A Study of M207 With Intranasal Zolmitriptan in Healthy Volunteers
Condition: Migraine
Intervention: A: M207 3.8mg, 30 min, upper arm; B: M207 3.8 mg, 30 min, thigh; C: M207 3.8 mg, 1 hr, upper arm; D:zolmitriptan nasal spray
Intervention description: A: M207 3.8 mg administered as two 1.9 mg patches, 30 min wear time (upper arm application); B: M207 3.8 mg administered as two 1.9 mg patches, 30 min wear time (thigh application); C: M207 3.8 mg administered as two 1.9 mg patches, 1 hour wear time (upper arm application); D: 2.5 mg/0.1 mL intranasal zolmitriptan
Intervention MeSH terms: Oxazolidinones; Zolmitriptan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized, open-label four-way crossover
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy; Volunteer; Pharmacokinetics

Summary:

      This is a single-center, open-label, randomized, four-way crossover study. Each subject will
      receive each of the four study treatments once, followed by in-clinic monitoring and
      extensive blood sample collection for pharmacokinetic analysis.

      Dosing will occur approximately 48 hours apart, until completion of dosing in randomized
      order per the treatment sequence tables. Plasma samples from the dosing days will be sent to
      the analytical laboratory for analysis and tolerability for each of the dose levels will be
      summarized.

      After completion of the four dosing days, subjects will be assessed one final time and
      dismissed from the study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Women or men 18 to 50 years of age.

          2. Good general health with no clinically significant abnormalities as determined by
             medical history, physical examination, complete blood count (CBC), blood chemistry,
             urinalysis, and ECG.

          3. Negative urine drug and alcohol screens and negative serum pregnancy tests (for female
             subjects) at screening.

          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), condom
             and vaginal spermicide, hormonal contraceptives (subjects must be stable on hormonal
             contraceptives for at least the prior 3 months), surgical 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 two or more risk factors for cardiovascular disease (family history of
             premature heart disease, hyperlipidemia, or hypertension)

          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

               -  Peripheral Vascular Disease

               -  Ischemic bowel disease

               -  Uncontrolled hypertension

               -  Any history of hepatic impairment

          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 screening
             through their last day of study participation

          6. Use of warfarin within 1 month prior to the first dose or heparin within 1 week prior
             to study drug administration

          7. Use of prescription and over the counter medications other than the following:

               -  Hormone Replacement Therapy (HRT)

               -  Birth control pills, patches, injections, or implants (all hormonal
                  contraceptives) are allowed provided the dose has been stable for at least one
                  month prior to screening and may be continued throughout the study

               -  Antihistamines

               -  Intermittently used NSAIDS

               -  Acetaminophen if medically necessary (not more than 2 g/day)

               -  Exceptions may be allowed on a case by case basis

          8. Subjects who have a known allergy or sensitivity to zolmitriptan or its derivatives or
             formulations

          9. Known allergy or sensitivity to tapes, adhesives, or zolmitriptan

         10. Regular or recent intake of prescription drugs, particularly drugs with an influence
             on blood pressure.

         11. Use of any other investigational compound within one month of planned study drug
             dosing

         12. On-going drug or alcohol abuse, or history of either deemed to be clinically
             significant by the investigator

         13. Systolic BP (measured after remaining sitting for 5 minutes) greater than 140 mmHg and
             diastolic BP greater than 90 mmHg at screening

         14. History of nasal pathology (e.g., polyps) or abnormal nasal exam

         15. Body Mass Index (BMI) greater than 35 kg/m2

         16. If, in the opinion of the investigator, the subject is not suitable for the study

         17. Any positive urine drug screen result or alcohol breath test