ONZETRA™ Xsail™ (sumatriptan nasal powder)

Please see Instructions For Use and full Prescribing Information at www.ONZETRA.com

Important Safety Information

What is ONZETRA® Xsail® (sumatriptan nasal powder) used for?
ONZETRA Xsail is a prescription medication approved for the acute treatment of migraine, with or without aura in adults. ONZETRA Xsail is used for people who have been told by a healthcare provider that they have migraine headaches. ONZETRA Xsail is not for the prevention of migraines or for other types of headaches, including cluster headache.

What important information should I know about ONZETRA Xsail?
ONZETRA Xsail may cause serious side effects, including:

  • Heart attack and other heart problems, which may lead to death. Stop using ONZETRA Xsail and get emergency medical help right away if you have any symptoms of a heart attack like shortness of breath or tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw that is severe or does not go away
  • Changes in color or sensation in your fingers and toes (Raynaud’s syndrome)
  • Stomach and intestinal problems (gastrointestinal and colonic ischemic events)
  • Problems with blood circulation to your legs and feet (peripheral vascular ischemia)
  • Serious allergic reactions (symptoms include hives; tongue, mouth, lip, or throat swelling; problems breathing)
  • Medication overuse headaches. Some people who use ONZETRA Xsail too many times may have worse headaches. If your headaches get worse your doctor may decide to stop your treatment with ONZETRA Xsail
  • Serotonin syndrome, a rare but serious problem that can happen in people using ONZETRA Xsail, especially if ONZETRA Xsail is used with antidepressant medicines called SSRIs, SNRIs, or TCAs. Call your doctor right away if you have any of the following symptoms of serotonin syndrome: mental changes such as seeing things that are not there (hallucinations), agitation, or coma; fast heartbeat; changes in blood pressure; high body temperature; tight muscles; trouble walking; or nausea, vomiting, or diarrhea
  • Seizures. Seizures have happened in people taking sumatriptan who have never had seizures before

The most common side effects of ONZETRA Xsail are abnormal taste, discomfort of your nose or throat, runny nose, and stuffy nose. This is not a complete list of side effects. Tell your doctor about any side effect that bothers you or does not go away.

Who should not take ONZETRA Xsail?
Do not take ONZETRA Xsail or stop using ONZETRA Xsail if you:

  • Have heart problems or a history of heart problems
  • Have had a stroke, transient ischemic attacks (TIAs), or problems with your blood circulation
  • Have uncontrolled high blood pressure
  • Have hemiplegic migraines or basilar migraines. If you are not sure if you have these, ask your doctor
  • Have peripheral vascular disease (narrowing of blood vessels to the legs, arms, stomach, intestines, or kidneys)
  • Have taken other migraine medications in the last 24 hours, including other triptans, ergots, or ergot-type medications. Ask your doctor for a list of these medicines if you are not sure
  • Are taking a medicine called a monoamine oxidase inhibitor (MAOI). MAOIs cannot be taken within 14 days before or after taking ONZETRA Xsail
  • Have severe liver problems
  • Have an allergy to sumatriptan, the medicine in ONZETRA Xsail, or any of the components in ONZETRA Xsail

What should I tell my healthcare provider before taking ONZETRA Xsail?
Before you take ONZETRA Xsail, tell your doctor about all your medical conditions and all the medicines you take, including prescription medicines, especially antidepressants, and all over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while taking ONZETRA Xsail?
ONZETRA Xsail can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 800-FDA-1088.

For additional Important Safety Information about ONZETRA Xsail, please see the full Prescribing Information, including Patient Information and Instructions for Use.

Trial Rationale

Approximately 28 million people in the United States live with migraine[1], with a prevalence of 18.2% among females and 6.5% among males. In a study, half of the participants reported that headaches were severe enough to affect their school and work productivity. With migraine costs estimated to be $13 to $17 billion per year in the United States alone, improved therapies to speed relief and reduce pain reduction are desirable.

Tablets may less effective than parenteral therapies in treating migraine because gastric emptying is delayed during attacks. Intranasal formulations of some triptans (sumatriptan, zolmitriptan) have been developed with the intent of achieving faster onset of action while avoiding the need to inject the drug. However, inherent challenges associated with traditional nasal sprays remain.

