Migraine
Conditions
Brief summary
This is a double-blind, randomized, multicenter, outpatient evaluation of the safety and efficacy of elismetrep, as compared with placebo, in the treatment of moderate or severe of migraine.
Interventions
DRUGElismetrep
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Kallyope Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1\. Be a male or female, age 18 to 75 years, inclusive, at the time of signing informed consent. 2\. Has greater than a one-year history of migraine with or without aura as defined by International Headache Society 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 or with pharmacy records confirming use of a migraine-specific medication (e.g. triptan, gepant, ditan) for \> 1 year, and confirmed by the investigator. 3. Has had ≥2 and ≤10 moderate or severe migraine attacks per month in each of the 2 months prior to screening (Visit 1). 4. Meet the following requirements: a. Is a male OR b. Is a female who is of non-childbearing potential defined by at least one of the following criteria: i. Postmenopausal as defined by one of the following: 1. A minimum of 12 months of spontaneous amenorrhea or 2. A minimum of 6 months of spontaneous amenorrhea with a screening serum follicle-stimulating hormone level \> 40 mIU/mL or 3. At least 6 weeks post bilateral oophorectomy (with or without hysterectomy). OR ii. Post hysterectomy or bilateral salpingectomy, based on the subject's recall of their medical history OR c. Is a female of reproductive potential and: i. Agrees to remain abstinent from heterosexual activity\* OR ii. 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 Study visit. Acceptable methods of birth control are: 1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal). 2. Progestogen-only hormonal contraception associated with inhibition of ovulation (oral; injectable; or implantable). 3. Intrauterine device (IUD); 4. Intrauterine hormone-releasing system (IUS); 5. Bilateral tubal occlusion; 6. Vasectomized partner; 7. Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action; 8. Male or female condom with or without spermicide; 9. Cap, diaphragm or sponge with spermicide; 10. A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods). \* 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. 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 eDiary. 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
Patients are excluded from the trial if any of the following criteria apply: 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 child-bearing potential must have a negative serum pregnancy test (β-human chorionic gonadotropin) performed by the central laboratory prior to enrollment in the study and negative urine pregnancy result at the randomization visit. Migraine history-related 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 2 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 3 months prior to screening (Visit 1). 5. Has brainstem (also known as 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 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. 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. 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 (including Sjogren's syndrome), renal, respiratory, neurologic, gastrointestinal, biliary, or genitourinary abnormalities or diseases or hepatic impairment 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. Has a 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, acute coronary syndrome, percutaneous coronary intervention, cardiac surgery, stroke or transient ischemic attack during the 6 months prior to screening. 13. Has a history of human immunodeficiency virus disease. 14. 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 related 15. Has a positive test result at screening for hepatitis B surface antigen, hepatitis C virus antibody. 16. Has a screening estimated glomerular filtration rate estimated with the Modification of Diet in Renal Disease (MDRD) equation of \<30 mL/min/1.73 m2. 17. Has a screening result for alanine aminotransferase or aspartate aminotransferase of \>2.0 X upper limit of normal (ULN) or total bilirubin \>1.5 X ULN at the Screening visit. Note: An isolated bilirubin \>1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin is within the laboratory normal range. 18. Has a mean value for triplicate corrected QT interval to Fridericia's formula (QTcF) \>450 ms for males and \>470 ms for females at screening. 19. Has a mean value for triplicate seated systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>95 mmHg measured after at least 5 minutes at rest at the Screening Visit. Note: If a participant's blood pressure is exclusionary on the first triplicate assessment at the Screening Visit, they may have one repeat triplicate blood pressure 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: 1. 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. 