A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Study of Elismetrep (K-304) in the Treatment of Migraine: A Range of Doses Will be Evaluated

This is a double-blind, randomized, multicenter, outpatient evaluation of the safety and efficacy of elismetrep as compared to placebo in the treatment of moderate or severe migraine.

Study Overview

• Status: Completed
• Conditions: Acute Migraine
• Intervention / Treatment: Drug: Placebo; Drug: Elismetrep (K-304) Dose Level 1; Drug: Elismetrep (K-304) Dose level 2; Drug: Elismetrep (K-304) Dose level 3; Drug: Elismetrep (K-304) Dose level 4

• Study Type: Interventional
• Enrollment (Actual): 431
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates, LLC (CRA) dba Flourish Research
    • Mobile, Alabama, United States, 36608
      • AMR Mobile
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Wake Research/ Tucson Neuroscience Research
  • California
    • Canoga Park, California, United States, 91303
      • HOPE Clinical Research
    • Encino, California, United States, 91316
      • WR-PRI, LLC (Encino)
    • Huntington Beach, California, United States, 92647
      • Marvel Clinical Research
    • La Mesa, California, United States, 91942
      • Eximia Research - CA
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Newport Beach, California, United States, 92660
      • WR-PRI, LLC (Newport Beach)
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Pomona, California, United States, 91767
      • Empire Clinical Research
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research - Riverside
    • San Diego, California, United States, 92103
      • Artemis Institute For Clinical Research - San Diego
    • San Diego, California, United States, 89109
      • Acclaim Clinical Research
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
    • West Hills, California, United States, 91307
      • Focus Clinical Research
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • CT Clinical Research
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • DelRicht Research
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta - Stockbridge
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center
    • Flossmoor, Illinois, United States, 60422
      • Healthcare Research Network II, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66202
      • Collective Medical Research
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Louisiana
    • Chalmette, Louisiana, United States, 70043
      • Crescent City Headache & Neurology Center
    • New Orleans, Louisiana, United States, 70115
      • DelRicht Research
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain and Neurological Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
  • Mississippi
    • Gulfport, Mississippi, United States, 39503
      • DelRicht Research
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Healthcare Research Network
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • North Las Vegas, Nevada, United States, 89119
      • Las Vegas Clinical Trials
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
    • Manlius, New York, United States, 13104
      • CNY Clinical Research
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates LLC
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center
    • High Point, North Carolina, United States, 27260
      • Peters Medical Research
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • OK Clinical Research, LLC
    • Oklahoma City, Oklahoma, United States, 73102
      • Hightower Clinical
    • Tulsa, Oklahoma, United States, 74133
      • DelRicht Research
    • Yukon, Oklahoma, United States, 73099
      • Tekton Research
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Center for Clinical Research
    • Philadelphia, Pennsylvania, United States, 19114
      • Clinical Research Philadelphia, LLC
    • Scottdale, Pennsylvania, United States, 15683
      • Frontier Clinical Research, LLC
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research, LLC
    • West Chester, Pennsylvania, United States, 19380
      • Atlas-Clinical
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch
    • Knoxville, Tennessee, United States, 37909
      • AMR Knoxville (Formerly NOCCR)
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research
    • Austin, Texas, United States, 78737
      • Donald J Garcia Jr, MD, PA
    • Dallas, Texas, United States, 75251
      • FutureSearch Trials of Dallas, LP
    • Houston, Texas, United States, 77024
      • Victorium Clinical Research LTD CO
    • Splendora, Texas, United States, 77372
      • APD Clinical Research
    • Waxahachie, Texas, United States, 75165
      • ClinPoint Trials
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Frontier Clinical Research, LLC
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Clinical Investigation Specialist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be a male or female, age 18 to 70 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 Conference on Harmonization (IHS) criteria 1.1 and 1.2 and his/her migraines typically last between 4 to 72 hours, if untreated 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 OR
   2. Is a female who is of non-childbearing potential defined by at least 1 of the following criteria:
   3. Postmenopausal (aged >45 years and with a minimum of 12 months of spontaneous amenorrhea with a Screening serum follicle-stimulating hormone (FSH) level in the menopausal range established for the central laboratory.

   4. Post hysterectomy, bilateral oophorectomy or bilateral salpingectomy, based on the subject's recall of their medical history.

      OR

   5. Is a female of reproductive potential and:

   6. agrees to remain abstinent from heterosexual activity*

      *Abstinence can be used as the sole method of contraception if it is in line with the subject'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.

