A Four-way Crossover Study of 3 Formulations of M207 With Intranasal Zolmitriptan in Healthy Volunteers
Condition: Migraine
Intervention: M207 3.8 mg "Sled" (two 1.9 mg patches made on a "Sled" coater, foil pouches); M207 3.8 mg "MACAP" (two 1.9 mg patches made on a "MACAP" coater, foil cups); M207 3.8 mg "MiniMac" (two 1.9 mg patches made on a "MiniMac" coater, foil cups; Zolmitriptan 2.5 mg/0.1 mL nasal spray [ZOMIG] single dose
Intervention description: M207 3.8 mg administered as two 1.9 mg upper arm patches 30 min wear time made on a "Sled" coater and packaged in foil pouches; M207 3.8 mg administered as two 1.9 mg upper arm patches 30 min wear time made on a "MACAP" coater and packaged in foil cups; M207 3.8 mg administered as two 1.9 mg upper arm patches 30 min wear time made on a "miniMac" coater and packaged in foil pouches; Zolmitriptan 2.5 mg/0.1 mL nasal spray [ZOMIG] single dose
Intervention MeSH terms: Zolmitriptan
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects are randomized to receive one of four treatment sequences of four open-label treatments 48 hours apart.
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacokinetics; Healthy; Volunteer

Summary:

      This is a single-center, open-label, randomized, four-way crossover study. Subjects will
      receive the four study treatments once, followed by in-clinic monitoring and extensive
      pharmacokinetic analysis. Dosing occurs ~48 hours apart from patch application, in randomized
      order. Subjects will have final assessment and be dismissed from the study.
    

Eligibility criteria:

        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, complete blood count, blood chemistry,
             urinalysis, and ECG.

          3. Negative urine drug and alcohol screens and negative serum pregnancy tests (for female
             subjects) at screening and admission/baseline 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, hormonal contraceptives (subjects must be stable on
             hormonal contraceptives for at least 3 months prior to screening), surgical
             sterilization (hysterectomy, bilateral tubal ligation, 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

               -  Peripheral Vascular Disease

               -  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 alanine transaminase > 150 U/L,
                  aspartate aminotransferase > 130 U/L or bilirubin > 2 times the upper limit of
                  normal

          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 their last day of study participation

          6. Use of any prescription anticoagulant within 1 month prior to the first dose

          7. Use of prescription and over the counter medications within one week of dosing other
             than the following:

               -  Hormone Replacement Therapy (HRT)

               -  Birth control pills, patches, IUD, rings, injections, or implants (all 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

               -  Proton Pump Inhibitors (PPIs)

               -  Antihistamines

               -  Intermittently used NSAIDS

               -  Acetaminophen if medically necessary (not more than 1000 mg/day)

               -  Exceptions may be allowed on a case by case basis

          8. Subject has a known allergy or sensitivity to zolmitriptan or its derivatives or
             formulations

          9. Subject has a 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) or abnormal nasal exam 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. If, in the opinion of the investigator, the subject is not suitable for the study

         15. Any positive urine drug screen result or alcohol test

         16. Subject currently smokes or is a nicotine a user