A Phase 2 Randomized Dose-Finding Study With Esmirtazapine in Patients With Primary Insomnia

Area of Science:

• Pharmacology
• Sleep Medicine
• Clinical Trials

Background:

• Mirtazapine, an antidepressant, shows potential as an alternative to traditional hypnotics.
• Primary insomnia affects a significant portion of the adult population, impacting overall health and well-being.

Purpose of the Study:

• To evaluate the efficacy and safety of esmirtazapine (S-mirtazapine maleic acid salt) in treating primary insomnia.
• To determine optimal dosing for esmirtazapine in improving sleep parameters.

Main Methods:

• A balanced 4-way crossover study involving 18-65 year old patients with primary insomnia.
• Polysomnography and patient-reported outcomes were used over 2 sleep laboratory nights, separated by 5-day placebo washout periods.
• Doses tested: placebo, 1.5 mg, 3.0 mg, and 4.5 mg of esmirtazapine.

Main Results:

• All esmirtazapine doses significantly increased total sleep time by at least 25 minutes compared to placebo (P ≤ 0.001).
• Reduced wake time after sleep onset and improved latency to persistent sleep were observed with 3.0 and 4.5 mg doses (P ≤ 0.0001 and P ≤ 0.01, respectively).
• Patient-reported sleep quality improved with 3.0 and 4.5 mg doses; calmness increased with 4.5 mg.

Conclusions:

• Esmirtazapine, at doses from 1.5 to 4.5 mg/day, effectively improves both the quantity and quality of sleep in primary insomnia patients.
• The drug was generally well-tolerated, with no serious adverse events or significant safety concerns identified.
• No consistent residual effects on morning alertness or daytime functioning were noted, suggesting a favorable safety profile.