ZolpiMist Oral Spray uses NovaDel’s proprietary formulation technology to deliver zolpidem tartrate, which is currently marketed as Ambien®, a leading drug from Sanofi-Aventis for the treatment of insomnia.

In June 2007, NovaDel announced positive results from its two clinical studies comparing zolpidem oral spray with Ambien® tablets. The crossover studies conducted in healthy volunteers met their primary pharmacokinetic, pharmacodynamic and safety objectives.  The results support the Company’s objective to submit a new drug application (NDA) for zolpidem oral spray using the FDA’s 505(b)(2) regulatory process.

First Study (NVD003) – Healthy volunteers with mean age of 29 years
Study NVD003 compared 5 mg and 10 mg doses of zolpidem oral spray with comparable doses of Ambien® tablets.  Pursuant to FDA guidance in this type of 4-way crossover study, all data were compared to the highest marketed dose, which in this study was the 10 mg Ambien® tablet.  Positive results from the study demonstrated that NovaDel’s 10 mg and 5 mg oral sprays achieved bioequivalence with 10 mg Ambien® tablets, the primary standard of reference for this study.

A secondary assessment of the relationship between speed of drug absorption and the attainment of  therapeutic drug levels showed 79% of subjects using the 10 mg zolpidem oral spray reached therapeutic levels at 15 minutes post-dosing while only 26% of subjects using 10 mg tablets reached therapeutic levels at that time point. The results were statistically significant.

Second Study (NVD004) – Healthy, elderly volunteers with mean age of 71 years
Study NVD004 compared doses of 5 mg zolpidem oral spray to 5 mg Ambien® tablets. The primary objective of the study was to demonstrate comparability/bioequivalence of pharmacokinetics between oral spray and tablet groups. 

A secondary assessment of the relationship between speed of drug absorption and the attainment of therapeutic drug levels showed 65% of subjects using the 5 mg zolpidem oral spray reaching therapeutic levels at 15 minutes post-dosing while only 19% of subjects in the tablet group reached therapeutic levels by 15 minutes. The results were statistically significant.

Current Status
Additional data from the studies also suggest that NovaDel’s oral spray technology may provide earlier therapeutic drug concentrations and a more rapid pharmacodynamic effect, even while administering lower doses.  Using the pharmacokinetic results as the clinical requirements for the FDA’s 505(b)(2) process and pending the successful completion of all manufacturing, safety and regulatory work, the Company intends to submit its NDA for zolpidem oral spray in the second half of 2007.

About Insomnia
Insomnia is a sleep disorder whose sufferers experience inadequate or poor quality sleep and report one or more of the following: difficulty initiating sleep, difficulty maintaining sleep, and waking up too early. According to the “2005 Sleep in America Poll,” 54% of those surveyed indicated they experience at least one symptom of insomnia a few nights per week. Only approximately 14% of the respondents reported using any sort of sleep-aid therapy. Walsh and Engelhardt (1999) estimated $14 billion is spent each year on the direct costs of insomnia, including pharmaceuticals, healthcare services and hospital and nursing home care. Cowen & Company estimated the total non-benzodiazepine prescription market in the U.S. for the treatment of insomnia in 2006 was approximately $3.4 billion, growing to $3.8 billion by 2011. Ambien®/Ambien CR™ (zolpidem tartrate) are the dominant products with approximately 80% of the market in 2006. The patent on Ambien® has expired and generic products were recently introduced.

Imitrex®, Zofran® and Requip® are registered trademarks of GlaxoSmithKline. Ambien® is a registered trademark of Sanofi-Aventis. Zanaflex® is a registered trademark of Acordia Therapeutics Inc. ZolpiMist™ and NitroMist™ are trademarks of NovaDel Pharma, Inc. Zensana™ is a pending trademark of Hana Biosciences.