MINNEAPOLIS--()--Results of a Phase 2 study sponsored by Somnus Therapeutics, Inc., add further evidence supporting the efficacy and safety of a novel bedtime therapeutic that addresses a major underserved need of insomnia patients: maintaining sleep. SKP-1041, a modified-release formulation of zaleplon, is designed to accomplish this by reducing middle-of-the-night (MOTN) awakenings without interfering with natural sleep onset and early deep sleep. At all three doses tested, SKP-1041 significantly reduced time spent awake during the night compared to placebo, with no evidence of next-morning adverse cognitive effects.
“The SKP-1041 formulation is engineered to deliver a short-acting agent, zaleplon, only during the time needed to maintain sleep. All of our clinical studies have confirmed that the formulation works as designed”
“In this study, we saw statistically significant reductions in the time spent awake during the night (WASO) for all three dosage strengths tested. For the 15 and 20 mg doses, there was a significant reduction in the number of middle-of-the-night awakenings during hours 3-7 of the 8-hour sleep period (NAASO3-7) as well as increased total sleep time for hours 3-7 (TST 3-7),” said study investigator Russell Rosenberg, Ph.D., CEO NeuroTrials Research, and the Atlanta School of Sleep Medicine. “Blood levels of zaleplon were measured over 8 hours and confirmed the release of active drug starting 2 hours after ingestion. This facilitates peak hypnotic efficacy during the hours when unwanted awakenings are most likely to occur. (see Figure 1) Using the Digit Symbol Substitution Test (DSST) and Digit Span Test (DST) to test for next-day effects on cognition, we saw no impairment compared to placebo at all three doses.”
“The SKP-1041 formulation is engineered to deliver a short-acting agent, zaleplon, only during the time needed to maintain sleep. All of our clinical studies have confirmed that the formulation works as designed,” said Gary Cupit, PharmD, Chief Executive Officer of Somnus Therapeutics. “We have seen consistent and reliable pharmacokinetics throughout our 3 Phase 1 studies and in the PK investigations of Phase 2. Furthermore, the formulation is well-tolerated. Adverse events in (the) more than 130 subjects included in our Phase 1 and 2 studies have been reported to be not significantly different from placebo. This is in addition to many years of safety data accumulated on immediate release zaleplon in clinical trials and over more than a decade on the market.”
About the study design and cognitive tests
The study (SOM201), conducted in 67 non-elderly (ages 24-64) adults with primary insomnia characterized by MOTN awakening, was a 4-way, double-blind, placebo-controlled, double-dummy crossover evaluation of SKP-1041, a modified-release formulation of zaleplon (more below). Conducted in a sleep laboratory setting, subjects were randomly assigned to receive SKP-1041 at 10, 15 or 20 mg doses taken immediately before bedtime. Sleep-wake episodes were recorded by polysomnography for 8 hours after lights-out. Residual cognitive effects were measured within 1 hour of awakening using DSST and DST.
These tests are frequently-employed methods to evaluate cognition and next-day residual effects of sedative drugs. The DSST evaluates high-level processes of attention, memory and executive functioning (frontal functions). The DST assesses short-term memory and working memory.
About MOTN Awakening
In the US general population, insomnia prevalence is estimated at about 30%, with about 15% suffering adverse daytime consequences. A widely-cited study found that one third of the American general population wake up during night at least three nights per week. Data from this and other studies show a significant association between insomnia and comorbidities, especially gastroesophageal reflux disease, mood disorders, and chronic pain. ("Nocturnal awakenings and comorbid disorders in the American general population" - Journal of Psychiatric Research, Maurice M. Ohayon, MD, DSc, PhD" 2008-05-06)
Zaleplon is a non-benzodiazepine GABA agent with a short half-life (~1 hour), and little or no residual hypnotic effect upon awakening. It has been marketed since 2000 in Sonata®, as 5, 10, and 20 mg immediate-release capsules for the treatment of sleep-onset insomnia, and since 2008 as various generic formulations. With a pharmacokinetic profile characterized by rapid absorption and elimination, zaleplon effectively induces sleep without unwanted residual effects, but because of its short half-life, is not routinely used to treat sleep maintenance.
SKP-1041 uses SkyePharma’s Geoclock™ technology to delay and sustain the release of zaleplon after bedtime administration. This delivery approach is designed to treat people who have difficulty maintaining sleep after falling asleep naturally, both allowing natural sleep induction and preventing middle-of-the-night awakening without residual effects. In June 2007, Somnus entered into an exclusive license with SkyePharma for the worldwide development and commercialization of SKP-1041. Under the agreement, SkyePharma will formulate and manufacture the product and Somnus will seek a partner to develop and commercialize it.
About the Geoclock™ controlled-release technology
The proprietary Geoclock™ (SkyePharma PLC, LSE: SKP) delivery system is a unique technology that allows delivery of a drug over a preset time period in a chronotherapy-focused press-coated tablet, with active drug loaded inside an outer tablet layer formulated to produce a pH-independent lag time prior to core drug delivery.
About Somnus Therapeutics, Inc
Somnus, with offices in Bedminster, NJ, is a private specialty pharmaceutical company founded in 2007 by Gary Cupit and Care Capital LLC, a life sciences venture capital firm. By leveraging a small team of experienced managers with an expert scientific advisory board, clinical research organizations and other outsourced services, Somnus can focus on accelerated clinical development of therapeutics for CNS markets. In February, 2010, Somnus completed a Series A preferred stock financing for approximately US$15 million, led by CTI Life Sciences Fund with the participation of Care Capital. For more information, visit the Somnus Therapeutics web site: www.somnusthera.com.
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