This is a single-center, open-label, randomized, 3-way crossover study. Each subject will receive each of the three study treatments once, followed by in-clinic monitoring and extensive blood sample collection for plasma PK analysis.

Dosing will occur at least 48 hours apart from the time of patch application, until completion of dosing in randomized order per the treatment sequence schedule. After completion dosing, subjects will be assessed one final time.

This is a single-center, open-label, randomized, three-way crossover study. Each subject will receive each of the three study treatments once, followed by in-clinic monitoring and extensive blood sample collection for pharmacokinetic analysis.

Dosing will occur at least 48 hours apart from the time of patch application, until completion of dosing in randomized order per the treatment sequence schedule. Subjects may be dosed in 2 or more separate groups in each period, for example, 24 subjects on one day and 24 subjects on another day.

Plasma samples from the dosing days will be sent to the analytical laboratory for analysis. Tolerability scores for each of the dose levels will be summarized.

After completion of the three dosing days, subjects will be assessed one final time and dismissed from the study.

Inclusion Criteria:

1. Women or men 18 to 50 years of age (inclusive)
2. Good general health with no clinically significant abnormalities as determined by medical history, physical examination, CBC, blood chemistry, urinalysis, and ECG.
3. Negative serum pregnancy tests (for female subjects) at the screening and admission visit.
4. Consent of female subjects to use a medically effective method of contraception throughout the entire study period and for 30 days after the subject completes the study. Medically effective methods of contraception that may be used by the subject include abstinence, use of diaphragm and spermicide, intrauterine device (IUD), rings, condom and vaginal spermicide, non-oral hormonal contraceptives (subjects must be stable on non-oral hormonal contraceptives for at least 3 months prior to screening), surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy, hysteroscopic sterilization) and post-menopausal (≥ 2 years of amenorrhea).
5. Ability to read, understand, and provide written informed consent that they understand the purpose of the study and procedures required for the study before enrolling in the study, and willingness to comply with all study procedures and restrictions.

Exclusion Criteria:

1. Evidence of significant history of hepatic, reproductive, gastrointestinal, renal, bleeding, or hematological disorders including coagulation, pulmonary, neurological, respiratory, endocrine, or cardiovascular system abnormalities (especially hypertension, peripheral vascular disease, coronary artery disease, transient ischemic attacks, or cardiac rhythm abnormalities), psychiatric disorders, acute infection, or other conditions that would interfere with study participation or with the absorption, distribution, metabolism, or excretion of drugs.

2. Presence of three or more of the following CAD risk factors for cardiovascular disease:

   A. Current tobacco use (subjects who have smoked within 30 days of screening) B. Hypertension (systolic BP > 140 or diastolic BP > 90) or receiving anti-hypertensive medication for treatment of hypertension C. Hyperlipidemia - LDL > 159 mg/dL and/or HDL < 40 mg/dL (or on prescribed anti-cholesterol treatment) D. Family history of premature coronary artery disease (CAD) (< 55 years of age in male first-degree relatives or < 65 years of age in female first degree relatives) E. Diabetes mellitus

3. Any contraindication to zolmitriptan administration including:

   • History of coronary artery disease or coronary vasospasm
   • Symptomatic Wolf-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders
   • History of stroke, transient ischemic attack, or hemiplegic or basilar migraine
   • History or current Peripheral Vascular Disease
   • History or current Ischemic bowel disease
   • Hypertension (greater than or equal to 140/90 mmHg at either the screening or admission/baseline visit
   • Any history of hepatic impairment defined as ALT > 150 U/L, AST > 130 U/L or bilirubin > 2 times the ULN

4. History of contact dermatitis or known dermatological disorders that would interfere with the study procedures or assessments

5. Planned participation in activities which cause inflammation, irritation, sunburn, lesions, or tattoos at the intended application sites from 2 weeks prior to dosing through the duration of the trial

6. Use of any prescription anticoagulant within 30 days prior to the first dose through the duration of the trial

7. Use of prescription and over the counter medications within one week of dosing other than the following:

   • Hormone Replacement Therapy (HRT)
   • Non-oral hormonal birth control such as patches, IUD, rings, injections, or implants (all non-oral hormonal contraceptives) are allowed provided the dose has been stable for at least three months prior to screening and may be continued throughout the study
   • Antihistamines
   • Intermittently used NSAIDS
   • Acetaminophen if medically necessary (not more than 1000 mg/day)

8. Current known allergy or sensitivity to zolmitriptan or its derivatives or formulations

9. Current known allergy or sensitivity to tapes or adhesives

10. Use of any other investigational compound within 30 days of planned study drug dosing

11. Current use or history of drug and/or alcohol abuse within 6 months of screening and deemed to be clinically significant by the investigator

12. History of nasal pathology (e.g., polyps, significant septal deviation or perforation) or abnormal nasal exam (with findings such as nose piercing, gross deformities, and/or severe congestion) deemed to be clinically significant by the investigator

13. Body Mass Index (BMI) lower than 18 kg/m2 or greater than 35 kg/m2

14. In the opinion of the investigator, the subject is not suitable for the study

15. Any positive urine drug result or alcohol test at screening or admission, and/or a positive COVID-19 test performed at admission.

16. Any planned COVID-19 vaccination within a week of dosing through the duration of the trial

17. Currently a smoker or a nicotine user