Effects of Solriamfetol on Quality-of-Life Measures from a 12-Week Phase 3 Randomized Controlled Trial

Terri E Weaver, Christopher L Drake, Heike Benes, Thomas Stern, James Maynard, Stephen G Thein, James M Andry Sr, John D Hudson, Dan Chen, Lawrence P Carter, Morgan Bron, Lawrence Lee, Jed Black, Richard K Bogan, Terri E Weaver, Christopher L Drake, Heike Benes, Thomas Stern, James Maynard, Stephen G Thein, James M Andry Sr, John D Hudson, Dan Chen, Lawrence P Carter, Morgan Bron, Lawrence Lee, Jed Black, Richard K Bogan

Abstract

Rationale: Excessive daytime sleepiness in patients with obstructive sleep apnea is associated with substantial burden of illness.Objectives: To assess treatment effects of solriamfetol, a dopamine/norepinephrine reuptake inhibitor, on daily functioning, health-related quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness as additional outcomes in a 12-week phase 3 trial (www.clinicaltrials.gov identifier NCT02348606).Methods: Participants (N = 476) were randomized to solriamfetol 37.5, 75, 150, or 300 mg or to placebo. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-item Short Form Health Survey version 2. A mixed-effects model with repeated measures was used for comparisons with placebo.Results: Demographics, baseline disease characteristics, daily functioning, health-related quality of life, and work productivity were similar across groups. At Week 12, increased functioning and decreased impairment were observed with solriamfetol 150 and 300 mg (mean difference from placebo [95% confidence interval]) on the basis of Functional Outcomes of Sleep Questionnaire total score (1.22 [0.57 to 1.88] and 1.47 [0.80 to 2.13], respectively), overall work impairment (-11.67 [-19.66 to -3.69] and -11.75 [-19.93 to -3.57], respectively), activity impairment (-10.42 [-16.37 to -4.47] and -10.51 [-16.59 to -4.43], respectively), physical component summary (2.07 [0.42 to 3.72] and 1.91 [0.22 to 3.59], respectively), and mental component summary (150 mg only, 2.05 [0.14 to 3.96]). Common adverse events were headache, nausea, decreased appetite, and anxiety.Conclusions: Solriamfetol improved measures of functioning, quality of life, and work productivity in participants with obstructive sleep apnea and excessive daytime sleepiness. Safety was consistent with previous studies.Clinical trial registered with www.clinicaltrials.gov (NCT02348606).

Keywords: JZP-110; Sunosi; excessive daytime sleepiness; health-related quality of life; obstructive sleep apnea.

Figures

Figure 1.
Figure 1.
Study design for the phase 3, 12-week, double-blind, randomized, placebo-controlled, parallel-group study. Note: Numbers indicate safety population.
Figure 2.
Figure 2.
Participant disposition. AE = adverse event; ESS = Epworth Sleepiness Scale; mITT = modified intention to treat; MWT = Maintenance of Wakefulness Test. Adapted from Reference .
Figure 3.
Figure 3.
Change in FOSQ-10 total scores from baseline to Week 12 (mITT population). *P < 0.05 and †P < 0.0001 versus placebo. P values are uncontrolled for multiplicity; hence, they are nominal. Positive response from baseline denotes improvement. FOSQ-10 = Functional Outcomes of Sleep Questionnaire short version (10-item); LS = least squares; mITT = modified intention to treat; SE = standard error.
Figure 4.
Figure 4.
Change in WPAI:SHP from baseline to Week 12 (mITT population). P values are uncontrolled for multiplicity; hence, they are nominal. *P < 0.05 versus placebo. †P < 0.001 versus placebo. Values are for the mITT population (n = 459): percentage of work time missed due to OSA (absenteeism), percentage impairment while working due to OSA (presenteeism), percentage of overall work impairment due to OSA (absenteeism + presenteeism), and percentage activity impairment due to OSA. Negative response from baseline denotes improvement. LS = least squares; mITT = modified intention to treat; OSA = obstructive sleep apnea; SE = standard error; WPAI:SHP = Work Productivity and Activity Impairment Questionnaire: Specific Health Problem.
Figure 5.
Figure 5.
Change in the SF-36v2 (A) PCS and MCS and (B) subscale scores from baseline to Week 12 (mITT population). P values are uncontrolled for multiplicity; hence, they are nominal. *P < 0.05 versus placebo. †P < 0.001 versus placebo. Positive response from baseline denotes improvement. Values are for the mITT population (n = 459). LS = least squares; MCS = mental component summary; mITT = modified intention to treat; PCS = physical component summary; SE = standard error; SF-36v2 = 36-item Short Form Health Survey version 2.
Figure 6.
Figure 6.
Change in EQ VAS from baseline to Week 12 (mITT population). Positive response denotes improvement from baseline. EQ VAS = EuroQol visual analogue scale; LS = least squares; mITT = modified intention to treat; SD = standard deviation; SE = standard error.

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Source: PubMed

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