Crossover Comparison of the Tolerability and Pharmacokinetics of ZP-Zolmitriptan Intracutaneous Microneedle System with Oral Zolmitriptan and Subcutaneous (SC) Sumatriptan in Healthy Volunteers

INTERVENTION: In this study, ZP‐Zolmitriptan will be compared to oral zolmitriptan and SC sumatriptan. ZP‐Zolmitriptan is a microneedle patch system consisting of a disposable microneedle patch and a reusable applicator. The user applies the patch by pressing the applicator/patch ring assembly onto the skin site on the upper arm. The ZP applicator is designed to ensure that the same force is applied across different users. Each of the 20 subjects will receive each of the treatments once (A‐G) every 5 days i.e. 120 hours between dosing days. In Part 1, each of the subjects will be randomly assigned to one of the five treatments (A‐E) on the first dosing day. On the second dosing day, they will be randomly assigned to one of the remaining four treatments. On dosing days 3,4, and 5, they will be randomly assigned to one of the other remaining treatments until all five treatments (A‐E) have been taken by each of the subjects. On any dosing day, for the 20 subjects, four will receive Treatment A, four will receive Treatment B, four will receive Treatment C, four will receive Treatment D, and four will receive Treatment E. Treatment A: ZP‐Zolmitriptan intracutaenous system MF 1663 0.48 mg Treatment B: Two patches of ZP‐Zolmitriptan intracutaenous system MF 1663 0.48 mg Treatment C: ZP‐Zolmitriptan intracutaenous system MF 1663 1.9 mg Treatment D: Zolmitriptan 2.5 mg tablet Treatment E: Sumitriptan Succinate 6.0 mg/0.5 mL for SC injection In Part 2, all subjects will receive Treatment F (ZP‐Zolmitriptan intracutaenous system MF 1663 1.9 mg x2). Treatment F: Two patches of ZP‐Zolmitriptan intracutaenous system MF 1663 1.9 mg In Part 3, all subjects will receive Treatment G (ZP‐Zolmitriptan 3.8 mg). Treatment G: ZP‐Zolmitriptan intracutaenous system MF 1790 3.8 mg For each treatment, drug is administered once. Treatments B and F consist of two patches that should be applied on the same arm as quickly as possible. All drug administration and application is done by the site staff. At the end of each dosing day, the safety data from the subjects will be evaluated. If tolerability is deemed to be acceptable by the Principal Investigator and sponsor representatives, a decision will be made to proceed to the next dosing day. CONDITION: Migraine SECONDARY OUTCOME: Compare the pharmacokinetic profiles of Zolmitriptan‐ZP Intracutaneous Microneedle systems (particularly Cmax) with oral zolmitriptan and SC sumatriptan. The following pharmacokinetic parameters will be calculated for each treatment ‐ AUC0‐t, AUC0‐inf, AUC30min, Cmax, Tmax and t1/2. INCLUSION CRITERIA: 1) Women or men 18 to 60 years of age 2) Absence of significant health issues 3) Systolic BP (measured after remaining supine for 5 minutes) inclusive of 90 and 160 mmHg and diastolic BP inclusive of 50 and 95 mmHg. 4) Body mass index (BMI) of less than or equal to 32 kg/m2 All ZP‐Zolmitriptan Patch System components are to be used only in accordance with this protocol under the supervision of the Investigator. The Investigator will maintain detailed and verifiable records that document the receipt, storage, dispensing, and return of all ZP‐Zolmitriptan Patch System components provided by Zosano Pharma. These records will include a listing of which study drug supplies were dispensed for particular subjects treated in the study, by whom, when, and the specific quantities dispensed and remaining at the completion of the subject’s investigational treatment. Reasons for departure from the expected dispensing and dosing regimen will also be documented. All leftover used and unused study patches should be retained for drug accountability auditing to be performed by Zosano Pharma or its representatives. At the conclusion of the study, the study drug accountability records must accurately reflect the receipt and final disposition of all study drug shipped to the site. Destruction or return of remaining used and unused drug supplies by the study site will occur only upon receipt of written authorization by Zosano Pharma or its representatives. PRIMARY OUTCOME: Determine the bioavailability of Zolmitriptan‐ZP intracutaenous systems relative to a conventional release 2.5 mg Zolmitriptan tablet. Blood samples and analysed to calculate both mean and median values for each treatment. Pharmacokinetics of ZP‐Zolmitriptan Intracutaneous Microneedle systems. Plasma zolmitriptan concentrations as a function of time following ZP‐Zolmitriptan patch administration will be plotted and cross‐compared among treatments. The following pharmacokinetic parameters will be calculated for each treatment ‐ AUC0‐t, AUC0‐inf, AUC30min, Cmax, Tmax and t1/2. Tolerability of ZP‐Zolmitriptan Intracutaneous Microneedle systems. Tolerability will assessed through visual assessments of the application sites for erythema, edema, patch‐related superficial punctuate bruising and bleeding. Adverse events are also recorded. The safety data, including AEs, laboratory data, vital signs, ECGs, concomitant medications, and reasons for withdrawal from study, will be listed and/or descriptively summarized by treatment dose and patch application subgroup.