infection, dizziness, hyperuricemia, hypertension, hyperlipidemia, hypertriglyceridemia, and increased blood creatine phosphokinase. Most TEAEs were of mild/moderate severity and did not lead to study treatment discontinuation. CONCLUSIONS: Solriamfetol demonstrated substantial efficacy and acceptable safety in Chinese patients with OSA with EDS, reinforcing its role as a viable treatment option. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06103825.

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Introduction Wake-promoting agents (WPAs), such as solriamfetol, have emerged as effective treatment options for treating excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). However, the impact of solriamfetol on nocturnal sleep quality remains underexplored. This exploratory analysis of a 12-week, randomized, double-blind, placebo-controlled, multicenter, parallel-arm, phase 3 trial involving Chinese patients with OSA-EDS evaluated the effect of solriamfetol on nocturnal sleep quality. Methods Participants were randomized (1:1) to receive solriamfetol (150 mg) or placebo once daily. The coprimary efficacy endpoints were the changes from baseline to week 12 in mean sleep latency during the Maintenance Wakefulness Test and in Epworth Sleepiness Scale scores. The exploratory endpoints included changes in participants’ polysomnography (PSG) parameters from baseline at Weeks 2, 5, and 12. These parameters were unadjusted and hypothesis-generating. The sleep quality parameters included total sleep time (TST) and wakefulness after sleep onset (WASO). Respiratory parameters included mean oxygen saturation (SaO 2 ), minimum SaO 2 , apnea index, and apnea-hypopnea index (AHI). Results Of the 357 participants screened, 201 were included in the full analysis set (FAS) (solriamfetol, n = 101; placebo, n = 100). At all-time points (Weeks 2, 5, and 12), no significant changes in TST, WASO, stage N2 sleep, and AHI were observed between the solriamfetol and placebo groups ( P &amp;gt; 0.05). No significant changes were observed in N1 and N3, although significant changes were observed in N1 at Week 2 ( P = 0.0022) and N3 at Week 5 ( P = 0.0212). Conclusion No clinically significant or consistent changes in PSG parameters were observed compared with placebo, indicating that solriamfetol morning administration has no significant effect on nocturnal sleep parameters.

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