   7. or agrees to use (or have their partner use) a birth control method that is acceptable from the first dose of study drug until the end of trial (EoT) visit. Acceptable methods of birth control are:

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

        • oral
        • intravaginal
        • transdermal

      • progestogen-only hormonal contraception associated with inhibition of ovulation:

        • oral
        • injectable
        • implantable
      • intrauterine device (IUD)
      • intrauterine hormone-releasing system (IUS)
      • bilateral tubal occlusion
      • vasectomised partner
      • sexual abstinence
      • progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
      • male or female condom with or without spermicide
      • cap, diaphragm or sponge with spermicide
      • A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods)

   This condition is waived if the subject is proven to have no child-bearing potential (eg, hysterectomy).

5. Patient voluntarily agrees to participate in the study by giving written informed consent.
6. Patient 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, 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.

Exclusion Criteria:

1. Is a female who is pregnant, breast-feeding or intends to become pregnant during the planned course of the study. Note: Participants must have a negative serum pregnancy test (β-human chorionic gonadotropin (β-hCG)) performed by the central laboratory prior to enrollment in the study and negative urine pregnancy result at the randomization visit.

   Migraine history-related

2. Patient has difficulty distinguishing his/her migraine attacks from tension-type headaches.
3. Patient has a history of predominantly mild migraine attacks or migraines that usually resolve spontaneously in less than two hours.
4. Patient 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. Patient has brainstem (a.k.a. basilar-type) or hemiplegic migraine headache, or retinal migraine.
6. Patient was >50 years old at age of first migraine onset.

7. Patient 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. Any withdrawal of preventive medications for the treatment of migraine should be completed at least 30 days prior to screening.

   Medical history related

8. Patient has, in the opinion of the investigator, other confounding pain syndromes, psychiatric conditions such as uncontrolled major depression, history of psychosis, dementia or significant neurological disorders other than migraine. [Patients who are currently being treated with non-prohibited medication for depression and symptoms are well controlled, in the opinion of the investigator, are eligible to participate in this study].
9. Patient is at imminent risk of self-harm, based on clinical interview and responses on the Columbia Suicidality Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator. Patients must be excluded if they report suicidal ideation with intent, with or without a plan (i.e., Type 4 or 5 on the C-SSRS) in the past 2 months or suicidal behavior in the past 6 months.
10. Has a recent history (within the past 3 years of the screening visit) or current diagnosis or evidence of endocrine, hematological, immunological, renal, respiratory, neurologic, gastrointestinal, biliary, or genitourinary abnormalities or diseases that, per the investigator's judgement, may jeopardize the subject's safety or compliance with the protocol, or otherwise interfere with interpretation of efficacy and/or safety results.
11. Has a history of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed if they have received treatment and follow-up consistent with local standard of care.
12. Patient history with current evidence of uncontrolled, unstable or recently diagnosed cardiovascular disease, such as ischemic heart disease, coronary artery vasospasm, and cerebral ischemia. Patients with Myocardial Infarction (MI), Acute Coronary Syndrome (ACS), percutaneous Coronary Intervention (PCI), cardiac surgery, stroke or transient ischemic attack (TIA) during the 6 months prior to screening.
13. Has a history of human immunodeficiency virus disease.

14. Patient has a history of gastric or small intestinal surgery (including gastric bypass surgery or banding but not including cholecystectomy or appendectomy) or has a disease that causes malabsorption.

    Laboratory, vital sign, and electrocardiogram (ECG) related

15. Has a positive test result at Screening for hepatitis B surface antigen (Ag), hepatitis C virus antibody.
16. Has a screening estimated Glomerular Filtration Rate (eGFR) estimated with the Modification of Diet in Renal Disease (MDRD) equation of <45 ml/min/1.73 m2.
17. Has a screening result for alanine aminotransferase or aspartate aminotransferase (ALT or AST) of >2.0X upper limit of normal (ULN) or total bilirubin >1.5X ULN at the Screening visit. Note: An isolated bilirubin >1.5X ULN is acceptable if bilirubin is fractionated, and direct bilirubin is within the laboratory normal range.
18. Has a corrected QT interval to Fridericia's formula (QTcF) >450 milliseconds (msec) for males and >470 msec for females at screening.

19. Has a mean value for triplicate seated systolic blood pressure >160 mmHg and/or diastolic blood pressure (BP) >95 mmHg measured after at least 5 minutes at rest at the Screening Visit.

    Note: If a subject's BP is exclusionary on the first triplicate assessment at the Screening visit, they may have 1 repeat triplicate BP assessment at that visit after another rest of at least 10 minutes.

