Investigational Drug Improves Maintenance of Wakefulness

DENVER—An investigational drug known as JZP-110 significantly improves the ability to stay awake, compared with placebo, in patients with narcolepsy, according to data presented at the 30th Anniversary Meeting of the Associated Professional Sleep Societies. The large effect sizes associated with the drug confirm the robustness of the results, according to the researchers.

JZP-110 is a selective dopamine and norepinephrine reuptake inhibitor in development as a treatment for excessive sleepiness and impaired wakefulness associated with narcolepsy and obstructive sleep apnea. In phase II trials, the drug improved wakefulness, compared with placebo, on the 40-minute Maintenance of Wakefulness Test (MWT). Studies of other agents, however, have reported sleep latency results using a 20-minute MWT.

Chad Ruoff, MD, Clinical Assistant Professor of Psychiatry and Behavioral Sciences at the Stanford Center for Sleep Sciences and Medicine in California, and colleagues conducted a post hoc analysis of data from two phase II trials to evaluate changes from baseline in mean MWT sleep latency associated with JZP-110, censoring data to include only the first 20 minutes of the 40-minute MWT. In one study, 33 adults with narcolepsy (with or without cataplexy) were randomized to receive two weeks of treatment with placebo or JZP-110. Active treatment was administered at a dose of 150 mg/day during the first week and at a dose of 300 mg/day during the second week. In the second study, 93 adults with narcolepsy (with or without cataplexy) were randomized to receive placebo or JZP-110 for 12 weeks. The dose of drug was 150 mg/day during the first four weeks and 300 mg/day for the remaining eight weeks.

For both studies, researchers performed 40-minute trials of the MWT (four trials in the first study and five trials in the second study). The primary efficacy end point for both studies was the change from baseline at end of treatment in sleep latency, as measured by the MWT. For the current analysis, the researchers censored the data at 20 minutes and calculated effect sizes.

Regardless of whether the data were censored at 20 minutes or at 40 minutes, JZP-110 resulted in a statistically significant increase from baseline in MWT sleep latency, compared with placebo, in both studies. In the first study, mean changes in sleep latency were 12.7 minutes with the drug versus 0.9 minutes with placebo when censored at 40 minutes. The changes were 8.9 minutes with drug and 0.4 minutes with placebo when data were censored at 20 minutes. In the second study, mean changes in MWT were 12.8 minutes with JZP-110 and 2.1 minutes with placebo when data were censored at 40 minutes. Mean changes were 8.9 minutes for drug and 1.1 minutes for placebo when data were censored at 20 minutes.

Effect sizes were large and slightly greater for 20-minute censored data (1.54 in the first study and 1.41 in the second study) than for 40-minute censored data (1.37 in the first study and 1.17 in the second study). Researchers observed two serious adverse events--one case of conversion disorder and one case of acute cholecystitis--that they considered unrelated to the study drug. Few discontinuations resulted from adverse events.

—Erik Greb

DENVER—An investigational drug known as JZP-110 significantly improves the ability to stay awake, compared with placebo, in patients with narcolepsy, according to data presented at the 30th Anniversary Meeting of the Associated Professional Sleep Societies. The large effect sizes associated with the drug confirm the robustness of the results, according to the researchers.

JZP-110 is a selective dopamine and norepinephrine reuptake inhibitor in development as a treatment for excessive sleepiness and impaired wakefulness associated with narcolepsy and obstructive sleep apnea. In phase II trials, the drug improved wakefulness, compared with placebo, on the 40-minute Maintenance of Wakefulness Test (MWT). Studies of other agents, however, have reported sleep latency results using a 20-minute MWT.

Chad Ruoff, MD, Clinical Assistant Professor of Psychiatry and Behavioral Sciences at the Stanford Center for Sleep Sciences and Medicine in California, and colleagues conducted a post hoc analysis of data from two phase II trials to evaluate changes from baseline in mean MWT sleep latency associated with JZP-110, censoring data to include only the first 20 minutes of the 40-minute MWT. In one study, 33 adults with narcolepsy (with or without cataplexy) were randomized to receive two weeks of treatment with placebo or JZP-110. Active treatment was administered at a dose of 150 mg/day during the first week and at a dose of 300 mg/day during the second week. In the second study, 93 adults with narcolepsy (with or without cataplexy) were randomized to receive placebo or JZP-110 for 12 weeks. The dose of drug was 150 mg/day during the first four weeks and 300 mg/day for the remaining eight weeks.