2. If amphetamines are detected on the drug screen, this is not exclusionary if the participant is taking a stimulant medication for a therapeutic purpose (e.g., Adderall for attention deficit hyperactivity disorder), confirmatory documentation is obtained from the prescribing physician, and the stimulant medication in question is known to be detected as amphetamine on the drug screen being used. 23. Is currently in violation of study requirements for prohibited and permissible concomitant medications or treatments (not already specified in other criteria) or is anticipated to violate these requirements during study participation (detailed in the protocol). 24. Has any use of prescription opiate medications within 14 days of screening or any anticipated/potential use of opiates during study participation. 25. Has a history of use of ergotamine medications ≥10 days per month on a regular basis for ≥3 months prior to screening. 26. Has a history of non-narcotic analgesic intake ≥15 days per month for ≥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. 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 or ever signed an informed consent for Study K-304 P003. Note: Patients may not be screened at more than one trial site for this study. 33. Has any other disorder, unwillingness or inability, not covered by any of the other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain freedom at 2 hours post-dose | Two hours post-dose | Percentage of subjects who report no pain at 2 hours post-dose. Pain will be measured on a 4-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe). |
| Freedom from most bothersome symptoms (MBS) at 2 hours post-dose | Two hours post-dose | Percentage of subjects who report absence of their MBS (nausea, phonophobia, or photophobia) at 2 hours post-dose. MBS will be measured using a binary scale (0=absent, 1=present). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain relief at 2 hours post-dose | Two hours post-dose | Percentage of subjects who report a pain level of moderate of severe (responses of 2 or 3 on the 4-point Likert scale) at baseline and then report a pain level of none or mild (responses of 0 or 1 on the 4-point Likert scale) at 2 hours post-dose. |
| Sustained pain freedom from 2 to 24 hours post-dose | From 2 to 24 hours post-dose | Percentage of subjects who do not use any rescue medication, do not experience any headache pain through the time period of interest, and do not have missing pain data at 2 or 24 hours post-dose. |
| Sustained pain freedom from 2 to 48 hours post-dose | From 2 to 48 hours post-dose | Percentage of subjects who do not use any rescue medication, do not experience any headache pain through the time period of interest, and do not have missing pain data at 2, 24, or 48 hours post-dose. |
| Sustained pain relief from 2 to 24 hours post-dose | From 2 to 24 hours post-dose | Percentage of subjects who do not use any rescue medications, do not experience any moderate or severe headache pain through the time period of interest, and do not have missing pain data at 2 or 24 hours post-dose. |
| Sustained pain relief from 2 to 48 hours post-dose | From 2 to 48 hours post-dose | Percentage of participants that do not use any rescue medications, do not experience any moderate or severe headache pain through the time period of interest, and do not have missing pain data at 2, 24, or 48 hours post-dose. |
| Freedom from functional disability at 2 hours post-dose | Two hours post-dose | Percentage of subjects who self-report as being able to function normally on the functional disability scale in the subset of subjects who reported any level of disability at baseline. The scale has a 4-point numeric rating: normal (0); mildly impaired (1); moderately impaired (2); severely impaired, requires bedrest (3). |
| Proportion requiring rescue medication within 24 hours post-dose | Within 24 hours post-dose | Percentage of subjects that take rescue medication within 24 hours post-dose. |
| Freedom from photophobia at 2 hours post-dose | Two hours post-dose | Percentage of subjects who report the absence of photophobia at 2 hours post-dose in the subset of subjects who reported the presence of photophobia at baseline. |
| Freedom from phonophobia at 2 hours post-dose | Two hours post-dose | Percentage of subjects who report the absence of phonophobia at 2 hours post-dose in the subset of subjects who reported the presence of phonophobia at baseline. |
| Freedom from nausea at 2 hours post-dose | Two hours post-dose | Percentage of subjects who report the absence of nausea at 2 hours post-dose in the subset of subjects who reported the presence of nausea at baseline. |
| Pain relapse from 2 to 48 hours post-dose | From 2 to 48 hours post-dose | Percentage of subjects who are pain free at 2 hours post-dose and have (a) mild, moderate, or severe pain (response of 1, 2, or 3 on the 4-point Likert scale) at any time point after 2 hours post-dose, or (b) missing pain data at 24 hours or 48 hours after 2 hours post-dose, or (c) intervening rescue medication use at or before 48 hours post-dose. |
| Percentage of participants who experience one or more treatment-emergent adverse events (AEs) | Up to 8 days post-dose | — |
| Percentage of participants who experience one or more treatment-emergent serious adverse events (SAEs) | Up to 8 days post-dose | — |
Countries
United States
Contacts
CONTACTMichael Crutchlow Kallyope Clinical Director and Medical Monitor, MD
Outcome results
None listed