A Study of K-645 in the Treatment of Multiple Migraine Attacks

INCLUSION CRITERIA:

1. Be a male or female, age 18 to 65 years, inclusive, at the time of signing informedconsent.

2. Patient has greater than a one-year history of migraine with or without aura asdefined by International Headache Society (IHS) criteria 1.1 and 1.2 and his/hermigraines typically last between 4 to 72 hours, if untreated (refer to InternationalClassification of Headache Disorders [ICHD] III Attachment for IHS migrainedefinitions) as documented in the patient's medical records from his/her treatingphysician and confirmed by the investigator.

3. Patient has had ≥2 and ≤10 moderate or severe migraine attacks per month in each ofthe two months prior to Screening (Visit 1).

4. Meet the following requirements:

5. Is a male who agrees to all of the following:

• If partner is a non-pregnant female of childbearing potential: To use anappropriate method of contraception, including a condom with spermicidalcream or jelly, from the first dose of study drug until ≥72 hours afterthe last dose of study drug (i.e. Period 3). A male participant who hashad a vasectomy procedure must use a condom but is not required to usespermicidal cream or jelly.
• If partner is pregnant: To use a condom from the first dose of study druguntil ≥72 hours after the last dose of study drug.Note: Contraception/condom requirements are waived if partner is NOT ofchildbearing potential (i.e. is male or is a female who is post-menopausal orsurgically sterile [post-hysterectomy or bilateral salpingectomy]).
• To not donate sperm from the first dose of study drug until ≥ 72 hoursafter the last dose of study drug.OR

2. Is a female who is of non-childbearing potential defined by at least 1 of thefollowing criteria:

• Postmenopausal defined as one of the following: a minimum of 12 months ofspontaneous amenorrhea OR a minimum of 6 months of spontaneous amenorrheawith a Screening serum follicle-stimulating hormone (FSH) level >40 mIU/mLOR at least 6 weeks post-bilateral oophorectomy (with or withouthysterectomy).

• Post hysterectomy or bilateral salpingectomy, based on the participant'srecall of their medical history.

• If pre-menopausal, they must agree to not donate eggs from the first doseof study drug until 30 days after the last dose study drug. OR c. Is a female of reproductive potential and:

• agrees to not donate eggs from the first dose of study drug until 30 days afterthe last dose study drug. AND

• agrees to remain abstinent from heterosexual activity*,** or

• agrees to use (or have their partner use) a birth control method that is highlyeffective**. Acceptable methods of birth control are:

• Combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation

• Progestogen-only contraception (e.g. oral, injectable, implant) associatedwith inhibition of ovulation

• Intrauterine device (IUD)

• Intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion

• Vasectomized partner * Abstinence can be used as the sole method ofcontraception if it is in line with the participant's preferred and usuallifestyle and if considered acceptable by local regulatory agencies andethics committees. Periodic abstinence (e.g., calendar, ovulation,sympto-thermal, post-ovulation methods, etc.) and withdrawal are notacceptable methods of contraception.

• Note: Participants must agree that they will not attempt to becomepregnant during the cycles of study drug administration or themenstrual cycle following the last dose of study medication.

5. Voluntarily agrees to participate in the study by giving written informed consent.

6. Is able to read, understand, and complete the study questionnaires and diary.

7. Be willing and able to comply with the study schedule of visits and all trialprocedures and restrictions.

8. Be willing to use their own personal, qualified smartphone to downloadstudy-specific eDiary applications for use during the study.

KEY EXCLUSION CRITERIA:

1. Is a female who is pregnant, breast-feeding or intends to become pregnant during theplanned course of the study. Note: Female participants of childbearing potentialmust have a negative serum pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) performed by the central laboratory prior to enrollment in the study andnegative urine pregnancy result at the randomization visit. Migraine history-related exclusion criteria

2. Has difficulty distinguishing his/her migraine attacks from tension-type headaches.

3. Has a history of predominantly mild migraine attacks or migraines that usuallyresolve spontaneously in less than two hours.

4. Has more than 15 headache-days per month or has taken medication for acute headacheon more than 10 days per month in any of the three months prior to Screening (Visit 1).

5. Has brainstem (also known as [a.k.a.] basilar-type) or hemiplegic migraine headache,or retinal migraine.

6. Was >50 years old at age of first migraine onset.

7. Is taking migraine prophylactic medication where the prescribed daily dose haschanged during the 3 months prior to Screening (Visit 1) or anticipates any changeduring the study.

8. Stopped preventive migraine medication(s) within 30 days prior to Screening forsmall molecules or 90 days for antibodies.