Mohammad Obaidi, PhD; Elliot Offman, BSc, Pharm MSc; John Messina, PharmD; Jennifer Carothers, ScD; Per G. Djupesland, MD, PhD; Ramy A. Mahmoud, MD, MPH
Introduction
A prior PK study found that low doses of sumatriptan powder delivered intranasally with a Breath Powered device were efficiently and rapidly absorbed. An early phase clinical trial with the same device and doses found excellent tolerability with high response rates and rapid onset of pain relief, approaching the benefits of injection despite significantly lower predicted drug levels.
Methods
- A randomized open-label, cross-over, comparative bioavailability study was conducted in 20 healthy subjects at a single center in the USA
- Following randomization, fasted subjects received a single dose of each of the following treatments AVP-825 (OptiNose device delivering sumatriptan powder), Imitrex® 20 mg liquid nasal spray, Imitrex® 100 mg oral tablet and Imitrex® 6 mg subcutaneous injection, each separated by a 7-day washout.
- Blood samples were taken pre-dose and serially over 14 hours post-dose for PK analysis.
Results
- Quantitative measurement of residuals in used Breath Powered devices demonstrated that the devices delivered 8 ± 0.9 mg (mean ± standard deviation) of sumatriptan powder in each nostril (total dose 16 mg)
- Although the extent of systemic exposure over 14 hours was similar following Breath Powered delivery of 16-mg sumatriptan powder and 20-mg liquid nasal spray (area under the curve [AUC 0-∞ ] 64.9 ng*hour/mL vs. 61.1 ng*hour/mL), sumatriptan powder, despite a 20% lower dose, produced 27% higher peak exposure (Cmax 20.8 ng/mL vs. 16.4 ng/mL) and 61% higher exposure in the first 30 minutes compared with the nasal spray (AUC 0-30 minutes 5.8 ng*hour/mL vs. 3.6 ng*hour/mL)
- On a dose adjusted (per-milligram of drug delivered to the patient) basis this represents a 59% higher peak exposure and 100% higher early exposure.
- The absorption profile of standard nasal spray showed bimodal peaks, consistent with lower early followed by higher later absorption
- In contrast, the profile following Breath Powered delivery showed higher early and lower late absorption peaks
- The peak and overall drug exposure following Breath Powered intranasal delivery of sumatriptan powder was substantially lower than the 100-mg oral tablet (Cmax 70.2 ng/mL,AUC0-∞,308.8 ng*hour/mL) and 6-mg injection (Cmax 111.6 ng/mL,AUC 0-∞ 128.2 ng*hour/mL)
Conclusions
Breath Powered intranasal delivery of sumatriptan powder is a more efficient form of drug delivery, producing a higher peak and earlier exposure with a lower delivered dose than nasal spray, and faster absorption than either nasal spray or oral administration. It also produces a significantly lower peak and total systemic exposure than oral tablet or subcutaneous injection.
Clinical Data
Data was published in the September 2013 issue of Headache ISSN 0017-8748, the official journal of the American Headache Society