A new delivery method, using adhesive dermally applied microarray with zolmitriptan, appears to provide significantly better relief of migraines and bothersome migraine pain symptoms when compared to placebo.
With Peter Schmidt, MD, and Lawrence Robbins, MD
According to the National Health Interview Survey in 2015, 9.7% of men and 20.0% of women aged 18 and over reported having a migraine or severe headache in the last 3 months.1
A study published in Cephalalgia describes a new method for delivery of zolmitriptan, using an adhesive dermally applied microarray (ADAM) that achieves significantly greater relief from migraines and associated pain symptoms than placebo.4
20% of women have experienced a migraine in the past three months.
Limitations to Current Acute Migraine Treatment
Treatments for acute migraines have been available for more than a decade.2 In particular, triptans are shown to have good efficacy, tolerability, and safety.3 Until now, triptans, including zolmitriptan, have been available in a variety of delivery methods, including: 3
- Oral tablet
- Orally disintegrating tablet
- Nasal spray and powder
- Rectal suppository
- Subcutaneous delivery with or without a needle.
One challenge with many of these existing delivery methods is that migraines may be accompanied by gastric symptoms, such as nausea and gastroparesis, which may delay absorption of enterically- absorbed medications.5
In turn, this delay may slow the absorption for maximum plasma concentration and efficacy. While this limitation has b most apparent when using oral tablets, studies have shown that up to 86% of intranasal formulations may also be absorbed through the gut.6
More Reliable Administration with Disposable Patch
In a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase 2b/3 study, researchers examined the efficacy of the ADAM drug delivery system.4 ADAM is a 3 cm2disposable array of drug-coated titanium microprojections on an adhesive backing. Using an applicator to ensure consistent administration, patients were given one of the following concentrations: 1 mg, 1.9 mg, 1.9 mg (2 doses) of ADAM zolmitriptan or two ADAM placebos to treat a qualifying migraine.4
Recording headaches and symptoms in an e-diary, 360 patients recorded their level of pain and their most bothersome migraine symptom (MS) other than pain as well as their symptom scores, at set time intervals, after self-administration of either the medication or placebo. The study was designed in accordance with the FDA Guidance for Industry for acute treatment of migraine, using the co-primary endpoints of freedom from pain and freedom from MBS.4,7
Study Findings Favorable for Pain-Free Intervals
The co-primary endpoints were:
- Patients reporting freedom from the most bothersome migraine symptom
- Freedom from pain at 2 hours post-dose.
Researchers found that ADAM with zolmitriptan (3.8 mg) resulted in significantly more patients reporting being pain-free at 2 hours post-dose than placebo (41.5% vs. 14.3%; P = 0.0001) and MS-free at 2 hours (68.3% vs. 42.9%; P = 0.0009).4 ADAM with zolmitriptan (single, 1.9 mg dose) also demonstrated a significantly higher proportion of patients reporting no pain as compared to placebo (27.7% vs. 14.3%; P = 0.0351), but the MS results showed no significant difference.4
“Somewhat surprisingly, changing the pharmacokinetics and delivery route of this known drug seem to have had a significant impact on both efficacy and tolerability,” Peter Schmidt, MD, of Zosano Pharma, one of the study authors, told Practical Pain Management.
In a post-hoc analysis, pain relief from ADAM with zolmitriptan (3.8 mg) was sustained 2 to 24 hours for 68.3% of patients vs. 37.7% in the placebo group ( P = < 0.0001), pain relief lasting 2 to 48 hours was achieved for 63.4% vs. 32.5% receiving placebo (P < 0.0001).4 After examining treatment-emergent adverse events, the researchers determined that ADAM zolmitriptan was well-tolerated.
Sustained Freedom from Pain Achieved
“Given what we saw in the pharmacokinetic trial, I was concerned that pain and MBS freedom would be profound but short-lived, but this was not the case. We are now looking into receptor kinetics to see if we can understand why the sustained pain freedom percentages were so high,” said Dr. Schmidt
“These results are fairly impressive. The 2-hour pain-free result is what we’ve see with injectable sumatriptan. If approved, this skin patch of zolmitriptan will be a nice alternative for those with moderate to severe migraines,” Lawrence Robbins, MD, of the Robbins Headache Clinic in Illinois, who was not associated with the study, told Practical Pain Management.
Promising Findings for Migraine Management
The study authors concluded that ADAM with zolmitriptan @ 3.8 mg was effective and well-tolerated for the acute treatment of migraine.4 The efficacy was dose-dependent as the 3.8 mg dose provided greater relief than the 1.9 mg dose. Additionally, while no statistical analysis could be obtained on secondary endpoints, more patients wearing ADAM with zolmitriptan (3.8 mg) reported freedom from photophobia, phonophobia, and nausea as compared with the placebo group.4
“We hope that these trial results remind clinicians that despite advances in migraine prevention there is still room for improvement in the acute treatment of migraine,” said Dr. Schmidt.
Dr. Schmidt is an employee of Zosana Pharma, which funded the study. Dr. Robbins reported no financial conflicts.
- QuickStats: Percentage of Adults Aged ≥18 Years Who Reported Having a Severe Headache or Migraine in the Past 3 Months, by Sex and Age Group — National Health Interview Survey, United States, 2015. MMWR Morb Mortal Wkly Rep. 2017;66:654. DOI: http://dx.doi.org/10.15585/mmwr.mm6624a8.
- Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the American headache society evidence assessment of migraine pharmacotherapies. Headache. 2015:55(1):3-20.
- Evers S, Afra J, Frese A et al; European Federation of Neurological Societies. EFNS guideline on the drug treatment of migraine-revised report of an EFNS task force. Eur J Neurol. 2009:16(9):968-81.
- Spierings EL, Brandes JL, Kudrow DB et al. Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine. Cephalalgia. 2017.
- Volans GN. Migraine and drug absorption. Clin Pharmacokinet. 1978:3(4):313-8.
- Fuseau E, Petricoul O, Moore KH, Barrow A, Ibbotson T. Clinical pharmacokinetics of intranasal sumatriptan. Clin Pharmacokinet. 2002:41(11):801-11.
- FDA Guidance for Industry. Migraine: Developing drugs for acute treatment. Available at https://www.fda.gov/downloads/drugs/guidances/ucm419465.pdf.