AVP-825, low-dose sumatriptan combined with OptiNose patented Bi-Directional™ Breath Powered® technology for intranasal delivery, has been studied for its potential to reduce migraine pain in preclinical, Phase III and head-to-head comparative trials. Brief overviews of each of the trials are included below and some PDFs with full study data are available for download.

Phase III: Completed

TARGET: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Evaluating the Efficacy and Safety of a Single 20 mg Dose of Sumatriptan Powder Delivered Intra-nasally with the Bi-Directional Device in Adults With Acute Migraine With or Without Aura

This Phase III study of 230 adults used acute treatment of a single migraine attack to assess the ability of AVP-825 (16mg sumatriptan) to provide headache relief at 120 minutes.

Migraine sufferers were randomized to self-administer either AVP-825 or placebo using the Breath Powered device when they had moderate to severe migraine pain. Pain was evaluated using a four-point scale with headache relief defined as a reduction from moderate (grade 2) or severe (grade 3) pain to mild (grade 1) or complete relief (grade 0). The data showed pain relief for some subjects began as early as 15 minutes after treatment, and a statistically significant greater number of subjects receiving AVP-825 experienced headache relief compared to placebo at all times from 30 minutes through two hours.

Specifically:

  • AVP-825 provided headache relief for 68% of patients with moderate to severe migraines after two hours (p<0.01 compared to placebo).
  • Participants began to experience headache relief as quickly as 15 minutes after administration, with nearly 42% reporting pain relief at 30 minutes post-treatment.
  • At two hours after taking the medication, 70% of subjects taking OptiNose sumatriptan (AVP-825) reported that they were experiencing meaningful relief from their headache pain.
  • There were no serious adverse events associated with OptiNose sumatriptan (AVP-825) in the study. There were also no systemic adverse events reported in more than a single subject, and local adverse events reported in the nose were generally mild and transient.

Head-to-Head Comparison Trial: COMPASS: Efficacy and Safety of 20 mg Sumatriptan Powder Delivered Intranasally With the Bi-Directional Device Compared With 100 mg Sumatriptan Tablets in Adults With Acute Migraine With or Without Aura

This Phase III study compared the use of AVP-825 (22mg) to the highest approved dose (100mg) of sumatriptan tablets, currently the most widely used prescription medication for migraine. The double-blind, double-dummy, cross-over design involved 275 adults and showed that AVP-825 provided an earlier reduction in pain than oral sumatriptan, with headache relief beginning as early as 15 minutes. Specifically:

  • During the first 30 minutes, headache pain intensity was statistically significantly lower with AVP-825 treatment.
  • The trial achieved statistical significance for relevant secondary measures of Pain Relief and Pain Freedom as early as 15 minutes and at all of the following early time points measured (30, 45, 60, 90) before 120 minutes.

The overall safety profile of AVP-825 was consistent with that observed in previous trials. Fewer than two percent of subjects experienced an adverse event leading to treatment discontinuation with use of either medication, and there were no serious adverse events. Nasal discomfort and abnormal product taste were more common with AVP-825 administration; these adverse events were deemed mild in nearly 90% of cases.

Phase II: Completed

Intranasal sumatriptan powder delivered by a novel breath-actuated bi-directional device for the acute treatment of migraine: A randomized, placebo-controlled study

This multicenter, parallel group, placebo-controlled study involved 117 adults in whom a single (moderate or severe) migraine attack was treated in-clinic with sumatriptan 10mg, sumatriptan 20mg or placebo delivered via the OptiNose device. The study showed that those patients who received sumatriptan via the OptiNose device reported significantly greater pain relief at both 60 and 120 minutes and were sustained pain-free up to 48 hours after use.

Specifically:

  • A greater proportion of subjects who received sumatriptan were pain-free at 120 minutes compared with those who received placebo
  • Significant benefits were also observed for pain relief at 120 minutes and as early as 60 minutes, and for 48 hours sustained pain-free
  • Treatment-related adverse events were rare, with a metallic taste being the one most commonly reported

Read abstract from CEPHALALGIA, MARCH 2010

pain_60_120_placebo

[1] American Migraine Study (AMS) II