The novel dopamine and norepinephrine reuptake inhibitor (DNRI), JZP-110 (Jazz) demonstrated efficacy in its Phase 3 studies (TONES 3 and TONES 4) evaluating adults with excessive sleepiness associated with obstructive sleep apnea (OSA).
The 12-week, 5-arm, parallel-group, double-blind, placebo-controlled, randomized TONES 3 (n=476) study evaluated patients with excessive sleepiness in OSA. They were randomized to JZP-110 37.5mg (n=59), 75mg (n=61), 150mg (n=118), 300mg (n=119), or placebo (n=119).
The primary endpoints were the change in mean sleep latency on the Maintenance of Wakefulness Test (MWT) and in the Epworth Sleepiness Scale (ESS) score from baseline to Week 12.
All JZP-110 doses were associated with statistically significant improvements in both MWT and in the ESS. Treatment with JZP-110 led to greater mean MWT sleep latency by >10 minutes at all time points for the 150mg (11.0 minutes; P<0.0001) and 300mg (13.0 minutes; P<0.0001) doses. Moreover at Week 12, JZP-110 lowered mean ESS scores by >7 points for the 150mg (-7.7; P<0.0001) and 300mg (-7.9; P<0.0001) doses.
Significant overall improvements were also noted on the key secondary endpoint of improved Patient Global Impression of Change (PGIc) scale, with 90% of patients in the 150mg and 300mg arms reporting overall improvement at Week 12.
TONES 4 (n=174) was a 6-week study consisting of 2-week flexible-dose titration phase followed by 2-weeks of stable dose treatment. The main analysis looked at the difference between JZP-110 vs. placebo on the changes in MWT and ESS. Treatment with JZP-110 led to a mean sleep latency on MWT of -1.0 minute (P<0.0001) vs. -12.1 minutes for placebo by the end of the withdrawal phase at Week 6. Also, there was a -0.1 change (P<0.0001) in the ESS scale with JZP-110 vs. +4.5 with placebo.
JZP-110, a selective DNRI, is being investigated for the treatment of excessive sleepiness in adults with narcolepsy, OSA, and Parkinson’s disease. Its clinical program includes more than 2,000 participants across 20 studies.
For more information visit JazzPharma.com.