SAN DIEGO – The selective dopamine and norepinephrine reuptake inhibitor solriamfetol is effective in reducing sleepiness in patients with narcolepsy, according to results of a phase 3 study.
At 150-mg and 300-mg doses, the drug had statistically significant effects on objective and subjective measures.
There are wake-promoting drugs available, such as amphetamine-related drugs that are often used off label, but addiction liability is a concern. The nonamphetamine modafinil has been approved by the Food and Drug Administration since 1998.
Jazz Pharmaceuticals is in the process of submitting solriamfetol for FDA evaluation. If approved, the drug will add to the options available for narcolepsy patients. “All of the available drugs have some limitations. Some have more abuse liability than others. Some have more robust wake-promoting properties than others. We haven’t done any head-to-head comparisons, so I can’t tell you how we will stack up,” Philip Jochelson, MD, said in an interview. Dr. Jochelson is vice president of clinical development at Jazz Pharmaceuticals and presented the results of the study at a poster session at the annual meeting of the American Neurological Association.
An earlier study showed the drug had less abuse potential than the schedule IV stimulant phentermine. That’s not surprising given the drug’s mechanism of action, Dr. Jochelson said. Amphetamine-based drugs stimulate dopamine release, which can prompt a dopamine surge that people equate with a high, he said. Solriamfetol also affects dopamine, but it is a reuptake inhibitor, so it doesn’t produce a surge.
If the drug gains approval, it remains to be seen how it will be classified on the Drug Enforcement Agency Controlled Substance scale. “Where it will fall in that spectrum is speculative at this point,” said Dr. Jochelson.
In the current study, 236 adults (aged 18-75 years) with type 1 narcolepsy were randomized to once-daily placebo, 75 mg solriamfetol, 150 mg solriamfetol, or 300 mg solriamfetol; 27.1% of patients in the 300-mg group discontinued, compared with 7.3% in the 150-mg group, 16.9% in the 75-mg group, and 10.3% in the placebo group. The mean change from baseline on the Maintenance of Wakefulness Test was statistically significant in the 300-mg group (12.3 minutes vs. 2.1 minutes for placebo, P less than .0001) and the 150-mg group (9.8 minutes vs. 2.1 minutes, P less than .0001) but not the 75-mg group (4.7 minutes vs. 2.1 minutes).
The drug also outperformed placebo at week 12 on the Epworth Sleepiness Scale. The mean change in the 300-mg group was –6.4 vs. –1.6 for placebo (P less than .001), –5.4 in the 150-mg group (P less than .0001), and –3.8 in the 75-mg group (P less than .05).
By both Maintenance of Wakefulness Test and Epworth Sleepiness Scale measures, the 150-mg and 300-mg solriamfetol groups had statistically significant differences as early as week 1.
The drug had some adverse effects, which were expected based on its pharmacologic profile. These included increases in headache (5.1% with placebo, 10.2% with 75 mg, 23.7% with 150 mg, 30.5% with 300 mg), nausea (1.7% for placebo, 5.1% for 75 mg, 10.2% for 150 mg, 16.9% for 300 mg), anxiety (1.7% with placebo, 1.7% with 75 mg, 5.1% with 150 mg, 8.5% with 300 mg), and insomnia (0% for placebo, 3.4% for 75 mg, 0% for 150 mg, 5.1% for 300 mg). Other adverse events occurring in at least 5% of patients were decreased appetite, nasopharyngitis, and dry mouth.
The study was funded by Jazz Pharmaceuticals. Dr. Jochelson is an employee of Jazz.