Solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects, is currently being evaluated for the reduction of sleepiness and improvement of wakefulness in patients with narcolepsy and obstructive sleep apnea. The purpose of this study was to evaluate the effect of food on the pharmacokinetic (PK) parameters and bioavailability of solriamfetol at the highest intended therapeutic dose in healthy adults and to characterize its renal excretion under fasting conditions. In this open-label, randomized, crossover study, healthy adult subjects received a single 300-mg dose of solriamfetol in a fasted condition (10 h) and in a fed condition (30 min after the start of a standardized high-fat, high-calorie breakfast), with at least a 7-day washout period between doses. Blood samples for PK analyses were collected during both conditions at prespecified time points. Urine samples were collected up to 48 h postdose in the fasted condition. Samples were analyzed for solriamfetol (plasma and urine) and N-acetyl solriamfetol (urine) by using validated LC-MS/MS bioanalytical methods. The effect of food on solriamfetol relative bioavailability was examined by comparing the 90% confidence intervals (CIs) of the fed/fasted ratios of natural log-transformed PK parameters Cmax, AUC0-t, and AUC0-∞ with the prespecified range of 80%-125%. Safety and tolerability were also assessed. A total of 32 subjects were enrolled (50% female; 53.1% black, 46.9% white; mean age, 35.6 years), and 31 were included in the PK analyses. Solriamfetol was rapidly absorbed in both conditions. The 90% CIs for the fed/fasted geometric mean ratios were 89.2-98.8 for Cmax (ratio of 93.9%) and 93.8-101.5 for AUC0-∞ (ratio of 97.6%), indicating the absence of a food effect. In the fasted condition, 89.8% of solriamfetol was recovered in urine as unchanged drug over 48 h; 1.1% was excreted as a minor metabolite, N-acetyl solriamfetol. A total of 55 adverse events (AEs), all mild, were reported by 18 subjects (56.3%). The frequency and type of AEs were similar in the 2 conditions; the most common AEs (insomnia, headache, hypervigilance, decreased appetite, and nausea) were all mild in severity and resolved without treatment. Solriamfetol relative bioavailability was bioequivalent in the fed and fasted conditions, showing that solriamfetol can be taken without regard to meals; furthermore, tolerability was similar in both conditions. Renal excretion of unchanged drug is the primary route of elimination.