LOS ANGELES — People with type 1 and type 2 narcolepsy maintained wakefulness and experienced less excessive sleepiness when treated with a new inhibitor in a 12-week, randomized, placebo-controlled phase 3 study.
“Solriamfetol is a novel alerting medication that has been shown, both subjectively and objectively, to have a major effect on improving alertness in patients with narcolepsy,” Michael Thorpy, MB, ChB, professor of neurology at the Albert Einstein College of Medicine and director of the Sleep-Wake Disorder Center at Montefiore Medical Center, Bronx, New York, told Medscape Medical News.
“Many patients develop narcolepsy at an early age. The median age of onset is 16 years…but median age at diagnosis is closer to 30 years, so, many patients have a great deal of disability for many years of their life before the narcolepsy is recognized and they can start appropriate treatment.” He added, “Despite receiving appropriate treatment, many patients continue to be disabled,” and new therapies are needed.
The study was presented here at a plenary presentation at the American Academy of Neurology (AAN) 2018 Annual Meeting.
Study Details
Solriamfetol is a selective, low-potency, dopamine-norepinephrine reuptake inhibitor. Previous researchers originally assessed the inhibitor as a treatment for major depressive disorder, “and they noticed it had significant wake-promoting activities,” he said.
Thorpy and his colleagues randomly assigned 239 adults with narcolepsy to placebo or a 75-mg, 150-mg or 300-mg solriamfetol dose group. At baseline, participants had a mean sleep latency of less than 25 minutes on the Maintenance of Wakefulness Test (MWT) and an Epworth Sleepiness Scale (ESS) score of 10 or greater. They also had to have adequate sleep, with a minimum nightly sleep time of 6 hours or more.
This study was designated a 2018 AAN Abstract of Distinction.
“Patients were rated by clinicians as moderately to severely ill in most cases,” Thorpy said. “These were patients who were severely affected by narcolepsy.”
There were 52 patients in the placebo group, 49 in the 75-mg group, 51 in the 150-mg group, and 43 in the 300-mg dose group at 12 weeks after some dropouts. The intent-to-treat analysis included 231 patients. The mean baseline ESS score was 17.2 and the mean baseline MWT mean sleep latency time was 7.5 minutes.
Change from baseline to week 12 in subjective MWT mean sleep latency was one of the primary study endpoints. The two highest doses produced statistically significant improvements on the MWT at 12 weeks compared with placebo (P < .001). “There was also improvement at the first week, and the changes found were consistent throughout the duration of the study,” he said.
The 75-mg dose was associated with statistically significant improvements at the first week but not at week 12. The least-squares mean changes from baseline to week 12 were 12.3 minutes for 300 mg, 9.8 minutes for 150 mg, 4.7 minutes for 75 mg, and 2.1 minutes for the placebo groups.
The investigators also measured changes on the objective ESS from baseline, a second primary outcome.
“All three doses of solriamfetol produced statistically significant improvements in the ESS, so these patients were much less sleepy,” he said. “With the two highest does, this effect was seen in the first week and again throughout the duration of the study.”
The investigators reported mean decreases from baseline on the ESS of 6.4 for the 300-mg group, 5.4 for the 150-mg group, 3.8 for the 75-mg group, and 1.6 for the placebo group.
Change in patient global impression scores was a secondary study outcome. “All three solriamfetol dose groups had patients who improved in their overall clinical condition by the end of 12-week study.”
Type 1 narcolepsy is defined as presence of cataplexy and/or reduced hypocretin in the cerebral spinal fluid. Patients with type 2 narcolepsy do not have cataplexy but show relevant findings on polysomnography.
Cataplexy was present in about 30% of participants. Mean age in the study ranged from 34 to 38 years across the four groups. Women made up 58% to 71% of the cohorts, “which is fairly typical in studies of narcolepsy, even though the incidence is the same for males and females.”
Safety Data
Few adverse events occurred, Thorpy said. The most common were headache, nausea, and decreased appetite. One serious adverse event occurred in a patient in the 150-mg solriamfetol group; he experienced noncardiac chest pain and anxiety, which the investigator deemed was unrelated to the study medication. “This patient continued the study without any further occurrence.”
“In patients with type 1 or type 2 narcolepsy, solriamfetol at 150 and 300 mg resulted in statistically significant and robust effects at week 12 on the patient’s ability to remain awake…and to [experience] reduced excessive daytime sleepiness,” he said. Significant effects in the 75-mg group were limited to the ESS results.
A meeting attendee asked about use of solriamfetol to treat sleepiness in other disorders. “The wake-promoting effect seems to be fairly nonspecific, so it’s probably going to improve sleepiness for a whole variety of neurologic disorders,” he replied. Studies examining solriamfetol for residual sleepiness associated with obstructive sleep apnea syndrome were recently completed, but research in other disorders have not been initiated to his knowledge, he added.
“Certainly, excessive daytime sleepiness is found in other neurologic disease aside from primarily narcolepsy,” Holly E. Hinson, MD, MCR, assistant professor of neurology and emergency medicine at Oregon Health & Science University in Portland, said when asked by Medscape Medical News to comment.
“It will be interesting to see if solriamfetol might be able to be applied in other conditions, like Parkinson’s disease, that exhibit excessive daytime sleepiness.” She added, “Hopefully this [study] will provide some momentum to investigate it in other diseases.”
Jazz Pharmaceuticals supported the study. T horpy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Jazz Pharmaceuticals, Merck & Co, and Teva Pharmaceutical Industries Ltd. Dr Hinson has disclosed no relevant financial relationship.
American Academy of Neurology (AAN) 2018 Annual Meeting. Clinical Trials Plenary Session. Abstract 003. Presented April 24, 2018.
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