For both studies, researchers performed 40-minute trials of the MWT (four trials in the first study and five trials in the second study). The primary efficacy end point for both studies was the change from baseline at end of treatment in sleep latency, as measured by the MWT. For the current analysis, the researchers censored the data at 20 minutes and calculated effect sizes.

Regardless of whether the data were censored at 20 minutes or at 40 minutes, JZP-110 resulted in a statistically significant increase from baseline in MWT sleep latency, compared with placebo, in both studies. In the first study, mean changes in sleep latency were 12.7 minutes with the drug versus 0.9 minutes with placebo when censored at 40 minutes. The changes were 8.9 minutes with drug and 0.4 minutes with placebo when data were censored at 20 minutes. In the second study, mean changes in MWT were 12.8 minutes with JZP-110 and 2.1 minutes with placebo when data were censored at 40 minutes. Mean changes were 8.9 minutes for drug and 1.1 minutes for placebo when data were censored at 20 minutes.

Effect sizes were large and slightly greater for 20-minute censored data (1.54 in the first study and 1.41 in the second study) than for 40-minute censored data (1.37 in the first study and 1.17 in the second study). Researchers observed two serious adverse events--one case of conversion disorder and one case of acute cholecystitis--that they considered unrelated to the study drug. Few discontinuations resulted from adverse events.

—Erik Greb

DENVER—An investigational drug known as JZP-110 significantly improves the ability to stay awake, compared with placebo, in patients with narcolepsy, according to data presented at the 30th Anniversary Meeting of the Associated Professional Sleep Societies. The large effect sizes associated with the drug confirm the robustness of the results, according to the researchers.

JZP-110 is a selective dopamine and norepinephrine reuptake inhibitor in development as a treatment for excessive sleepiness and impaired wakefulness associated with narcolepsy and obstructive sleep apnea. In phase II trials, the drug improved wakefulness, compared with placebo, on the 40-minute Maintenance of Wakefulness Test (MWT). Studies of other agents, however, have reported sleep latency results using a 20-minute MWT.

Chad Ruoff, MD, Clinical Assistant Professor of Psychiatry and Behavioral Sciences at the Stanford Center for Sleep Sciences and Medicine in California, and colleagues conducted a post hoc analysis of data from two phase II trials to evaluate changes from baseline in mean MWT sleep latency associated with JZP-110, censoring data to include only the first 20 minutes of the 40-minute MWT. In one study, 33 adults with narcolepsy (with or without cataplexy) were randomized to receive two weeks of treatment with placebo or JZP-110. Active treatment was administered at a dose of 150 mg/day during the first week and at a dose of 300 mg/day during the second week. In the second study, 93 adults with narcolepsy (with or without cataplexy) were randomized to receive placebo or JZP-110 for 12 weeks. The dose of drug was 150 mg/day during the first four weeks and 300 mg/day for the remaining eight weeks.

For both studies, researchers performed 40-minute trials of the MWT (four trials in the first study and five trials in the second study). The primary efficacy end point for both studies was the change from baseline at end of treatment in sleep latency, as measured by the MWT. For the current analysis, the researchers censored the data at 20 minutes and calculated effect sizes.

Regardless of whether the data were censored at 20 minutes or at 40 minutes, JZP-110 resulted in a statistically significant increase from baseline in MWT sleep latency, compared with placebo, in both studies. In the first study, mean changes in sleep latency were 12.7 minutes with the drug versus 0.9 minutes with placebo when censored at 40 minutes. The changes were 8.9 minutes with drug and 0.4 minutes with placebo when data were censored at 20 minutes. In the second study, mean changes in MWT were 12.8 minutes with JZP-110 and 2.1 minutes with placebo when data were censored at 40 minutes. Mean changes were 8.9 minutes for drug and 1.1 minutes for placebo when data were censored at 20 minutes.

Effect sizes were large and slightly greater for 20-minute censored data (1.54 in the first study and 1.41 in the second study) than for 40-minute censored data (1.37 in the first study and 1.17 in the second study). Researchers observed two serious adverse events--one case of conversion disorder and one case of acute cholecystitis--that they considered unrelated to the study drug. Few discontinuations resulted from adverse events.

—Erik Greb