Novel Sublingual Low-Dose Zolpidem Tablet Reduces Latency to Sleep Onset following Spontaneous Middle-of-the-Night Awakening in Insomnia in a Randomized, Double-Blind, Placebo-Controlled, Outpatient Study

Thomas Roth, PhD1, Andrew Krystal, MD2; Frank J. Steinberg, DO3; Nikhilesh N. Singh, PhD4; Margret Moline, PhD5

1Henry Ford Hospital, Detroit, MI; 2Duke University Medical Center, Durham, NC; 3Chief Medical Consultant, Transcept Pharmaceuticals, Inc., Point Richmond, CA; 4Transcept Pharmaceuticals, Inc., Point Richmond, CA;  5Purdue pharma L P Stamford, CT

Study Objectives: To evaluate efficacy and safety of 3.5-mg zolpidem tartrate sublingual tablets (ZST) on latency to sleep onset after middle-of-the night (MOTN) awakenings in patients with insomnia characterized by difficulty returning to sleep after MOTN awakenings.

Design: Multicenter randomized, double-blind, placebo-controlled, parallel-group.

Setting: Outpatient.

Patients: There were 295 adults (median age 43 y; 68, 1% female) with primary insomnia and difficulty returning to sleep after MOTN awakenings (three or more MOTH awakenings/wk during screening).

Interventions: After a 2-wk, single-blind placebo eligibility period, participants were randomized 1:1 to as needed MOTH dosing with 3.5 mg ZST or placebo for 28 nights. An interactive voice response system determined if the study drug could be taken and recorded sleep/wake efficacy measures.

Results: ZST significantly (P < 0.0001) decreased latency to sleep onset over 4 wk (baseline 68.1 min; ZST 38.2 min) compared with placebo (baseline 69.4 min; placebo 56.4 min). Ratings of morning sleepiness/alertness significantly (p = 0.0041) favored the ZST group on nights medica-tion was taken but not on other nights. Participants in the ZST group took the study drug on 62% of nights during the 4 wk; members of the placebo group took study medication on 64% of nights. Adverse events were generally mild at the same rate (19.3% of participants) in both groups. There were no treatment-related serious adverse events (SAEs), and one adverse event-related study discontinuation from the placebo group. Dosing/week did not increase across the study.

Conclusion: 3.5 mg ZST used as needed significantly reduced latency to return to sleep in comparison with placebo in these patients with insomnia. Sleep quality was improved, and morning sleepiness/alertness scores also improved. ZST was well tolerated. These data demonstrate the utility of a sleep-promoting agent when used as needed in the MOTN.

Clinical Trial Information: Clinical Trials Registration: NCT00466193: “A Study of Zolpidem Tartrate Tablet in Adult Patients with Insomnia”

Keywords: Insomnia, middle-of-the-night awakenings, MOTN insomnia, pharmacotherapy, zolpidem

Citation: Roth T; Krystal A; Steinberg FJ; Sing NN; Moline M. Novel sublingual low-dose zolpidem tablet reduces latency to sleep onset fol-lowing spontaneous middle-of-the-night awakening in insomnia in a randomized, double-blind, placebo-controlled, outpatient study. SLEEP 2013;36(2):189-196