MLD10 in the Prevention of Migraine in Adults
Condition: Migraine
MeSH terms: Migraine Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This is a double-blind, placebo-controlled, randomized, multi-center study. Subjects agreeing
      to participate in the study and meet the entry criteria assessed at the screening visit, will
      begin a 28 day baseline period to confirm their diagnosis, as well as establish baseline
      migraine characteristics. During this baseline period, subjects will continue treating their
      migraines as usual, simply recording the information in a daily headache diary. Subjects who,
      after completing the baseline, continue to meet entrance criteria will be eligible to enter
      into the treatment phase and be randomized according to the Clinvest generated randomization
      schedule. Approximately 142 subjects (71 subjects per arm) will be randomized and enter the
      treatment phase receiving MLD10 or placebo in a 1:1 design at 6 United States sites. Diary
      assessments will collect study medication adherence, pain severity, headache symptoms, acute
      medication usage, and unusual symptoms. Serum samples will be collected and analyzed for
      ionized magnesium, electrolytes, and creatinine.
    

Detailed description: 
      This is a multi-center, double-blind, randomized, placebo-controlled, parallel study of MLD10
      for the prevention of migraine headache. The study population will consist of approximately
      142 male and female subjects between 18 and 65 years of age with frequent episodic migraine
      as defined by International Classification of Headache Disorders-3beta criteria. Two MLD10
      (243 mg (milligrams) of elemental magnesium) or placebo caplets will be taken twice daily for
      a total daily dose of 486 mg.

      VISIT 1 - SCREENING

      The following will be completed at Visit 1:

        1. Obtain written Informed Consent. The informed consent will be obtained in accordance
           with Good Clinical Practices (GCP) and all applicable regulatory requirements from each
           subject prior to participation in the study.

        2. Verify Inclusion/Exclusion Criteria. Subjects will meet all the inclusion and none of
           the exclusion criteria.

        3. Obtain demographics (race, ethnicity, sex, date of birth)

        4. Obtain medical, medication, and headache history. Data collected will include medical
           history and diagnoses, age at onset of migraine and other pertinent migraine/headache
           history, history of acute and prophylactic headache medications within the past 30 days,
           and history of other recent/concomitant medications.

        5. Obtain date of last menstrual cycle and perform urine pregnancy test, if appropriate.
           Results of the pregnancy test must be negative to continue in study.

        6. Perform physical and neurological examinations.

        7. Measure vital signs (height, weight, resting heart rate, and blood pressure).

        8. Review Baseline Headache Diary. Subjects will be instructed to complete a daily online
           headache diary. Assessments to be captured are start/stop time, severity, associated
           symptoms, use of rescue medications, and unusual symptoms.

        9. Administer Columbia-Suicide Severity Rating Scale (C-SSRS).

       10. Schedule Visit 2.

      VISIT 2 - RANDOMIZATION

        1. Verify Inclusion/Exclusion Criteria. Subjects must continue to meet all inclusion
           (including ≥ 3 days of migraine during baseline) and none of the exclusion criteria.

        2. Perform urine pregnancy test, if appropriate. Results of the pregnancy test must be
           negative to continue in study.

        3. Measure vital signs (weight, resting heart rate, and blood pressure).

        4. Record any changes to concomitant medications.

        5. Record any Serious Adverse Events (SAE) since signing the Informed Consent.

        6. Review Baseline Headache Diary for completeness and continuing eligibility.

        7. Randomize subject

        8. Review Month 1 Headache Diary instructions (same instructions as those discussed for
           Baseline Headache Diary).

        9. Dispense Month 1 study medication. Subjects will be instructed how to take study
           medication, prohibited medications/foods, dosage limitations of study medication, and
           storage requirements. Subjects will be instructed to return all used/partially
           used/unused study medication at next office visit and medications reconciliation will be
           performed to ensure a compliance of at least 80%. Subjects not complying at an 80% level
           will be withdrawn, unless otherwise approved by the Sponsor and/or Clinvest. (Estimated
           to be < 10%)

       10. Administer C-SSRS.

       11. Administer MIDAS.

       12. Collect serum samples for electrolytes, creatinine, and ionized Mg.

       13. Schedule Visit 3.

      VISIT 3 - END OF TREATMENT PERIOD MONTH 1

        1. Record any changes to concomitant medications.

        2. Record any Non-Serious Adverse Events (NSAE) and/or SAEs.

        3. Perform urine pregnancy test, if appropriate. Results of the pregnancy test must be
           negative to continue in study.

        4. Measure vital signs (weight, resting heart rate, and blood pressure).

        5. Review Month 1 Headache Diary for completeness.

        6. Review instructions for Month 2 Headache Diary (same instructions as those discussed for
           Month 1 Headache Diary).

        7. Collect Month 1 unused study medication and used packaging. Confirm 85% compliance of
           medication usage per study protocol.

        8. Dispense Month 2 study medication and review the dosage limitations of study medication,
           storage requirements, and to return all used/partially used/unused study medication at
           next office visit.

        9. Perform drug accountability.

       10. Administer C-SSRS.

       11. Collect serum samples for electrolytes, creatinine, and ionized Mg.

       12. Schedule Visit 4.

      VISIT 4 - END OF TREATMENT PERIOD MONTH 2

        1. Record any changes to concomitant medications.

        2. Record any NSAEs/SAEs.

        3. Perform urine pregnancy test, if appropriate. Results of the pregnancy test must be
           negative to continue in study.

        4. Measure vital signs (weight, resting heart rate, and blood pressure).

        5. Review Month 2 Headache Diary for completeness.

        6. Review instructions for Month 3 Headache Diary (same instructions as those discussed for
           Month 2 Headache Diary).

        7. Collect Month 2 unused study medication and used packaging. Confirm 85% compliance for
           medication usage per study protocol.

        8. Dispense Month 3 study medication and review the dosage limitations of study medication,
           storage requirements, and to return all used/partially used/unused study medication at
           next office visit.

        9. Perform drug accountability.

       10. Administer C-SSRS.

       11. Collect serum samples for electrolytes, creatinine, and ionized Mg.

       12. Schedule Visit 5.

      VISIT 5 - END OF TREATMENT PERIOD MONTH 3

        1. Record any changes to concomitant medications.

        2. Record any NSAEs/SAEs.

        3. Perform urine pregnancy test, if appropriate.

        4. Measure vital signs (weight, resting heart rate, and blood pressure)

        5. Perform physical/neurological examinations.

        6. Collect Month 4 unused study medication and used packaging.

        7. Perform drug accountability.

        8. Administer SGIC & complete PGIC.

        9. Administer MIDAS.

       10. Administer C-SSRS.

       11. Collect serum samples for electrolytes, creatinine, and ionized Mg.

       12. Exit subject.
    

Intervention name(s): MLD10; Placebo
Intervention type(s): Drug; Drug
Other intervention name(s): elemental magnesium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention