Long-term efficacy and safety of zolpidem extended-release 12.5 mg, administered 3 to 7 nights per week for 24 weeks, in patients with chronic primary insomnia: a 6-month, randomized, double-blind, placebo-controlled, parallel-group, multicenter study.

Abstract

STUDY OBJECTIVES:

To evaluate long-term efficacy and safety of zolpidem extended-release 3 to 7 nights/week for chronic primary insomnia.

DESIGN:

Multicenter, 25-week, phase IIIb, randomized, double-blind, placebo-controlled, parallel-group.

SETTING:

Outpatient; visits every 4 weeks.

PATIENTS:

Aged 18 to 64 years; DSM-IV criteria for chronic primary insomnia; > or =3 months of difficulty initiating or maintaining sleep or experiencing nonrestorative sleep.

INTERVENTIONS:

Single-dose zolpidem extended-release 12.5 mg (n = 669) or placebo (n = 349), self-administered from a minimum of 3 nights/week to a maximum of 7 nights/week.

MEASUREMENTS AND RESULTS:

Patient's Global Impression (PGI) and Clinical Global Impression-Improvement (CGI-I) were assessed every 4 weeks up to week 24. Patient Morning Questionnaire (PMQ), recorded daily, assessed subjective sleep measures-sleep onset latency (SOL), total sleep time (TST), number of awakenings (NAW), wake time after sleep onset (WASO), and quality of sleep (QOS)-and next-day functioning. At week 12, PGI, Item 1 (aid to sleep), the primary endpoint, was scored as favorable (i.e., "helped me sleep") by 89.8% of zolpidem patients vs. 51.4% of placebo patients (P < 0.0001, based on rank score) and at week 24 by 92.3% of zolpidem extended-release patients vs. 59.7% of placebo patients. Zolpidem extended-release also was statistically significantly superior to placebo at every time point for PGI (Items 1-4) and CGI-I (P < 0.0001, rank score), TST, WASO, QOS (P < 0.0001), and SOL (P < or = 0.0014); NAW (Months 2-6; P < 0.0001). Sustained improvement (P < 0.0001, all time points) was observed in morning sleepiness and ability to concentrate (P = 0.0014, month 6) with zolpidem extended-release compared with placebo. Most frequent adverse events for zolpidem extended-release were headache, anxiety and somnolence. No rebound effect was observed during the first 3 nights of discontinuation.

CONCLUSIONS:

These findings establish the efficacy of 3 to 7 nights per week dosing of zolpidem extended-release 12.5 mg for up to 6 months. Treatment provided sustained and significant improvements in sleep onset and maintenance and also improved next-day concentration and morning sleepiness.

• Authors: Andrew D Krystal, Milton Erman, Gary K Zammit, C Soubrane, Thomas Roth, ZOLONG Study Group
• Journal: Sleep (Sleep) Vol. 31 Issue 1 Pg. 79-90 (Jan 2008) ISSN: 0161-8105 [Print] United States
• PMID: 18220081 (Publication Type: Controlled Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Delayed-Action Preparations
• Hypnotics and Sedatives
• Pyridines
• Zolpidem

Topics

• Adult
• Analysis of Variance
• Chronic Disease
• Delayed-Action Preparations
• Double-Blind Method
• Drug Administration Schedule
• Drug Tolerance
• Female
• Humans
• Hypnotics and Sedatives (administration & dosage, adverse effects)
• Male
• Middle Aged
• Pyridines (administration & dosage, adverse effects)
• Severity of Illness Index
• Sleep Initiation and Maintenance Disorders (drug therapy)
• Surveys and Questionnaires
• Zolpidem