Nasal powder formulation of sumatriptan bests oral tablets in reducing nausea

Compared with oral sumatriptan, AVP-825—a nasal powder formulation and delivery system of sumatriptan—led to more favorable nausea outcomes, more rapid reductions in nausea in the first hour after dosing, and reduced both the odds of nausea and the risk of treatment-emergent nausea (TEN), according to an analysis of data from the COMPASS trial. Results were published in Headache.

“Migraine-related nausea is associated with significant disability, increased burden of disease, and personal distress. Nausea can lead to delays or avoidance of initiating oral migraine treatment, sometimes resulting in treatment failures and poor outcomes. Nausea is often a symptom of migraine, but nausea may also be a consequence of treatment (ie, treatment emergent nausea). Relieving nausea and minimizing TEN are important goals in acute migraine therapy,” wrote the authors, led by Richard B. Lipton, MD, Department of Neurology, Albert Einstein College of Medicine and Montefiore Headache Center, Bronx, NY.

Although triptans are effective and the most commonly used medication for the acute treatment of migraine, they are associated with TEN. Accordingly, migraine treatment guidelines recommend non-oral formulations for migraines associated with nausea and vomiting.

AVP-825 is a non-oral delivery system for sumatriptan that contains 22 mg sumatriptan in a dry powder formulation. The intranasal system uses the patient’s breath to deliver the medication to the upper posterior nasal cavity. The pharmacokinetics of AVP-825 show that, compared with sumatriptan in both the 100-mg oral tablet and the 20-mg nasal spray formulations, it has a shorter time to maximal plasma concentration and greater exposure in the first 15 minutes. Thus, AVP-825 may more efficiently deliver sumatriptan for quicker migraine relief.

Dr. Lipton and colleagues compared AVP-825 with oral sumatriptan tablets (100 mg) using data from the COMPASS study, a randomized, double-blind, double-dummy, comparative efficacy study conducted at 20 outpatient headache centers throughout the United States from August 2012 to March 2014.

Patients were randomized 1:1 to one of two blinded treatment sequences, each broken down into two 12-week periods. Sequence 1 was comprised of treatment for up to five attacks with AVP-825 and a placebo tablet. After five attacks (or 3 months), the second treatment period was initiated, and was comprised of placebo containing lactose powder and sumatriptan in tablet form (100 mg). Subjects in sequence 2 were treated in reverse treatment order.

The study protocol specified that treatment be administered within 1 hour of migraine onset. Subjects were required to record outcomes for each migraine in an electronic diary.

All patients had monthly migraines that were moderate in intensity over the previous 12 months. Their mean age was 40 years, 12%-16% were male, and 78%-79% were white. Only 52%-55% reported taking medication for moderate-to-severe migraine pain intensity.

Dr. Lipton and colleagues used three-level logistic models to assess changes in nausea brought about by AVP-825 and oral sumatriptan. In model 1 (n=259), they assessed overall nausea using longitudinal change in nausea before and for 120 minutes after dosing. In model 2 (n=232), they assessed TEN from 10-120 minutes in migraines free of nausea to identify whether nausea developed after treatment. Finally, in Model 3 (n=167), researchers assessed nausea relief during the 2 hours after dosing.

They found that in Models 1 and 2, longitudinal nausea trajectories differed. In Model 3, however, nausea relief was similar.

In Model 1, patients treated with AVP-825 experienced significantly faster relief of nausea during the first 60 minutes after dosing. Treatment with AVP-825 also reduced the odds of nausea at each time point from 30-120 minutes after dosing compared with oral sumatriptan.

In Model 2, patients treated with oral sumatriptan had an increased risk for TEN during the first 45 minutes after dosing, as well as significantly greater odds of TEN at 45 through 90 minutes after dosing.

In Model 3, researchers observed similar rates in change in nausea over time for both treatments, but a constant difference in the levels of nausea, which led to reduced odds of nausea in those treated with AVP-825.

The results highlight the importance of separate assessments of TEN and nausea relief.

“The results of this study combined with previous research may help clinicians optimize migraine treatment. Oral sumatriptan causes TEN while non-oral sumatriptan, whether administered by injection, cutaneous patch, or breath-powered intra-nasal delivery appears less likely to cause TEN. Results showed that nausea risk varied substantially across subjects and attacks,” concluded Dr. Lipton and fellow researchers.