MLD10 in the Prevention of Migraine in Adults
MLD10 in the Prevention of Migraine in Adults
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.
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.
Inclusion Criteria:

 1. male or female, in otherwise good health, 18 to 65 years of age.

 2. history of frequent episodic migraine (3-14 migraine days per month) (with or without
 aura) according to the International Classification of Headache Disorders-3beta for at
 least 3 months.

 3. onset of migraine before age 50.

 4. stable history of migraine at least 3 months prior to screening.

 5. not currently taking a migraine preventive or has been taking preventive for at least
 30 days prior to screening and agrees to not start, stop, or change medication and/or
 dosage during the study period.

 6. if female of childbearing potential, has a negative urine pregnancy test at Visits 1-5
 and uses, or agrees to use, for the duration of the study, a medically acceptable form
 of contraception as listed:

 -  complete abstinence from intercourse from 2 weeks prior to administration of
 study drug, throughout the study, and for 7 days after completion or premature
 discontinuation from the study; surgically sterile (hysterectomy or tubal
 ligation or otherwise incapable of pregnancy); sterilization of male partner when
 in a monogamous relationship; intrauterine device with published data showing
 lowest expected failure rate is less than 1% per year; double barrier method
 (i.e., 2 physical barriers OR 1 physical barrier plus spermicide) for a least 1
 month prior to Visit 1 and throughout study; or hormonal contraceptives for at
 least 3 months prior to Visit 1 and throughout study.

 7. completion of online diary must be ≥ 80% compliance, unless otherwise approved by the
 Sponsor and/or Clinvest.

 Exclusion Criteria:

 1. unable to understand the study requirements, the informed consent, or complete
 headache records as required per protocol.

 2. pregnant, actively trying to become pregnant, or breast-feeding.

 3. diagnosed with International Classification of Headache Disorders-3beta criteria for
 Chronic Migraine within 3 months prior to screening, at the time of screening, and/or
 during the baseline period.

 4. experienced the following migraine variants: basilar migraine, aura without headache,
 familial hemiplegic migraine, complicated migraine, ophthalmoplegic migraine and
 retinal migraine within the last year.

 5. history of medication overuse headache (MOH) (Appendix II) in the 3 months prior to
 study enrollment or during the baseline phase.

 6. history of medication overuse (MO) of ergotamines, triptans, opioids, analgesics,
 NSAIDS and combination therapies, as defined by ICHD-3beta criteria and/or MO during
 baseline period.

 7. history of substance abuse and/or dependence, in the opinion of the Investigator.

 8. history of impaired renal function that, in the investigator's opinion,
 contraindicates participation in this study.

 9. unstable neurological condition or a significantly abnormal neurological examination
 with focal signs or signs of increased intracranial pressure.

 10. suffers from a serious illness, or an unstable medical condition, one that could
 require hospitalization, or could increase the risk of adverse events.

 11. has significant risk of suicide, defined as a "yes" answer to any of the following
 questions on the Columbia-Suicide Severity Rating Scale (C-SSRS), either at the
 screening visit (when assessing the prior 12 months) or at visit 2 (when assessing
 time since the screening visit):

 1. Questions 4 or 5 on the suicidal ideation section

 2. Any question on any item in the suicidal behavior section

 12. any psychiatric disorder with psychotic features, and/or any other psychiatric
 disorder not stable or well controlled, that would interfere in their ability to
 complete study activities.

 13. hypersensitivity, intolerance, or contraindication to the use of magnesium L-lactate
 dehydrate or any of its components.

 14. received any investigational agents within 30 days prior to Visit 1.

 15. plans to participate in another clinical study at any time during this study.