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

A Phase IIa, Multicenter, Randomized, Double-Blind, Placebo-Controlled Crossover Study of K-645 in the Treatment of Multiple Migraine Attacks

This is a multicenter, randomized, double-blind, placebo-controlled, 3-period crossover study to evaluate the safety, tolerability, and efficacy of two dose levels of K-645 in the treatment of patients with acute migraine.

INCLUSION CRITERIA:

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

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

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

4. Meet the following requirements:

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

      • If partner is a non-pregnant female of childbearing potential: To use an appropriate method of contraception, including a condom with spermicidal cream or jelly, from the first dose of study drug until ≥72 hours after the last dose of study drug (i.e. Period 3). A male participant who has had a vasectomy procedure must use a condom but is not required to use spermicidal cream or jelly.
      • If partner is pregnant: To use a condom from the first dose of study drug until ≥72 hours after the last dose of study drug.

      Note: Contraception/condom requirements are waived if partner is NOT of childbearing potential (i.e. is male or is a female who is post-menopausal or surgically sterile [post-hysterectomy or bilateral salpingectomy]).

      • To not donate sperm from the first dose of study drug until ≥ 72 hours after the last dose of study drug.

      OR

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

      • Postmenopausal defined as one of the following: a minimum of 12 months of spontaneous amenorrhea OR a minimum of 6 months of spontaneous amenorrhea with a Screening serum follicle-stimulating hormone (FSH) level >40 mIU/mL OR at least 6 weeks post-bilateral oophorectomy (with or without hysterectomy).
      • Post hysterectomy or bilateral salpingectomy, based on the participant's recall of their medical history.
      • If pre-menopausal, they must agree to not donate eggs from the first dose of 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 after the 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 highly effective**. Acceptable methods of birth control are:

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

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

     • Intrauterine device (IUD)

     • Intrauterine hormone-releasing system (IUS)

     • Bilateral tubal occlusion

     • Vasectomized partner * Abstinence can be used as the sole method of contraception if it is in line with the participant's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ethics committees. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

       • Note: Participants must agree that they will not attempt to become pregnant during the cycles of study drug administration or the menstrual 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 trial procedures and restrictions.

8. Be willing to use their own personal, qualified smartphone to download study-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 the planned course of the study. Note: Female participants of childbearing potential must have a negative serum pregnancy test (beta-human chorionic gonadotropin [beta-hCG]) performed by the central laboratory prior to enrollment in the study and negative 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 usually resolve spontaneously in less than two hours.

4. Has more than 15 headache-days per month or has taken medication for acute headache on 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 has changed during the 3 months prior to Screening (Visit 1) or anticipates any change during the study.

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