Zelrix™: A Novel Transdermal Formulation of Sumatriptan

Authors

  • Mark Pierce MD, PhD,

    1. From the University of Pennsylvania – Psychiatry, Philadelphia, PA, USA (S. Siegel); NuPathe – Research and Development, Conshohocken, PA, USA (M. Pierce, T. Marbury, C. O'Neill, W. Du, and T. Sebree).
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  • Thomas Marbury MD,

    1. From the University of Pennsylvania – Psychiatry, Philadelphia, PA, USA (S. Siegel); NuPathe – Research and Development, Conshohocken, PA, USA (M. Pierce, T. Marbury, C. O'Neill, W. Du, and T. Sebree).
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  • Carol O'Neill BA,

    1. From the University of Pennsylvania – Psychiatry, Philadelphia, PA, USA (S. Siegel); NuPathe – Research and Development, Conshohocken, PA, USA (M. Pierce, T. Marbury, C. O'Neill, W. Du, and T. Sebree).
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  • Steven Siegel MD, PhD,

    1. From the University of Pennsylvania – Psychiatry, Philadelphia, PA, USA (S. Siegel); NuPathe – Research and Development, Conshohocken, PA, USA (M. Pierce, T. Marbury, C. O'Neill, W. Du, and T. Sebree).
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  • Wei Du PhD,

    1. From the University of Pennsylvania – Psychiatry, Philadelphia, PA, USA (S. Siegel); NuPathe – Research and Development, Conshohocken, PA, USA (M. Pierce, T. Marbury, C. O'Neill, W. Du, and T. Sebree).
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  • Terri Sebree BA

    1. From the University of Pennsylvania – Psychiatry, Philadelphia, PA, USA (S. Siegel); NuPathe – Research and Development, Conshohocken, PA, USA (M. Pierce, T. Marbury, C. O'Neill, W. Du, and T. Sebree).
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  • Financial Support: This work was sponsored by NuPathe Inc.

  • Conflict of Interest: Dr. Pierce, Ms. O'Neill, and Ms. Sebree are employees of NuPathe. Dr. Marbury is an employee of Orlando Clinical Research Center. Drs. Siegel and Du are consultants to NuPathe.

M. Pierce, NuPathe Inc., 227 Washington Street, Suite 200, Conshohocken, PA 19428, USA.

Abstract

Objective.— This study evaluated the pharmacokinetic and tolerability profiles of Zelrix™ (NuPathe Inc., Conshohocken, PA, USA), the novel formulation of sumatriptan (formerly known as NP101).

Background.— Migraine is an episodic headache disorder characterized by a combination of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal disturbances, including nausea, vomiting, and gastric stasis are common and can result in significant impact on treatment. Triptans are 5-hydroxytriptanime1B/1D agonists that work on the trigeminal nerve that is activated during migraine. All triptans approved for use in the US are currently available as oral formulations; however, this may not be the ideal route of administration for many migraineurs. Sumatriptan is also available as a nasal spray and subcutaneous (sc) injection. Therefore, the need to develop improved methods for noninvasive parenteral delivery of triptans remains high.

Methods.— This was a Phase I, single-center, open-label, crossover study that assessed the pharmacokinetic properties of a single dose of sumatriptan delivered using an iontophoretic transdermal patch in comparison with oral, injection, and nasal delivery. Subjects were healthy male and female volunteers who received each of 5 treatments: sumatriptan 100 mg oral tablets, sumatriptan 6 mg sc, sumatriptan 20 mg nasal spray, Zelrix I (transdermal patch with 3 g of gel solution delivering 6 mg of sumatriptan transdermally), or Zelrix II (transdermal patch containing 2.6 g of gel solution delivering 6 mg of sumatriptan).

Results.— The Cmax for Zelrix was reduced to 30% and 28% of the sumatriptan sc dose, thereby reducing the risk of triptan-like sensations associated with high peak plasma concentrations. Plasma concentrations for Zelrix I and Zelrix II were intermediate between those for oral and nasal sumatriptan doses tested. Transdermal patch delivery of sumatriptan to the systemic circulation reached plasma concentrations of 10 ng/mL within about 30 minutes. The mean drug delivery of Zelrix I and II was 6.11 mg (confidence intervals [CI] 5.33-6.88) and 6.09 mg (CI 5.52-6.66), respectively. The AUC0-inf was approximately 99% for the Zelrix I patch and 100% for the Zelrix II patch as compared with sumatriptan 6 mg sc dose. Both doses of sumatriptan transdermal patches were well tolerated. Skin reactions at the patch site were mild and erythema resolved in most subjects within 48-72 hours.

Conclusions.— The results from this study show that sumatriptan administration using a novel iontophoretic transdermal technology delivers plasma levels within the range for nasal spray, tablet, and injectable sumatriptan. Zelrix I and II were well tolerated and adverse events were mild and transient. Transdermal delivery of sumatriptan using the SmartRelief iontophoretic technology may prove beneficial for a large segment of the migraine population based upon fast, consistent delivery of drug and avoidance of common gastrointestinal disturbances associated with migraine.

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