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

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).

A multicenter, 12-month, open-label, single-arm safety study of oxycodone-hydrochloride/naltrexone-hydrochloride extended-release capsules (ALO-02) in patients with moderate-to-severe chronic noncancer pain.

OBJECTIVE: To evaluate the long-term safety of oxycodone-hydrochloride and sequestered naltrexone-hydrochloride (ALO-02) administered for up to 12 months. DESIGN: Open-label, single-arm safety study. SETTING: Thirty-two US research centers (ClinicalTrials.gov identifier NCT01428583). PATIENTS: Three hundred ninety-five adults (opioid experienced and opioid naïve) with moderate-to-severe chronic noncancer pain (CNCP). INTERVENTIONS: Open-label, oral ALO-02 capsules, daily dose ranging from 20 to 160 mg oxycodone for up to 12 months. MAIN OUTCOME MEASURES: Number and type of adverse events (AEs) and drugrelated AEs, including assessments of withdrawal (Clinical Opiate Withdrawal Scale; COWS), pharmacokinetics, efficacy, and aberrant behaviors (Current Opioid Misuse Measure). RESULTS: A total of 193 (48.9 percent) patients received ALO-02 for ≥181 days and 105 (26.6 percent) patients for ≥361 days. The most common treatment-emergent AEs were nausea (25.3 percent), constipation (21.3 percent), vomiting (13.9 percent), and headache (11.6 percent). The most common drug-related AEs were constipation (18.0 percent), nausea (14.9 percent), somnolence (8.4 percent), fatigue (6.8 percent), dizziness (5.6 percent), and vomiting (5.1 percent). A majority of patients (86.6 percent) had a maximum COWS total score below the level for mild withdrawal symptoms at every visit throughout the study. Pain severity scores as measured by the short Form of the Brief Pain Inventory (BPI-SF) decreased over time. CONCLUSIONS: Repeat dosing of ALO-02 for up to 12 months is safe and well tolerated in a CNCP population of both opioid-experienced and opioid-naïve patients. ALO-02 demonstrated a safety profile consistent with extended-release opioids and the expected analgesic efficacy. The addition of sequestered naltrexone had no significant clinical effect on patients when taken as directed.

Randomized polysomnography study of gabapentin enacarbil in subjects with restless legs syndrome.

We assessed the efficacy and tolerability of gabapentin enacarbil in the treatment of moderate to severe primary restless legs syndrome and associated sleep disturbance. This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover polysomnography study of gabapentin enacarbil 1200 mg or placebo taken once daily. Subjects were randomized 1:1 to a sequence of gabapentin enacarbil:placebo or placebo:gabapentin enacarbil, receiving each treatment for 4 weeks. The primary end point was the mean change from baseline at weeks 4 and 10 (4/10) last observation carried forward in wake time during sleep. The key secondary end point was the mean change from baseline at weeks 4/10 last observation carried forward in periodic limb movements associated with arousal per hour of sleep. Tolerability assessments included adverse events. One hundred thirty-six subjects were randomized (gabapentin enacarbil:placebo, 67; placebo:gabapentin enacarbil, 69), and 114 (gabapentin enacarbil:placebo, 53; placebo:gabapentin enacarbil, 61) completed the study. Gabapentin enacarbil 1200 mg significantly reduced wake time during sleep (mean change from baseline [adjusted mean treatment difference]: -26.0 minutes; P < .0001) and periodic limb movements associated with arousal per hour of sleep (adjusted mean treatment difference: -3.1 periodic limb movements with arousal/hour; P = .002) compared with placebo at weeks 4/10 last observation carried forward. The most commonly reported adverse events were dizziness (gabapentin enacarbil 20%, placebo 2%) and somnolence (gabapentin enacarbil 13%, placebo 2%). Gabapentin enacarbil 1200 mg once daily significantly reduces restless legs syndrome-associated sleep disturbance and periodic limb movements associated with arousal per hour of sleep and is generally well tolerated in adults with moderate to severe primary restless legs syndrome.