    Medication use and substance abuse related

20. Has known history of or suspected abuse of alcohol or recreational drugs at Screening.
21. Has use of soft drugs (such as marijuana or any substances containing tetrahydrocannabinol (THC) or cannabidiol (CBD)) within 3 months prior to Screening, or hard drugs (such as cocaine, illicit narcotics/opiates) within 6 months prior to Screening.
22. Has a positive drug screen at Screening. Note: If benzodiazepines are detected on the drug screen, this is not exclusionary if they are prescribed a benzodiazepine for a therapeutic purpose (e.g. for insomnia) and confirmatory documentation is obtained from the prescribing physician.
23. Is currently in violation of study requirements for prohibited and permissible concomitant medications (not already specified in other criteria) or is anticipated to violate these requirements during study participation.
24. Has any use of prescription opiate medications within 14 days of screening or any anticipated/potential use of opiates during study participation.
25. History of use of ergotamine medications on greater than/equal 10 days per month on a regular basis for greater than/equal 3 months prior to screening.

26. History of non-narcotic analgesic intake on greater than/equal 15 days per month for greater than/equal 3 months prior to screening.

    Other

27. Has known or suspected hypersensitivity to trial product(s) or related products.
28. Has a history of multiple significant and/or any severe allergies (e.g., food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food.
29. Has any surgery scheduled for the duration of the trial.
30. Had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the Screening Visit; has a screening hemoglobin <11.0 g/dL (males) or <10.0 g/dL (females), or has a known hemoglobinopathy (e.g. sickle cell anemia, hemolytic anemia).
31. Has previous participation in this trial. Participation is defined as signed informed consent.
32. Has participated in any clinical trial of an approved or non-approved investigational biological medicinal product (e.g. antibody therapy) within 90 days of Screening or has participated in any clinical trial of an approved or non-approved investigational small molecule medicinal product within 30 days or 5 half-lives (whichever is longer) of Screening.
33. Has any other disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol, or otherwise interfere with interpretation of efficacy and/or safety results.
34. Is an employee or immediate family member (e.g., spouse, parent, child, sibling) of the Sponsor or study site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Administered orally
Experimental: Elismetrep (K-304) Dose level 1	Drug: Elismetrep (K-304) Dose Level 1; Administered orally
Experimental: Elismetrep (K-304) Dose level 2	Drug: Elismetrep (K-304) Dose level 2; Administered orally
Experimental: Elismetrep (K-304) Dose level 3	Drug: Elismetrep (K-304) Dose level 3; Administered orally
Experimental: Elismetrep (K-304) Dose level 4	Drug: Elismetrep (K-304) Dose level 4; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain freedom	Assessed using the number of evaluable subjects that report no pain	2 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from the most bothersome symptom (MBS) (nausea, phonophobia or photophobia)	Assessed using the number of evaluable subjects that report the absence of their MBS	2 hours post-dose
Pain relief	Assessed using the number of evaluable subjects that report a pain level of moderate or severe (responses of 2 or 3 on the 4-point Likert scale) at baseline and then report a pain level of none or mild (response of 0 or 1)	2 hours post-dose
Freedom from Photophobia	Assessed by tabulating the number of subjects that report the absence of photophobia at 2 hours post-dose in the subset of subjects that reported the presence of photophobia at headache baseline	2 hours post-dose
Freedom from Phonophobia	Assessed by tabulating the number of subjects that report the absence of phonophobia at 2 hours post-dose in the subset of subjects that reported the presence of phonophobia at headache baseline	2 hours post-dose
Freedom from Nausea	Assessed by tabulating the number of subjects that report the absence of nausea at 2 hours post-dose in the subset of subjects that reported the presence of nausea at headache baseline	2 hours post-dose
The probability of requiring rescue medication	Assessed using the number of subjects that take rescue medication within 24 hours after administration of study medication	24 hours post-dose
Sustained pain freedom	Assessed using the number of subjects that do not experience any headache pain through the time period of interest	From 2 to 24 hours
Sustained pain relief	Assessed using the number of subjects that do not experience any moderate or severe headache pain through the time period of interest	From 2 to 24 hours
Sustained pain freedom	Assessed using the number of subjects that do not experience any headache pain through the time period of interest	From 2 to 48 hours
Sustained pain relief	Assessed using the number of subjects that do not experience any moderate or severe headache pain through the time period of interest	From 2 to 48 hours
Proportion of participants who experienced 1 or more treatment-emergent AEs		up to 7 days after administration of study medication
Proportion of participants who experienced 1 or more treatment-emergent SAEs		up to 7 days after administration of study medication

Collaborators and Investigators

• Sponsor: Kallyope Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2025
• Primary Completion (Actual): August 11, 2025
• Study Completion (Actual): August 11, 2025

Study Registration Dates

• First Submitted: February 21, 2025
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): February 26, 2025

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: K-304 P001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No